Abstract 3595: RMC-6291, a next-generation tri-complex KRASG12C(ON) inhibitor, outperforms KRASG12C(OFF) inhibitors in preclinical models of KRASG12C cancers

Name: Work Video:
Duration: 3 min 30 s
Robert J. Nichols; Yu Chi Yang; Jim Cregg; Chris J. Schulze; Zhican Wang; Richa Dua; Jingjing Jiang; Lindsay S. Garrenton; Nicole Nasholm; Alun Bermingham; John E. Knox; Kyle J. Seamon; Michael Longhi; Kang-Jye Chou; Shaoling Li; David Wildes; Mallika Singh; Elena S. Koltun; Adrian L. Gill; Jacqueline A.M. Smith
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'ON': [122], 'form.': [123], 'Direct': [124], 'inhibition': [125], 'first': [130], 'class,': [132], 'potent,': [133], 'orally': [134], 'bioavailable,': [135], 'selective,': [136], 'tri-complex': [137, 171, 187, 414], 'inhibitor': [138, 155, 165, 337], 'RMC-6291,': [139, 411], 'represents': [140], 'more': [142], 'robust': [143], 'approach': [144], 'presents': [146], 'possibility': [148], 'that': [149, 168, 309, 340], 'RMC-6291': [150, 160, 218, 259, 284, 317, 332], 'will': [151], '‘best-in-class’': [154], 'tumors': [157], 'harboring': [158], 'potent': [163], 'covalent': [164], 'forms': [169], 'within': [172], 'tumor': [173, 230, 235, 274], 'between': [175], 'cyclophilin': [178], 'A': [179], '(CypA),': [180], 'highly': [182], 'abundant': [183], 'immunophilin.': [184], 'assembled': [186], 'prevents': [188], 'from': [190], 'steric': [193], 'blockade': [194], 'RAS': [196, 207, 225, 307], 'effector': [197, 208], 'binding.': [198], 'cells,': [200], 'kinetic': [201], 'analyses': [202], 'demonstrate': [203], 'near-immediate': [204], 'disruption': [205], 'binding': [209], 'extinction': [211], 'signaling.': [214], 'Oral': [215], 'administration': [216], 'produces': [219], 'deep': [220], 'durable': [222], 'suppression': [223], 'pathway': [226], 'activity': [227], 'models': [231, 255, 295, 328, 349, 422], 'profound': [234], 'regressions': [236], 'vivo': [238], 'at': [239], 'well-tolerated': [240], 'doses.': [241], 'mouse': [244], 'clinical': [245], 'trial': [246], 'consisting': [247], 'multiple': [249], 'patient-': [250], 'line-derived': [253], 'xenograft': [254], 'NSCLC,': [258], 'outperformed': [260], 'adagrasib,': [261], 'inhibitor,': [264, 416], 'increasing': [266], 'number': [268], 'responses,': [270], 'depth': [272], 'regressions,': [275], 'durability': [278], 'responses.': [280], 'Combination': [281], 'SHP2': [286], 'or': [287], 'SOS1': [288], 'was': [290], 'well': [291, 320], 'tolerated': [292], 'preclinical': [294, 348, 421], 'further': [297], 'anti-tumor': [299, 330], 'activity,': [300], 'likely': [301], 'preventing': [303], 'wild-type': [306], 'proteins': [308], 'cooperate': [310], 'fuel': [314], 'growth.': [316], 'also': [318], 'combined': [319], 'immune': [322], 'checkpoint': [323], 'inhibitors,': [324], 'sensitizing': [325], 'KRASG12C-bearing': [326], 'immunity.': [331], 'next-generation,': [335], 'mutant-selective': [336], 'overcomes': [341], 'limitations': [342], 'first-generation': [344], 'directly': [351], 'targeting': [352], 'form': [355], 'important': [358], 'driver.': [360], 'Citation': [361], 'Format:': [362], 'Robert': [363], 'J.': [364, 371], 'Nichols,': [365], 'Y.C.': [366], 'Yang,': [367], 'Jim': [368], 'Cregg,': [369], 'Chris': [370], 'Schulze,': [372], 'Zhican': [373], 'Wang,': [374], 'Richa': [375], 'Dua,': [376], 'Jingjing': [377], 'Jiang,': [378], 'Lindsay': [379], 'S.': [380, 403], 'Garrenton,': [381], 'Nicole': [382], 'Nasholm,': [383], 'Alun': [384], 'Bermingham,': [385], 'John': [386], 'E.': [387], 'Knox,': [388], 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'2024-12-25T02:37:14.905210', 'created_date': '2022-06-17'}
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