PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 26186558-9 2015 The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. Adenosine Triphosphate 4-7 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 20-23 29765150-2 2018 AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours. Adenosine Triphosphate 20-23 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 36-39 29384063-7 2018 X-ray crystallographic studies reveal that unlike other kinases, Pim kinases have a hinge region, which forms a unique binding pocket for ATP, offering a target for a large number of potent small-molecule Pim kinase inhibitors. Adenosine Triphosphate 138-141 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 65-68 29384063-7 2018 X-ray crystallographic studies reveal that unlike other kinases, Pim kinases have a hinge region, which forms a unique binding pocket for ATP, offering a target for a large number of potent small-molecule Pim kinase inhibitors. Adenosine Triphosphate 138-141 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 205-208 29042609-0 2017 Structural analysis of PIM1 kinase complexes with ATP-competitive inhibitors. Adenosine Triphosphate 50-53 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 23-27 29042609-2 2017 Several studies demonstrated that inhibition of PIM1 activity is an attractive strategy in fighting overexpressing cancers, while distinct structural features of ATP binding pocket make PIM1 an inviting target for the design of selective inhibitors. Adenosine Triphosphate 162-165 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 186-190 29042609-3 2017 To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Adenosine Triphosphate 107-110 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 38-42 29042609-3 2017 To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Adenosine Triphosphate 107-110 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 163-167 29042609-3 2017 To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Adenosine Triphosphate 141-144 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 38-42 29042609-3 2017 To facilitate development of specific PIM1 inhibitors, in this study we report three crystal structures of ATP-competitive inhibitors at the ATP binding pocket of PIM1. Adenosine Triphosphate 141-144 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 163-167 26824666-6 2016 The apparent Km values for adenosine triphosphate (ATP) were determined to be 45 +- 7, 6.4 +- 2, and 29 +- 5 muM for Pim-1, Pim-2, and Pim-3, respectively. Adenosine Triphosphate 27-49 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 117-122 26824666-6 2016 The apparent Km values for adenosine triphosphate (ATP) were determined to be 45 +- 7, 6.4 +- 2, and 29 +- 5 muM for Pim-1, Pim-2, and Pim-3, respectively. Adenosine Triphosphate 51-54 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 117-122 26824666-9 2016 We have also used an IMAP FP assay to examine whether compound 1, an ATP mimetic inhibitor designed through structure-based drug design, is indeed an ATP-competitive inhibitor of Pim kinases. Adenosine Triphosphate 150-153 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 179-182 26824666-10 2016 Kinetic analysis based on Lineweaver-Burk plots showed that the inhibition mechanism of compound 1 is ATP competitive against all three Pim isoforms. Adenosine Triphosphate 102-105 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 136-139 26459208-2 2015 Pim-2, among the three Pim isoforms, plays a critical role in multiple myeloma yet inhibition of Pim-2 is challenging due to its high affinity for ATP. Adenosine Triphosphate 147-150 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 0-3 26459208-3 2015 A co-crystal structure of a screening hit 1 bound to Pim-1 kinase revealed the key binding interactions of its indazole core within the ATP binding site. Adenosine Triphosphate 136-139 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 53-58 29057057-2 2017 Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3beta through consideration of differences in the ATP binding pockets. Adenosine Triphosphate 179-182 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 83-87 27285051-4 2016 However, cell active pan-Pim inhibitors have proven difficult to develop because Pim-2 has a low Km for ATP and therefore requires a very potent inhibitor to effectively block the kinase activity at cellular ATP concentrations. Adenosine Triphosphate 104-107 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 25-28 27285051-4 2016 However, cell active pan-Pim inhibitors have proven difficult to develop because Pim-2 has a low Km for ATP and therefore requires a very potent inhibitor to effectively block the kinase activity at cellular ATP concentrations. Adenosine Triphosphate 208-211 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 25-28 24975213-3 2014 Therefore, we investigated the effects of a novel ATP-competitive pan-PIM inhibitor, AZD1897, on AML cell growth and survival. Adenosine Triphosphate 50-53 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 70-73 26058458-5 2015 We observed synergistic binding of MgATP and kinase to the sensor, which was used to develop a superior method to evaluate Pim kinase inhibitors featuring label-free determination of inhibition constants. Adenosine Triphosphate 35-40 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 123-126 25582332-3 2015 Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. Adenosine Triphosphate 81-84 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 58-61 25582332-3 2015 Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. Adenosine Triphosphate 102-105 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 58-61 25582332-3 2015 Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. Adenosine Triphosphate 102-105 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 58-61 25582332-3 2015 Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. Adenosine Triphosphate 102-105 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 58-61 24531473-8 2014 Determination of the SKF86002-Pim1 and SKF86002-HCK co-crystal structures confirmed that SKF86002 interacts with the ATP-binding sites of Pim1 and HCK. Adenosine Triphosphate 117-120 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 30-34 25087047-3 2014 A preferential binding mode was suggested by molecular modeling experiments for nitro series and Pim-1/Pim-3 ATP-binding sites. Adenosine Triphosphate 109-112 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 97-102 24474669-4 2014 EXPERIMENTAL DESIGN: Pan-PIM inhibitors have proven difficult to develop because PIM2 has a low Km for ATP and, thus, requires a very potent inhibitor to effectively block the kinase activity at the ATP levels in cells. Adenosine Triphosphate 103-106 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 25-28 24474669-4 2014 EXPERIMENTAL DESIGN: Pan-PIM inhibitors have proven difficult to develop because PIM2 has a low Km for ATP and, thus, requires a very potent inhibitor to effectively block the kinase activity at the ATP levels in cells. Adenosine Triphosphate 199-202 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 25-28 24531473-8 2014 Determination of the SKF86002-Pim1 and SKF86002-HCK co-crystal structures confirmed that SKF86002 interacts with the ATP-binding sites of Pim1 and HCK. Adenosine Triphosphate 117-120 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 138-142 23755147-10 2013 All mutants bound ATP and ATP mimetic inhibitors with comparable IC50 values suggesting that the studied Pim-1 kinase mutants can be efficiently targeted with inhibitors developed for the wild type protein. Adenosine Triphosphate 18-21 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 105-110 25050081-3 2014 Due to their ability to inhibit protein kinases (nanomolar IC50 values against Pim1 at 10 muM ATP), this class of rhenium complexes point into the direction of dual function antiproliferative therapy with a single drug in which photodynamic therapy is combined with the inhibition of cancer related protein kinases. Adenosine Triphosphate 94-97 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 79-83 23755147-10 2013 All mutants bound ATP and ATP mimetic inhibitors with comparable IC50 values suggesting that the studied Pim-1 kinase mutants can be efficiently targeted with inhibitors developed for the wild type protein. Adenosine Triphosphate 26-29 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 105-110 22385334-5 2012 We present ATP-competitive PIM1 inhibitors and the state of the art of PIM1 inhibitor design. Adenosine Triphosphate 11-14 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 27-31 22733119-6 2012 A cocrystal structure of one metallo-phthalimide with the protein kinase Pim1 confirmed an ATP-competitive binding with the intended hydrogen bonding between the phthalimide moiety and the hinge region of the ATP-binding site. Adenosine Triphosphate 91-94 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 73-77 22733119-6 2012 A cocrystal structure of one metallo-phthalimide with the protein kinase Pim1 confirmed an ATP-competitive binding with the intended hydrogen bonding between the phthalimide moiety and the hinge region of the ATP-binding site. Adenosine Triphosphate 209-212 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 73-77 23623490-2 2013 Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. Adenosine Triphosphate 149-152 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 16-19 23616352-1 2013 Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub-nanomolar affinity. Adenosine Triphosphate 47-50 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 79-82 23436791-0 2013 A combination strategy to inhibit Pim-1: synergism between noncompetitive and ATP-competitive inhibitors. Adenosine Triphosphate 78-81 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 34-39 23436791-2 2013 In an effort to discover new potent Pim-1 inhibitors, a previously identified ATP-competitive indolyl-pyrrolone scaffold was expanded to derive structure-activity relationship data. Adenosine Triphosphate 78-81 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 36-41 23436791-6 2013 A synergistic effect in the inhibition of cell proliferation by ATP-competitive and ATP-noncompetitive compounds was also observed in prostate cancer cell lines (PC3), where all Pim-1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel. Adenosine Triphosphate 64-67 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 178-183 23436791-6 2013 A synergistic effect in the inhibition of cell proliferation by ATP-competitive and ATP-noncompetitive compounds was also observed in prostate cancer cell lines (PC3), where all Pim-1 inhibitors tested in showed synergism with the known anticancer agent, paclitaxel. Adenosine Triphosphate 84-87 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 178-183 23004574-8 2012 EXPERT OPINION: To obtain a potent and selective Pim1 inhibitor as a lead compound, the authors propose the development of compounds which simultaneously interact with both the ATP binding site (Lys67, Glu121 and Phe49) and substrate binding residues (Asp128, Asp131 and Glu171). Adenosine Triphosphate 177-180 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 49-53 22306408-3 2012 X-ray crystal analysis of the complex structure of Pim-1 with the inhibitor indicated that the inhibitor actually binds to the ATP-binding site and also forms direct interactions with residues (Asp128 and Glu171) that bind the substrate peptide. Adenosine Triphosphate 127-130 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 51-56 20808948-3 2010 Systematic pair-wise comparison of the staurosporine-binding site of the proto-oncogene Pim-1 kinase with 6,412 druggable protein-ligand binding sites suggested that the ATP-binding site of synapsin I may recognize the pan-kinase inhibitor staurosporine. Adenosine Triphosphate 170-173 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 88-93 22272708-5 2012 Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Adenosine Triphosphate 137-140 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 210-213 34770845-8 2021 They were as effective as small chemical drug inhibitor (AZD1208, which is an ATP competitive inhibitor of all PIM isoforms for ex vivo use) in inhibiting PIM kinase activity. Adenosine Triphosphate 78-81 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 111-114 19723579-2 2009 Here the functional roles of the ATP-dependent protease Pim1/LON and the ClpB-type chaperone Hsp78, both members of the ubiquitous AAA+ (ATPases associated with a wide variety of cellular activities) protein family, are described and discussed in the context of protein homeostasis processes under normal and stress conditions. Adenosine Triphosphate 33-36 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 56-60 16227208-7 2005 We have solved the crystal structure of Pim-1 bound to a high affinity peptide substrate in complexes with either the ATP analog AMP-PNP or the bisindolylmaleimide kinase inhibitor 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide HCl. Adenosine Triphosphate 118-121 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 40-45 15808862-5 2005 Pim1 is unique among protein kinases due to the presence of a proline residue at position 123 that precludes the formation of the canonical second hydrogen bond between the hinge backbone and the adenine moiety of ATP. Adenosine Triphosphate 214-217 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 0-4 9405361-1 1997 The biogenesis of the ATP-dependent PIM1 protease of mitochondria was studied by mutational analysis. Adenosine Triphosphate 22-25 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 36-40 9405361-4 1997 This latter process depended on the ATP-dependent assembly of PIM1 protease subunits and can occur by an intermolecular and, most probably, also an intramolecular pathway. Adenosine Triphosphate 36-39 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 62-66 19788246-7 2009 The structure revealed a non-ATP mimetic binding mode with no hydrogen bonds formed with the kinase hinge region and explained the selectivity of pyrrolo[2,3-a]carbazole derivatives for Pim kinases. Adenosine Triphosphate 29-32 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 186-189 15525646-7 2005 2) The hinge region has a novel architecture and hydrogen-bonding pattern, which not only expand the ATP pocket but also serve to establish unambiguously the alignment of the Pim-1 hinge region with that of other kinases. Adenosine Triphosphate 101-104 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 175-180 7957078-1 1994 ATP dependent proteolytic degradation of misfolded proteins in the mitochondrial matrix is mediated by the PIM1 protease and depends on the molecular chaperone proteins mt-hsp70 and Mdj1p. Adenosine Triphosphate 0-3 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 107-111 34770845-8 2021 They were as effective as small chemical drug inhibitor (AZD1208, which is an ATP competitive inhibitor of all PIM isoforms for ex vivo use) in inhibiting PIM kinase activity. Adenosine Triphosphate 78-81 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 155-158 32473133-6 2020 To understand the molecular interaction between resveratrol and PIM-1, we conducted docking simulation and found that resveratrol directly binds to the PIM-1 at the ATP-binding pocket. Adenosine Triphosphate 165-168 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 64-69 34448628-9 2021 Our findings suggest that identified phytoconstituents Dehydrotectol and Nordracorubin bind to PIM1 in ATP-competitive binding mode. Adenosine Triphosphate 103-106 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 95-99 34012401-5 2021 In silico analysis of binding mode of YPC-21440 and Pim kinases revealed that it directly bound to ATP-binding pockets of Pim kinases. Adenosine Triphosphate 99-102 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 52-55 34012401-5 2021 In silico analysis of binding mode of YPC-21440 and Pim kinases revealed that it directly bound to ATP-binding pockets of Pim kinases. Adenosine Triphosphate 99-102 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 122-125 33448694-3 2020 The three-dimensional crystal structure complex of human Pim-1 with ligand bound revealed an ATP-competitive binding mode. Adenosine Triphosphate 93-96 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 57-62 32473133-6 2020 To understand the molecular interaction between resveratrol and PIM-1, we conducted docking simulation and found that resveratrol directly binds to the PIM-1 at the ATP-binding pocket. Adenosine Triphosphate 165-168 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 152-157 32479955-6 2020 Structural studies of PIM kinases revealed that they have unique hinge regions where two Proline resides and makes ATP binding unique, by offering a target for an increasing number of potent PIM kinase inhibitors. Adenosine Triphosphate 115-118 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 22-25 32479955-6 2020 Structural studies of PIM kinases revealed that they have unique hinge regions where two Proline resides and makes ATP binding unique, by offering a target for an increasing number of potent PIM kinase inhibitors. Adenosine Triphosphate 115-118 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 191-194 31072293-11 2019 Docking analysis showed that AZD1208 is capable of performing hydrophobic interactions with PIM-1 ATP- binding-site residues with stronger interaction-based negative free energy (FEB, kcal/mol) than the ATP itself, mimicking an ATP-competitive inhibitory pattern of interaction. Adenosine Triphosphate 98-101 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 92-97 31072293-12 2019 On the same way, VCR and DNR may theoretically interact at the same biophysical environment of AZD1208 and also compete with ATP by the PIM-1 active site. Adenosine Triphosphate 125-128 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 136-141 31072293-13 2019 These evidences suggest that AZD1208 may induce pharmacodynamic interaction with VCR and DNR, weakening its cytotoxic potential in the ATP-binding site from PIM-1 observed in the in vitro experiments. Adenosine Triphosphate 135-138 Pim-1 proto-oncogene, serine/threonine kinase Homo sapiens 157-162