PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 31925328-3 2020 Using BCR-ABL as a case study, we successfully recaptured the clinically observed mutations that confer resistance imatinib, nilotinib, dasatinib, bosutinib, and ponatinib. ponatinib 162-171 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 6-13 33419251-4 2020 Here, we presented a 77-year-old male with a diagnosis of Ph positive ALL resistant to ponatinib and carrying a rare threonine to leucine (T315L) mutation on BCR-ABL1 gene. ponatinib 87-96 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 162-166 33460055-0 2020 Dynamic evolution of ponatinib-resistant mutations in BCR-ABL1-positive leukaemias revealed by next-generation sequencing. ponatinib 21-30 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 58-62 32175644-0 2020 Renovascular hypertension from the BCR-ABL tyrosine kinase inhibitor ponatinib. ponatinib 69-78 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 35-42 32095692-1 2020 Ponatinib is a multikinase inhibitor that is used to treat chronic myeloid leukemia patients harboring mutated ABL1(T315I) kinase. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 111-115 32095692-6 2020 A nicotinamide analogue of ponatinib, HSN748, retains activity against FLT3, ABL1, RET, and PDGFRalpha/beta but loses activity against c-Src and P38alpha. ponatinib 27-36 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 77-81 31115499-3 2019 PF-114, a derivative of the third generation BCR-ABL inhibitor ponatinib, demonstrated a high inhibitory activity against wild-type and mutant BCR-ABL forms, such as the clinically important T315I. ponatinib 63-72 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 45-52 32829325-1 2020 INTRODUCTION: Ponatinib (PNT) is a tyrosine kinase inhibitor approved for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), or chronic myeloid leukemia, resistant or intolerant to other tyrosine kinase inhibitor or showing T315I mutation of BCR-ABL. ponatinib 14-23 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 288-295 30661457-0 2020 How does the novel T315L mutation of breakpoint cluster region-abelson (BCR-ABL) kinase confer resistance to ponatinib: a comparative molecular dynamics simulation study. ponatinib 109-118 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 37-70 30661457-0 2020 How does the novel T315L mutation of breakpoint cluster region-abelson (BCR-ABL) kinase confer resistance to ponatinib: a comparative molecular dynamics simulation study. ponatinib 109-118 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 72-79 30661457-5 2020 The latest third-generation TKIs, ponatinib, can tackle most abnormal BCR-ABL kinases, including the T315I mutant that is resistant to first- and second-generations TKIs such as imatinib. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 70-77 30661457-7 2020 Here, using molecular dynamics (MD) simulations, we explored into the detailed interactions between ponatinib and BCR-ABL in the wild-type (WT), T315I, and T315L systems. ponatinib 100-109 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 114-121 30661457-9 2020 Binding free energy analysis unveiled that the affinity of ponatinib to BCR-ABL decreased upon T315L mutation, which resulted in its unfavorable binding and drug resistance. ponatinib 59-68 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 72-79 31510844-0 2019 Ponatinib use in two pediatric patients with relapsed Ph + ALL with ABL1 kinase domain mutations. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 68-72 30580670-2 2019 Ponatinib, an oral drug, was discovered as an efficient BCR-ABL inhibitor by addressing imatinib drug resistance arising due to the point mutations at its active sites. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 56-63 30580670-3 2019 In this study, 44 BCR-ABL kinase inhibitors, which are derivatives of ponatinib, were used to develop a robust two-dimensional quantitative structure-activity relationship (2D-QSAR) and 3D-Pharmacophore models by dividing dataset into 32 training sets and 12 test set molecules. ponatinib 70-79 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 18-25 31115499-3 2019 PF-114, a derivative of the third generation BCR-ABL inhibitor ponatinib, demonstrated a high inhibitory activity against wild-type and mutant BCR-ABL forms, such as the clinically important T315I. ponatinib 63-72 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 143-150 29608815-5 2018 Ponatinib (AP24534) is currently the only approved CML drug that is active against the ABL1(T315I) mutation. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 87-91 30705592-3 2019 Iclusig (ponatinib, previously known as AP24534) is an orally active multi-tyrosine kinase inhibitor and is currently approved by the US Food and Drug Administration for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, specifically targeting the BCR-ABL gene mutation, T315I. ponatinib 0-7 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 304-311 30705592-3 2019 Iclusig (ponatinib, previously known as AP24534) is an orally active multi-tyrosine kinase inhibitor and is currently approved by the US Food and Drug Administration for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, specifically targeting the BCR-ABL gene mutation, T315I. ponatinib 10-19 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 304-311 30705592-3 2019 Iclusig (ponatinib, previously known as AP24534) is an orally active multi-tyrosine kinase inhibitor and is currently approved by the US Food and Drug Administration for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, specifically targeting the BCR-ABL gene mutation, T315I. ponatinib 41-48 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 304-311 30217442-4 2018 Treatment of CML-derived K562 cells with BCR-ABL tyrosine kinase inhibitors, including imatinib, dasatinib, nilotinib and ponatinib, prevented activation of eIF2alpha kinases, protein kinase-like endoplasmic reticulum kinase (PERK) and general control nonderepressible 2, and downstream ATF4 induction during metabolic stress. ponatinib 122-131 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 41-48 29675611-9 2018 Ponatinib seems a valid second-line treatment option for chronic phase CML, in particular for patients who failed a front-line second-generation TKI due to BCR-ABL-independent mechanisms of resistance. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 156-163 30024740-6 2018 Moreover, the inactivation of both Abl and Src by the inhibitor imatinib, dasatinib, and ponatinib was simultaneously traced, giving a whole picture of the competition behavior between the kinases for binding therapeutic molecules. ponatinib 89-98 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 35-38 30238007-1 2018 Ponatinib is a multi-targeted third generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML) patients harboring the Abelson (Abl)-breakpoint cluster region (Bcr) T315I mutation. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 158-165 30238007-1 2018 Ponatinib is a multi-targeted third generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML) patients harboring the Abelson (Abl)-breakpoint cluster region (Bcr) T315I mutation. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 167-170 29608815-6 2018 However, ponatinib has severe cardiovascular toxicities; hence, there have been efforts to find safer CML drugs that work against ABL1 secondary mutations. ponatinib 9-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 130-134 29050692-3 2017 In particular, ponatinib, a potent pan-BCR-ABL TKI capable of overcoming the T315I mutation, holds significant promise in the treatment of Ph+ ALL, although the potential cardiovascular toxicity of this agent remains a concern. ponatinib 15-24 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 39-46 29675955-7 2018 Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. ponatinib 75-84 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 37-41 29899872-2 2018 Ponatinib blocks a variety of tyrosine kinases including ABL and fibroblast growth factor receptor (FGFR), and the BET bromodomain (BRD) antagonists JQ1 and dBET1 impede MYC oncogene expression. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 57-60 29434033-4 2018 Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation, PDGFRBC843G , which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib. ponatinib 245-254 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 189-192 29165716-2 2018 Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. ponatinib 9-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 80-87 29165716-2 2018 Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. ponatinib 9-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 199-206 29165716-4 2018 Methods: Two CML cell lines with acquired BCR-ABL-independent resistance were generated following culture in ponatinib. ponatinib 109-118 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 42-49 29165716-9 2018 Results: We show that ponatinib-resistant CML cells can acquire BCR-ABL-independent resistance mediated through alternative activation of mTOR. ponatinib 22-31 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 64-71 31249931-2 2018 Second- (dasatinib, nilotinib, and bosutinib) and third-generation (ponatinib) TKIs have been developed to be effective against BCR-ABL mutations making imatinib less effective. ponatinib 68-77 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 128-135 29358661-3 2018 The third generation TKI ponatinib is the only effective TKI to treat CML patients harboring T315I-BCR-ABL mutation, but with high rate of major arterial thrombotic events. ponatinib 25-34 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 99-106 30069627-10 2018 In conclusion, ponatinib has proved to be a powerful BCR-ABL inhibitor, which exhibits clinical activity both in BCR-ABL wild-type and mutant CML, including the pan-resistant T315I mutation. ponatinib 15-24 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 53-60 30069627-10 2018 In conclusion, ponatinib has proved to be a powerful BCR-ABL inhibitor, which exhibits clinical activity both in BCR-ABL wild-type and mutant CML, including the pan-resistant T315I mutation. ponatinib 15-24 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 113-120 27696211-1 2017 Five clinically approved BCR-ABL1-targeted tyrosine kinase inhibitors (bosutinib, dasatinib, imatinib, nilotinib, and ponatinib) used for treating chronic myelogenous leukemia have been studied in a neonatal rat myocyte model for their relative ability to induce myocyte damage. ponatinib 118-127 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 29-33 28427224-4 2017 The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). ponatinib 48-57 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 75-78 28278078-2 2017 In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. ponatinib 164-173 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 26-33 27166836-10 2016 Ponatinib inhibited phosphorylation not only of BCR-ABL but also of downstream signal transducer and activator of transcription 5, protein kinase B, and ERK1/2 in both K562/IM-R1 and Ba/F3/T315I, and the addition of panobinostat to ponatinib further inhibited these phosphorylations. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 48-55 28184964-1 2017 PURPOSE: Ponatinib is a novel tyrosine kinase inhibitor (TKI) specifically designed to inhibit native and mutated BCR-ABL. ponatinib 9-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 114-121 27761606-0 2017 BCR-ABL-positive acute myeloid leukemia: About one case treated with ponatinib. ponatinib 69-78 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 0-7 27864605-0 2017 Erratum to: BCR-ABL-positive acute myeloid leukemia: About one case treated with ponatinib. ponatinib 81-90 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 12-19 27852118-1 2017 BACKGROUND: A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. ponatinib 147-156 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 79-86 26479578-6 2016 Baustinib, Nilotinib, Dasatinib, Ponatinib, Bafetinib, etc., which can able to combat against mutated domain of ABL tyrosine kinase protein. ponatinib 33-42 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 112-115 27166836-11 2016 In conclusion, panobinostat enhanced the cytotoxicity of ponatinib towards IM-resistant CML cells including those with T315I-mutated BCR-ABL. ponatinib 57-66 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 133-140 25894969-8 2015 One patient with lymphoid BC/Ph+ ALL who harbored a T315I ABL mutation and was treated with ponatinib was found to have developed a newly acquired V216M TP53 mutation (12% of transcripts) when becoming resistant to ponatinib. ponatinib 92-101 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 58-61 27044711-1 2016 Chronic myeloid leukemia (CML) patients who relapse on imatinib due to acquired ABL1 kinase domain mutations are successfully treated with second-generation ABL1-tyrosine kinase inhibitors (ABL-TKIs) such as dasatinib, nilotinib or ponatinib. ponatinib 232-241 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 80-84 27044711-1 2016 Chronic myeloid leukemia (CML) patients who relapse on imatinib due to acquired ABL1 kinase domain mutations are successfully treated with second-generation ABL1-tyrosine kinase inhibitors (ABL-TKIs) such as dasatinib, nilotinib or ponatinib. ponatinib 232-241 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 157-161 26864341-5 2016 Conversely, allosteric stimulation of ABL1 kinase activity enhanced the antileukemia effect of ABL1 tyrosine kinase inhibitors (imatinib and ponatinib) in human and murine leukemias expressing BCR-ABL1, TEL-ABL1, and NUP214-ABL1. ponatinib 141-150 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 38-42 26864341-5 2016 Conversely, allosteric stimulation of ABL1 kinase activity enhanced the antileukemia effect of ABL1 tyrosine kinase inhibitors (imatinib and ponatinib) in human and murine leukemias expressing BCR-ABL1, TEL-ABL1, and NUP214-ABL1. ponatinib 141-150 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 95-99 26607600-9 2016 Moreover, the BCR/ABL1 inhibitors nilotinib and ponatinib were found to decrease STAT5 activity and CD25 expression in KU812 cells and primary CML LSCs. ponatinib 48-57 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 18-22 26562217-3 2015 Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-Abl(T315I) by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. ponatinib 42-51 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 205-212 26458439-10 2015 Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harboring T315I. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 25-28 26458439-10 2015 Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harboring T315I. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 82-89 25801024-2 2015 In the current work, we report that the Bcr-Abl inhibitor and anti-leukemia agent ponatinib is also a first-in-class dual inhibitor of RIPK1 and RIPK3. ponatinib 82-91 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 40-47 25686603-4 2015 The BCR-ABL1 kinase domain gatekeeper mutation Thr315Ile (T315I) confers resistance to all approved ABL1 inhibitors except ponatinib, which has toxicity limitations. ponatinib 123-132 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 8-12 26195136-1 2015 A series of pyrimidine alkynyl derivatives were designed and synthesized as new Bcr-Abl inhibitors by hybriding the structural moieties from GNF-7, ponatinib and nilotinib. ponatinib 148-157 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 80-87 25894969-9 2015 Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-34 25894969-9 2015 Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 188-191 25894969-9 2015 Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. ponatinib 78-87 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-34 25894969-9 2015 Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. ponatinib 120-129 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-34 25894969-9 2015 Ponatinib led to a decrease of ABL T315I positive transcripts from 47% before ponatinib treatment to 16% at the time of ponatinib resistance in this patient, suggesting that both TP53 and ABL mutations were present in the same clone and that the newly acquired TP53 mutation might have caused ponatinib resistance in this patient. ponatinib 120-129 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-34 25527332-0 2015 The BCR-ABL inhibitor ponatinib inhibits platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling, platelet activation and aggregate formation under shear. ponatinib 22-31 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 4-11 25304212-1 2015 Ponatinib, a multi-targeted TKI and potent pan-ABL inhibitor, approved for the treatment of Ph + ALL and CML, was temporarily withdrawn from the U.S. market due to severe vascular adverse events. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 47-50 25465127-2 2014 Despite a high level of sequence homology in the ATP-binding site, the majority of reported inhibitors are selective for the FGFR1-3 isoforms and display much reduced potency toward FGFR4, an exception being the Bcr-Abl inhibitor ponatinib. ponatinib 230-239 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 212-219 25382104-4 2014 Drugs that are currently available, such as imatinib and ponatinib, were also docked against BCR-ABL protein to set a cutoff value for our screening. ponatinib 57-66 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 93-100 25527332-9 2015 As our results indicate that pobatinib inhibits platelet function, the adverse cardiovascular events observed in patients taking ponatinib may be the result of the effect of ponatinib on other organs or cell types, or disease-specific processes, such as BCR-ABL+cells undergoing apoptosis in response to chemotherapy, or drug-induced adverse effects on the integrity of the vascular endothelium in ponatinib-treated patients. ponatinib 129-138 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 254-261 25536607-1 2014 PURPOSE: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. ponatinib 9-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 124-131 25536607-1 2014 PURPOSE: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. ponatinib 150-159 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 124-131 24768818-8 2014 Whereas imatinib and ponatinib bind potently to both the DDR and ABL kinases, the hydrophobic interactions of the ABL P-loop appear poorly satisfied by DDR1-IN-1 suggesting a structural basis for its DDR1 selectivity. ponatinib 21-30 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 65-68 24481648-4 2014 Ponatinib, a multi-targeted TKI, inhibits the activity of BCR-ABL with very high potency and broad specificity, including the T315I mutation which confers resistance to other TKIs. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 58-65 24552773-3 2014 The purpose of this investigation was aimed at exploring whether ponatinib (AP24534), a novel effective TKI against T315I Bcr-Abl, was active against D816V KIT. ponatinib 76-83 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 122-129 24552773-3 2014 The purpose of this investigation was aimed at exploring whether ponatinib (AP24534), a novel effective TKI against T315I Bcr-Abl, was active against D816V KIT. ponatinib 65-74 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 122-129 24180494-1 2013 BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). ponatinib 12-21 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 90-97 24408322-5 2014 Resistance could be overcome with ponatinib, a multikinase inhibitor that targets BCR-ABL and FGF receptor. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 82-89 24297701-0 2014 BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 0-7 24258348-7 2014 Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harbouring T315I. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 25-28 24258348-7 2014 Thus, a third-generation ABL TKI, ponatinib, was developed to inhibit all mutated BCR-ABL and showed clinical efficacy in CML cells harbouring T315I. ponatinib 34-43 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 82-89 24756787-9 2014 In conclusion, ponatinib has proved to be a powerful BCR-ABL inhibitor, which exhibits clinical activity both in BCR-ABL wild-type and mutant CML, including activity against the T315I mutation. ponatinib 15-24 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 53-60 24756787-9 2014 In conclusion, ponatinib has proved to be a powerful BCR-ABL inhibitor, which exhibits clinical activity both in BCR-ABL wild-type and mutant CML, including activity against the T315I mutation. ponatinib 15-24 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 113-120 23888935-1 2013 WHAT IS KNOWN AND OBJECTIVE: Ponatinib is a potent oral tyrosine kinase inhibitor with activity against BCR-ABL, the primary driver of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. ponatinib 29-38 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 104-111 24236021-0 2013 Ponatinib is a pan-BCR-ABL kinase inhibitor: MD simulations and SIE study. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 19-26 24236021-3 2013 The pan-BCR-ABL kinase inhibitor ponatinib exhibits potent activity against native, T315I, and all other clinically relevant mutants, and showed better inhibition than the previously known inhibitors. ponatinib 33-42 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 8-15 24236021-4 2013 We have studied the molecular dynamics simulations and calculated solvated interaction energies of native and fourteen mutant BCR-ABL kinases (M244V, G250E, Q252H, Y253F, Y253H, E255K, E255V, T315A, T315I, F317L, F317V, M351T, F359V and H396P) complexed with ponatinib. ponatinib 259-268 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 126-133 24236021-5 2013 These studies revealed that the interactions between ponatinib and individual residues in BCR-ABL kinase are also affected due to the remote residue mutations. ponatinib 53-62 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 90-97 24236021-7 2013 Our work provides the molecular mechanisms of native and mutant BCR-ABL kinases inhibition by ponatinib at atomic level that has not been studied before. ponatinib 94-103 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 64-71 24180494-1 2013 BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). ponatinib 12-21 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 109-116 24159169-0 2013 Activity of omacetaxine mepesuccinate against ponatinib-resistant BCR-ABL-positive cells. ponatinib 46-55 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 66-73 23787070-4 2013 Ponatinib (AP24534) an orally active Bcr-Abl Tyrosine Kinase Inhibitor and Bafetinib (INNO-406) have efficacy against various point mutations in the Bcr-Abl kinase. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 37-44 23986642-5 2013 Ponatinib (Iclusig ), an orally available, pan-tyrosine kinase inhibitor has a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 127-134 23986642-5 2013 Ponatinib (Iclusig ), an orally available, pan-tyrosine kinase inhibitor has a unique binding mechanism allowing inhibition of BCR-ABL kinases, including those with the T315I point mutation. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 127-134 23787070-4 2013 Ponatinib (AP24534) an orally active Bcr-Abl Tyrosine Kinase Inhibitor and Bafetinib (INNO-406) have efficacy against various point mutations in the Bcr-Abl kinase. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 149-156 23787070-4 2013 Ponatinib (AP24534) an orally active Bcr-Abl Tyrosine Kinase Inhibitor and Bafetinib (INNO-406) have efficacy against various point mutations in the Bcr-Abl kinase. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 37-44 23787070-4 2013 Ponatinib (AP24534) an orally active Bcr-Abl Tyrosine Kinase Inhibitor and Bafetinib (INNO-406) have efficacy against various point mutations in the Bcr-Abl kinase. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 149-156 23684619-0 2013 Efficacy of ponatinib against ABL tyrosine kinase inhibitor-resistant leukemia cells. ponatinib 12-21 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 30-33 23684619-10 2013 This study demonstrates that ponatinib has an anti-leukemia effect by reducing ABL and Lyn kinase activity and this information may be of therapeutic relevance. ponatinib 29-38 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 79-82 23576564-5 2013 Among TKIs tested, ponatinib showed the most robust capacity for apoptotic commitment showing sustained suppression of BCR-ABL signaling even at low intracellular levels following extensive washout, consistent with high-affinity binding and slow dissociation from ABL kinase. ponatinib 19-28 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 119-126 23576564-5 2013 Among TKIs tested, ponatinib showed the most robust capacity for apoptotic commitment showing sustained suppression of BCR-ABL signaling even at low intracellular levels following extensive washout, consistent with high-affinity binding and slow dissociation from ABL kinase. ponatinib 19-28 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 123-126 23372106-2 2013 Five currently available BCR-ABL inhibitors form the mainstay of CML treatment, including first-generation imatinib and more potent second-generation BCR-ABL inhibitors dasatinib and nilotinib, with bosutinib and ponatinib having been recently approved for market inclusion. ponatinib 213-222 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 25-32 23616953-1 2013 Ponatinib is a novel, next-generation, small-molecule tyrosine kinase inhibitor with potent activity against the BCR-ABL fusion oncogene as well as all other ABL kinase domain mutations that confer resistance to earlier generation tyrosine kinase inhibitors. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 113-120 23238683-4 2012 In this line, ponatinib (AP24534) has emerged as a promising therapeutic option in patients with all kinds of BCR-ABL mutations, especially the T315I one. ponatinib 14-23 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 110-117 22781593-3 2013 Ponatinib (AP24534), which potently inhibits native and mutant BCR-ABL, also targets the FGFR family. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 63-70 22781593-3 2013 Ponatinib (AP24534), which potently inhibits native and mutant BCR-ABL, also targets the FGFR family. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 63-70 23190395-8 2012 Using 1 as a competitive probe, we determined the extent to which ponatinib, a clinical Bcr-Abl inhibitor, targets Src-family kinases. ponatinib 66-75 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 88-95 23223358-2 2013 The third-generation ABL1 TKI ponatinib is effective against BCR-ABL1 point mutants individually, but remains vulnerable to certain BCR-ABL1 compound mutants. ponatinib 30-39 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 21-25 23409026-14 2013 After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. ponatinib 65-74 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 195-202 23409026-14 2013 After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid leukemia along with imatinib, all of which vary in their effectiveness against mutated BCR-ABL forms, detection of pre-existing BCR-ABL mutations can help in selection of appropriate first-line drug therapy. ponatinib 65-74 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 236-243 23238683-7 2012 Our results show that ponatinib is highly effective on both sensitive and resistant CML cell lines, whatever the mode of resistance and also on BaF3 murine B cells carrying native BCR-ABL or T315I mutation. ponatinib 22-31 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 180-187 23190221-2 2012 Ponatinib (AP24534) is a potent oral tyrosine kinase inhibitor that blocks native and mutated BCR-ABL, including the gatekeeper mutant T315I, which is uniformly resistant to tyrosine kinase inhibitors. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 94-101 23190221-2 2012 Ponatinib (AP24534) is a potent oral tyrosine kinase inhibitor that blocks native and mutated BCR-ABL, including the gatekeeper mutant T315I, which is uniformly resistant to tyrosine kinase inhibitors. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 94-101 23190221-14 2012 CONCLUSIONS: Ponatinib was highly active in heavily pretreated patients with Ph-positive leukemias with resistance to tyrosine kinase inhibitors, including patients with the BCR-ABL T315I mutation, other mutations, or no mutations. ponatinib 13-22 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 174-181 23044928-5 2012 Furthermore, the activity profile of ponatinib and DCC-2036 against a panel of 24 clinically relevant BCR/ABL mutants is presented and compared to the other TKIs. ponatinib 37-46 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 102-109 21098337-5 2011 The leading third-generation clinical candidate for treatment-refractory CML, including patients with the T315I mutation, is ponatinib (AP24534), a pan-BCR-ABL inhibitor that has entered pivotal phase 2 testing. ponatinib 125-134 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 152-159 22778153-0 2012 The novel BCR-ABL and FLT3 inhibitor ponatinib is a potent inhibitor of the MDR-associated ATP-binding cassette transporter ABCG2. ponatinib 37-46 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 10-17 22778153-1 2012 Ponatinib is a novel tyrosine kinase inhibitor with potent activity against BCR-ABL with mutations, including T315I, and also against fms-like tyrosine kinase 3. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 76-83 22778153-6 2012 The ponatinib IC(50) values of BCR-ABL-expressing K562 cells transfected with ABCB1 and ABCG2 were approximately the same as and 2-fold higher than that of K562, respectively, consistent with ponatinib being a substrate of both proteins, but inhibiting its own transport, and resistance was also attenuated to a small degree by ponatinib-induced downregulation of ABCB1 and ABCG2 cell-surface expression on resistant K562 cells. ponatinib 4-13 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-38 21482694-1 2011 Ponatinib (AP24534) is a novel multitargeted kinase inhibitor that potently inhibits native and mutant BCR-ABL at clinically achievable drug levels. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 103-110 21482694-1 2011 Ponatinib (AP24534) is a novel multitargeted kinase inhibitor that potently inhibits native and mutant BCR-ABL at clinically achievable drug levels. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 103-110 23187745-7 2012 The third-generation TKI ponatinib is a BCR-ABL inhibitor that has demonstrated significant activity, including in patients with the TKI resistance mutation T315I. ponatinib 25-34 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 40-47 22532521-0 2012 Platelet dysfunction associated with ponatinib, a new pan BCR-ABL inhibitor with efficacy for chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitor therapy. ponatinib 37-46 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 58-65 22778153-6 2012 The ponatinib IC(50) values of BCR-ABL-expressing K562 cells transfected with ABCB1 and ABCG2 were approximately the same as and 2-fold higher than that of K562, respectively, consistent with ponatinib being a substrate of both proteins, but inhibiting its own transport, and resistance was also attenuated to a small degree by ponatinib-induced downregulation of ABCB1 and ABCG2 cell-surface expression on resistant K562 cells. ponatinib 192-201 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-38 22778153-6 2012 The ponatinib IC(50) values of BCR-ABL-expressing K562 cells transfected with ABCB1 and ABCG2 were approximately the same as and 2-fold higher than that of K562, respectively, consistent with ponatinib being a substrate of both proteins, but inhibiting its own transport, and resistance was also attenuated to a small degree by ponatinib-induced downregulation of ABCB1 and ABCG2 cell-surface expression on resistant K562 cells. ponatinib 192-201 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 31-38 22519766-6 2012 Ponatinib, a pan BCR-ABL TKI, while still under investigation, is very hopeful with its ability to overcome T315I mutations in resistant CML and Ph + ALL patients. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 17-24 22503441-3 2012 Here we review structure-based approaches underlying the development of several molecules that are currently in clinical trials, including the cMet inhibitor ARQ197 and the Bcr-Abl inhibitor ponatinib. ponatinib 191-200 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 173-180 22238366-2 2012 Ponatinib (AP24534) is an oral multitargeted tyrosine kinase inhibitor being explored in a pivotal phase II trial in patients with chronic myelogenous leukemia due to its potent activity against BCR-ABL. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 195-202 22238366-2 2012 Ponatinib (AP24534) is an oral multitargeted tyrosine kinase inhibitor being explored in a pivotal phase II trial in patients with chronic myelogenous leukemia due to its potent activity against BCR-ABL. ponatinib 11-18 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 195-202 22956142-5 2012 Using Imatinib and BCR/ABL as a paradigm for a drug-target pair, we reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations, which has helped in designing the next-generation BCR/ABL inhibitors such as Nilotinib, Dasatinib, and Ponatinib. ponatinib 286-295 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 19-26 22956142-5 2012 Using Imatinib and BCR/ABL as a paradigm for a drug-target pair, we reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations, which has helped in designing the next-generation BCR/ABL inhibitors such as Nilotinib, Dasatinib, and Ponatinib. ponatinib 286-295 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 233-240 21700550-6 2011 The first evaluations of AP24534 present this drug as a potent multi-targeted kinase inhibitor active against T315I and all other BCR-ABL mutants. ponatinib 25-32 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 130-137 35551463-2 2022 The approval of BCR::ABL1 tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib and ponatinib marked a milestone in targeted therapy only for a subset of patients carrying the translocation t(9;22)(q34;q11). ponatinib 102-111 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 21-25 19878872-3 2009 We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. ponatinib 47-54 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 145-152 19878872-5 2009 Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML. ponatinib 41-48 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 58-65 34959482-5 2021 The first, second, and third generation inhibitors (imatinib, dasatinib, nilotinib, bosutinib, and ponatinib) of BCR-ABL1 and the allosteric inhibitor asciminib showed deep genetic and molecular remission rates in CML, leading to the evaluation of treatment discontinuation in prospective trials. ponatinib 99-108 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 117-121 34699069-1 2022 The BCR-ABL1 inhibitor ponatinib is approved for the treatment of adults with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I mutation. ponatinib 23-32 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 8-12 34659899-0 2021 Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressing BCR-ABL1 T315I-compound mutations. ponatinib 14-23 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 94-98 34659899-1 2021 Ponatinib is a tyrosine kinase inhibitor (TKI) directed against BCR-ABL1 which is successfully used in patients with BCR-ABL1 T315I+ chronic myeloid leukemia (CML). ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 68-72 34659899-1 2021 Ponatinib is a tyrosine kinase inhibitor (TKI) directed against BCR-ABL1 which is successfully used in patients with BCR-ABL1 T315I+ chronic myeloid leukemia (CML). ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 121-125 34659899-8 2021 Most importantly, we were able to show that the combinations "asciminib+ponatinib" and "asciminib+ponatinib+HU" produce synergistic apoptosis-inducing effects in CD34+/CD38- CML stem cells obtained from patients with chronic phase CML or BCR-ABL1 T315I+ CML blast phase. ponatinib 72-81 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 242-246 34659899-9 2021 Together, asciminib, ponatinib and HU synergize in producing anti-leukemic effects in multi-resistant CML cells, including cells harboring T315I+ BCR-ABL1 compound mutations and CML stem cells. ponatinib 21-30 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 150-154 33774681-0 2021 The role of ponatinib in adult BCR-ABL1 positive acute lymphoblastic leukemia after allogeneic transplantation: a real-life retrospective multicenter study. ponatinib 12-21 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 35-39 34614211-8 2022 The estimated 5-year survival rate for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) exceeds 70% with intensive chemotherapy and ponatinib, a third-generation BCR-ABL1 TKI, and more recent nonchemotherapy regimens using dasatinib or ponatinib with blinatumomab are producing outstanding results. ponatinib 165-174 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 199-203 34276365-7 2021 Moreover, employing immortalized cell lines and primary CD34-positive progenitors, we demonstrate that these modifications lead to reduced BCR-ABL1 sensitivity to imatinib, dasatinib and ponatinib but not nilotinib. ponatinib 187-196 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 143-147 34117218-5 2021 Apoptosis of IM-resistant Ph+ALL cells with T315I mutation of BCR-ABL was also upregulated by LEN in the presence of the newly developed TKI ponatinib. ponatinib 141-150 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 62-69 35412404-2 2022 AREAS COVERED: In this review, the authors discuss the role of ponatinib, an oral pan-inhibitor of BCR-ABL1, with potent activity in heavily pretreated patients, including T315I mutation. ponatinib 63-72 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 103-107 35544670-6 2022 EXPERT OPINION: Ponatinib is a potent pan-BCR-ABL1 TKI with substantial activity in patients with more resistant or advanced CML. ponatinib 16-25 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 46-50 33748144-3 2021 Although the use of the BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib have increased the overall survival of CML patients, their use is limited by drug resistance and severe adverse effects. ponatinib 122-131 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 24-31 35172577-2 2022 Here, we report the design of unique hybrid molecules by combining the two pharmacophores of clinically approved BCR-ABL inhibitor (ponatinib) and HDAC inhibitor (vorinostat) and results of in vitro studies in drug-resistant CML cells. ponatinib 132-141 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 117-120 33907977-4 2021 Ponatinib is a third generation TKI that demonstrates higher binding affinity for ABL1 than first/second generation TKIs. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 82-86 35057108-2 2022 Targeted therapies based on tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib, have revolutionized the treatment of BCR-ABL1-driven leukemia, particularly chronic myeloid leukemia (CML). ponatinib 118-127 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 170-174 33796468-2 2021 Ponatinib is a 3rd generation TKI that binds BCR-ABL1 with high affinity and inhibits most BCR-ABL1 mutants, including the T315I mutation. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 49-53 33796468-2 2021 Ponatinib is a 3rd generation TKI that binds BCR-ABL1 with high affinity and inhibits most BCR-ABL1 mutants, including the T315I mutation. ponatinib 0-9 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 95-99 33107354-5 2021 In this study, we sought to determine ponatinib"s potential utility, a clinically approved and potent cAbl inhibitor, in MPM treatment. ponatinib 38-47 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 102-106 33107354-12 2021 Western blot analysis showed that the activation of Abl signaling was blocked in the ponatinib-treated MMP lines. ponatinib 85-94 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 52-55 33107354-16 2021 CONCLUSION: Ponatinib may offer a new therapeutic strategy for MPM patients based on cAbl signaling pathway inhibition. ponatinib 12-21 ABL proto-oncogene 1, non-receptor tyrosine kinase Homo sapiens 85-89