PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34372559-8 2021 The role of Chk1, a protein kinase known to be involved in the replication stress-induced DDR, was examined by inhibition with the small molecule LY2603618 and by siRNA-mediated knockdown. LY2603618 146-155 checkpoint kinase 1 Homo sapiens 12-16 34169240-5 2021 Synergistic combination of NORA234 and CHK1 (rabusertib) targeting is synthetic lethal inducing death of both CD44v6-negative and CD44v6-positive CRC stem cell fractions, aside from Wnt pathway activity. LY2603618 45-55 checkpoint kinase 1 Homo sapiens 39-43 29286153-3 2018 In the present study, we explored the antitumor mechanism of LY2603618, a specific CHK1 inhibitor, alone or in combination with gemcitabine in 5 pancreatic cancer cell lines. LY2603618 61-70 checkpoint kinase 1 Homo sapiens 83-87 35000525-4 2022 Then, pancreatic Capan-1 cells were repeatedly treated with the PARP1 inhibitor olaparib, the Chk1 inhibitor rabusertib or their combination for 211-214 days, during which the changes in drug sensitivity were monitored at a 35-day interval. LY2603618 109-119 checkpoint kinase 1 Homo sapiens 94-98 35000525-11 2022 Our findings indicate that repeated treatments with the rabusertib/olaparib combination result in increased drug resistance and a more aggressive cell phenotype than those with either single agent, providing new clues for future clinical anticancer tests of PARP1 and Chk1 inhibitor combinations. LY2603618 56-66 checkpoint kinase 1 Homo sapiens 268-272 31209198-6 2019 LY2603618 (Rabusertib), which specifically targets Chk1 kinase, kills HNSCC cells effectively and specifically. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 51-55 31209198-6 2019 LY2603618 (Rabusertib), which specifically targets Chk1 kinase, kills HNSCC cells effectively and specifically. LY2603618 11-21 checkpoint kinase 1 Homo sapiens 51-55 30837643-5 2019 Moreover, CHK1 knockdown or addition of a CHK1 inhibitor such as MK-8776, rabusertib or prexasertib enhances CPX-351-induced apoptosis in multiple TP53-null and TP53-wildtype AML cell lines. LY2603618 74-84 checkpoint kinase 1 Homo sapiens 42-46 28766886-9 2017 Chk-1 inhibitors such as rabusertib increased the cytotoxicity of etoposide/carboplatin to the SCLC lines in an additive to greater than additive manner. LY2603618 25-35 checkpoint kinase 1 Homo sapiens 0-5 28625637-1 2017 This phase 2 portion of a phase 1/2 study examined the efficacy and safety of LY2603618, a selective checkpoint kinase 1 inhibitor, combined with pemetrexed and cisplatin (LY+Pem+Cis) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). LY2603618 78-87 checkpoint kinase 1 Homo sapiens 101-120 28625637-0 2017 A randomized, phase 2 evaluation of the CHK1 inhibitor, LY2603618, administered in combination with pemetrexed and cisplatin in patients with advanced nonsquamous non-small cell lung cancer. LY2603618 56-65 checkpoint kinase 1 Homo sapiens 40-44 27829224-10 2016 We identified two distinct classes of Chk1 inhibitors: those that induced a strong increase in gammaH2AX, pChk1 (S317) and pRPA32 (S4/S8) (including V158411, LY2603618 and ARRY-1A) and those that did not (including MK-8776 and GNE-900). LY2603618 158-167 checkpoint kinase 1 Homo sapiens 38-42 28030798-4 2017 Strikingly, the Chk1-inhibitors AZD7762 and LY2603618 were among the top candidate hits of 1664 tested compounds, suggesting that the synergistic cytotoxic effects are due to increased S-phase DNA damage. LY2603618 44-53 checkpoint kinase 1 Homo sapiens 16-20 27166183-4 2016 In this study, we utilized a CHK1 inhibitor, LY2603618, to decrease Mcl-1 and enhance ABT-199 efficacy. LY2603618 45-54 checkpoint kinase 1 Homo sapiens 29-33 27286453-7 2016 Combination of LY2603618, a specific Chk1/2 inhibitor, with irinotecan resulted in a significant reduction of CRC-SC growth in vivo, confirming that irinotecan treatment coupled to inhibition of Chk1 represents a potentially effective therapeutic approach for CRC treatment. LY2603618 15-24 checkpoint kinase 1 Homo sapiens 37-43 27286453-7 2016 Combination of LY2603618, a specific Chk1/2 inhibitor, with irinotecan resulted in a significant reduction of CRC-SC growth in vivo, confirming that irinotecan treatment coupled to inhibition of Chk1 represents a potentially effective therapeutic approach for CRC treatment. LY2603618 15-24 checkpoint kinase 1 Homo sapiens 37-41 27350064-0 2016 Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer. LY2603618 23-32 checkpoint kinase 1 Homo sapiens 53-57 27350064-1 2016 Introduction LY2603618 is a selective inhibitor of checkpoint kinase 1 (CHK1) protein kinase, a key regulator of the DNA damage checkpoint, and is predicted to enhance the effects of antimetabolites, such as pemetrexed. LY2603618 13-22 checkpoint kinase 1 Homo sapiens 51-70 27350064-1 2016 Introduction LY2603618 is a selective inhibitor of checkpoint kinase 1 (CHK1) protein kinase, a key regulator of the DNA damage checkpoint, and is predicted to enhance the effects of antimetabolites, such as pemetrexed. LY2603618 13-22 checkpoint kinase 1 Homo sapiens 72-76 26288133-0 2015 Phase I study of LY2603618, a CHK1 inhibitor, in combination with gemcitabine in Japanese patients with solid tumors. LY2603618 17-26 checkpoint kinase 1 Homo sapiens 30-34 26612134-0 2016 LY2603618, a selective CHK1 inhibitor, enhances the anti-tumor effect of gemcitabine in xenograft tumor models. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 23-27 26612134-2 2016 We report the preclinical therapeutic activity of LY2603618 (CHK1 inhibitor) at inhibiting CHK1 activation by gemcitabine and enhancing in vivo efficacy. LY2603618 50-59 checkpoint kinase 1 Homo sapiens 61-65 26612134-2 2016 We report the preclinical therapeutic activity of LY2603618 (CHK1 inhibitor) at inhibiting CHK1 activation by gemcitabine and enhancing in vivo efficacy. LY2603618 50-59 checkpoint kinase 1 Homo sapiens 91-95 26612134-6 2016 Co-administration of LY2603618 with gemcitabine showed a clear inhibition of CHK1 autophosphorylation for at least 24 h. Combining LY2603618 with gemcitabine resulted in an increase in H2AX serine 139 phosphorylation, indicating a corresponding increase in damaged DNA in the tumors. LY2603618 21-30 checkpoint kinase 1 Homo sapiens 77-81 26612134-6 2016 Co-administration of LY2603618 with gemcitabine showed a clear inhibition of CHK1 autophosphorylation for at least 24 h. Combining LY2603618 with gemcitabine resulted in an increase in H2AX serine 139 phosphorylation, indicating a corresponding increase in damaged DNA in the tumors. LY2603618 131-140 checkpoint kinase 1 Homo sapiens 77-81 27598338-0 2016 Phase I Study of CHK1 Inhibitor LY2603618 in Combination with Gemcitabine in Patients with Solid Tumors. LY2603618 32-41 checkpoint kinase 1 Homo sapiens 17-21 27598338-1 2016 OBJECTIVE: LY2603618, a selective inhibitor of checkpoint kinase 1 (CHK1) and key regulator of the DNA damage checkpoint, may enhance the effects of antimetabolites. LY2603618 11-20 checkpoint kinase 1 Homo sapiens 47-66 27598338-1 2016 OBJECTIVE: LY2603618, a selective inhibitor of checkpoint kinase 1 (CHK1) and key regulator of the DNA damage checkpoint, may enhance the effects of antimetabolites. LY2603618 11-20 checkpoint kinase 1 Homo sapiens 68-72 26288133-1 2015 This phase I trial evaluated LY2603618, a selective inhibitor of the DNA damage checkpoint kinase 1, in combination with gemcitabine. LY2603618 29-38 checkpoint kinase 1 Homo sapiens 80-99 24114124-11 2014 Treatment of Calu-6 human mutant TP53 lung cancer cell xenografts with gemcitabine resulted in a stimulation of Chk1 kinase activity that was inhibited by co-administration of LY2603618. LY2603618 176-185 checkpoint kinase 1 Homo sapiens 112-116 25296725-0 2015 Evaluation of the likelihood of a selective CHK1 inhibitor (LY2603618) to inhibit CYP2D6 with desipramine as a probe substrate in cancer patients. LY2603618 60-69 checkpoint kinase 1 Homo sapiens 44-48 25296725-1 2015 LY2603618 is a selective inhibitor of deoxyribonucleic acid damage checkpoint kinase 1 (CHK1) and has been in development for the enhancement of chemotherapeutic agents. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 67-86 25296725-1 2015 LY2603618 is a selective inhibitor of deoxyribonucleic acid damage checkpoint kinase 1 (CHK1) and has been in development for the enhancement of chemotherapeutic agents. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 88-92 24942404-1 2014 LY2603618 is an inhibitor of checkpoint kinase 1 (CHK1), an important regulator of the DNA damage checkpoints. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 50-54 24666335-0 2014 Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous administration in patients with advanced and/or metastatic solid tumors. LY2603618 30-39 checkpoint kinase 1 Homo sapiens 43-48 24666335-1 2014 The disposition and metabolism of a Chk-1 inhibitor (LY2603618) was characterized following a 1-h intravenous administration of a single 250-mg dose of [14C]LY2603618 (50 microCi) to patients with advanced or metastatic solid tumors. LY2603618 53-62 checkpoint kinase 1 Homo sapiens 36-41 24666335-1 2014 The disposition and metabolism of a Chk-1 inhibitor (LY2603618) was characterized following a 1-h intravenous administration of a single 250-mg dose of [14C]LY2603618 (50 microCi) to patients with advanced or metastatic solid tumors. LY2603618 157-166 checkpoint kinase 1 Homo sapiens 36-41 24114124-0 2014 Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. LY2603618 48-57 checkpoint kinase 1 Homo sapiens 82-86 24114124-6 2014 LY2603618 is a potent and selective small molecule inhibitor of Chk1 protein kinase activity in vitro (IC(50) = 7 nM) and the first selective Chk1 inhibitor to enter clinical cancer trials. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 64-68 24114124-6 2014 LY2603618 is a potent and selective small molecule inhibitor of Chk1 protein kinase activity in vitro (IC(50) = 7 nM) and the first selective Chk1 inhibitor to enter clinical cancer trials. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 142-146 24114124-7 2014 Treatment of cells with LY2603618 produced a cellular phenotype similar to that reported for depletion of Chk1 by RNAi. LY2603618 24-33 checkpoint kinase 1 Homo sapiens 106-110 24114124-8 2014 Inhibition of intracellular Chk1 by LY2603618 results in impaired DNA synthesis, elevated H2A.X phosphorylation indicative of DNA damage and premature entry into mitosis. LY2603618 36-45 checkpoint kinase 1 Homo sapiens 28-32 24942404-1 2014 LY2603618 is an inhibitor of checkpoint kinase 1 (CHK1), an important regulator of the DNA damage checkpoints. LY2603618 0-9 checkpoint kinase 1 Homo sapiens 29-48 24928205-3 2014 In this study, we investigated the molecular mechanisms underlying the antitumor activity of LY2603618, a potent and selective small molecule inhibitor of Chk1 protein kinase, in human lung cancer cells. LY2603618 93-102 checkpoint kinase 1 Homo sapiens 155-159 24928205-6 2014 LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage-mediated Chk1 phosphorylation (S345 Chk1). LY2603618 0-9 checkpoint kinase 1 Homo sapiens 20-24 24928205-6 2014 LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage-mediated Chk1 phosphorylation (S345 Chk1). LY2603618 0-9 checkpoint kinase 1 Homo sapiens 51-55 24928205-6 2014 LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage-mediated Chk1 phosphorylation (S345 Chk1). LY2603618 0-9 checkpoint kinase 1 Homo sapiens 51-55 24928205-6 2014 LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage-mediated Chk1 phosphorylation (S345 Chk1). LY2603618 0-9 checkpoint kinase 1 Homo sapiens 51-55 24928205-11 2014 These results suggest the following: (i) the biological consequences of LY2603618 in lung cancer cells is associated with both inhibition of Chk1 phosphorylation on S296 and activation of the DNA damage response network; and (ii) the anticancer property of LY2603618 might be increased by inhibiting autophagy. LY2603618 72-81 checkpoint kinase 1 Homo sapiens 141-145 24114124-12 2014 By all criteria, LY2603618 is a highly effective inhibitor of multiple aspects of Chk1 biology. LY2603618 17-26 checkpoint kinase 1 Homo sapiens 82-86 24098799-10 2013 Synergistic antitumor interactions were also observed when the DNA damaging agents were combined with a CHK1-specific inhibitor, LY2603618. LY2603618 129-138 checkpoint kinase 1 Homo sapiens 104-108 22492020-1 2013 PURPOSE: This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. LY2603618 77-86 checkpoint kinase 1 Homo sapiens 113-132 23917378-2 2013 PARP1 inhibitors [AZD2281 ; ABT888 ; NU1025 ; AG014699] interacted with CHK1 inhibitors [UCN-01 ; AZD7762 ; LY2603618] to kill mammary carcinoma cells. LY2603618 108-117 checkpoint kinase 1 Homo sapiens 72-76