Multivalent Small-Molecule Pan-RAS Inhibitors

Cell

Volumn 168, Issue 5, 2017, Pages 878-889.e29

  Welsch, Matthew E ^a   Kaplan, Anna ^a   Chambers, Jennifer M ^a   Stokes, Michael E ^a   Bos, Pieter H ^a   Zask, Arie ^a   Zhang, Yan ^a   Sanchez Martin, Marta ^b   Badgley, Michael A ^b   Huang, Christine S ^a   Tran, Timothy H ^a   Akkiraju, Hemanth ^a   Brown, Lewis M ^a   Nandakumar, Renu ^b   Cremers, Serge ^b   Yang, Wan Seok ^c   Tong, Liang ^a   Olive, Kenneth P ^b   Ferrando, Adolfo ^b   Stockwell, Brent R ^a  

^a Columbia University ^*  (United States)

^b Department of Medicine   (United States)

^c ST JOHN'S UNIVERSITY   (United States)

Author keywords

cancer; chemical biology; drug design; GTPase; Hras; Kras; multivalent; Nras; Ras; small molecule

Indexed keywords

1 (2,6 DICHLOROBENZYL)PIPERAZINE; 3 [5 [[4 (2,6 DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENYL] 1H INDOL 1 YL]PROPAN 1 AMINE; 4 AMINO N [3 [4 [[4 [2 (4 CHLOROPHENOXY)ETHYL]PIPERAZIN 1 YL]METHYL] 3 (2 METHOXYPHENYL) 1H INDOL 1 YL]PROPYL]PIPERIDINE 4 CARBOXAMIDE; 4 AMINO N [3 [4 [[4 [2 (4 CHLOROPHENOXY)ETHYL]PIPERAZIN 1 YL]METHYL] 3 (3 FLUOROPHENYL) 1H INDOL 1 YL]PROPYL]PIPERIDINE 4 CARBOXAMIDE; 4 AMINO N [3 [5 [[4 (2,6 DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENYL 1H INDOL 1 YL]PROPYL]PIPERIDINE 4 CARBOXAMIDE; 4 [[3 CHLORO 4 [(4 FLUOROBENZYL)OXY]BENZYL]AMINO] N [3 [4 [[4 [2 (4 CHLOROPHENOXY)ETHYL]PIPERAZIN 1 YL]METHYL] 3 (3 FLUOROPHENYL) 1H INDOL 1 YL]PROPYL]PIPERIDINE 4 CARBOXAMIDE; 4 [[4 [[3,5 BIS(TRIFLUOROMETHYL)BENZYL]OXY]BENZYL]AMINO] N [3 [5- [[4 (2,6 DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENYL] 1H INDOL 1 YL]PROPYL]PIPERIDINE 4 CARBOXAMIDE; 4 [[5 CHLORO 2 [[4 (TRIFLUOROMETHOXY)BENZYL]OXY]BENZYL]AMINO] N [3 [4 [[4 [2 (4 CHLOROPHENOXY)ETHYL]PIPERAZIN 1 YL]METHYL] 3 (3 FLUOROPHENYL) 1H INDOL 1 YL]PROPYL]PIPERIDINE 4 CARBOXAMIDE; 5 CHLORO 2 [4 (TRIFLUOROMETHOXY)BENZYLOXY]BENZALDEHYDE; ANTINEOPLASTIC AGENT; B RAF KINASE; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; H RAS PROTEIN; K RAS PROTEIN; N 3 [5 [[4 (2,6-DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENYL] 1H INDOL 1 YL]PROPYL] 4 [[4 [(3,5 DIMETHOXYBENZYL)OXY] 3 METHOXYBENZYL]AMINO]PIPERIDINE 4 CARBOXAMIDE; N RAS PROTEIN; N [3 [5 [[4 (2,6 DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENYL] 1H INDOL 1 YL]PROPYL] 4 [[[5 (2 ISOPROPOXYPHENYL)PYRIDIN 2 YL]METHYL]AMINO]PIPERIDINE 4 CARBOXAMIDE; N [3 [5 [[4 (3,5 BIS(TRIFLUOROMETHYL)BENZYL]PIPERAZIN 1 YL]METHYL] 3 [2,6 BIS(TRIFLUOROMETHYL)PHENYL] 1H INDOL 1 YL]PROPYL]PIPERAZINE 2 CARBOXAMIDE; N [3 [5 [[4 (3,5 DIMETHOXYBENZYL)PIPERAZIN 1 YL]METHYL] 3 (2,4 DIMETHOXYPHENYL) 1H INDOL 1 YL]PROPYL]PIPERAZINE 2 CARBOXAMIDE; PAN RAS INHIBITOR; PROTEIN; RAS PROTEIN; TAMOXIFEN; TERT 3 [5 [[4 (2,6 DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENY] 1H INDOL 1 YL]PROPYLCARBAMATE; TERT BUTYL 3 (3 BROMO 5 FORMYL 1H INDOL 1 YL)PROPYLCARBAMATE; TERT BUTYL 3 (5 FORMYL 1H INDOL 1 YL)PROPYLCARBAMATE; TERT BUTYL 3 [5 FORMYL 3 [4 (TRIFLUOROMETHOXY)PHENYL] 1H INDOL 1 YL]PROPYLCARBAMATE; TERT BUTYL 4 AMINO 4 [3 [5 [[4 (2,6 DICHLOROBENZYL)PIPERAZIN 1 YL]METHYL] 3 [4 (TRIFLUOROMETHOXY)PHENYL] 1H INDOL 1 YL]PROPYLCARBAMOYL]PIPERIDINE 1 CARBOXYLATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VEMURAFENIB; KRAS PROTEIN, HUMAN; MOLECULAR LIBRARY; PROTEIN P21;

ADULT; ANALYTIC METHOD; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BINDING AFFINITY; BINDING SITE; CANCER INHIBITION; CANCER MODEL; CELL DEATH; CONTROLLED STUDY; CRYSTAL STRUCTURE; DISSOCIATION CONSTANT; DRUG STRUCTURE; DRUG SYNTHESIS; EMBRYO; FIBROBLAST; FLUORINE NUCLEAR MAGNETIC RESONANCE; GENE OVEREXPRESSION; HETERONUCLEAR SINGLE QUANTUM COHERENCE; HUMAN; HUMAN CELL; IN VITRO STUDY; ISOTHERMAL TITRATION CALORIMETRY; LIVER MICROSOME; MALE; MASS SPECTROMETRY; MICROSCALE THERMOPHORESIS; MICROSOME; MOUSE; NITROGEN NUCLEAR MAGNETIC RESONANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT; WILD TYPE; ACUTE LYMPHOBLASTIC LEUKEMIA; ANIMAL; ANTAGONISTS AND INHIBITORS; CALORIMETRY; CANCER TRANSPLANTATION; CELL LINE; CHEMISTRY; METABOLISM; MOLECULAR LIBRARY; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PANCREATIC NEOPLASMS; XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CALORIMETRY; CELL LINE; FIBROBLASTS; HETEROGRAFTS; HUMANS; MICE; MOLECULAR TARGETED THERAPY; NEOPLASM TRANSPLANTATION; NEOPLASMS; PANCREATIC NEOPLASMS; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROTO-ONCOGENE PROTEINS P21(RAS); SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES;

EID: 85014099452     PISSN: 00928674     EISSN: 10974172     Source Type: Journal    
DOI: 10.1016/j.cell.2017.02.006     Document Type: Article

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