Journal ArticleDOI
Mercapturate pathway metabolites of sotorasib, a covalent inhibitor of KRASG12C, are associated with renal toxicity in the Sprague Dawley rat.
Jonathan Werner,Rhian Davies,Jan Wahlstrom,Upendra P. Dahal,Min Jiang,Jonathan Stauber,Benjamin David,William Siska,Barbara Thomas,Katsu Ishida,W. Griffith Humphreys,J. Russell Lipford,Thomas M. Monticello +12 more
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TLDR
In this paper, an in vivo mechanistic rat study designed to investigate the time course of the renal toxicity and sotorasib metabolites was performed, and the morphologic features progressed from vacuolation and necrosis to regeneration of tubular epithelium.About:
This article is published in Toxicology and Applied Pharmacology.The article was published on 2021-07-15. It has received 8 citations till now. The article focuses on the topics: Kidney & Nephrotoxicity.read more
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Journal ArticleDOI
Spotlight on Sotorasib (AMG 510) for KRASG12C Positive Non-Small Cell Lung Cancer.
Shannon S. Zhang,Misako Nagasaka +1 more
TL;DR: Sotorasib as mentioned in this paper, a novel KRASG12C inhibitor, was given conditional approval by the FDA in May 2019, based on promising results in both preclinical and clinical trials.
Journal ArticleDOI
Nonclinical Safety Profile of Sotorasib, a KRASG12C-Specific Covalent Inhibitor for the Treatment of KRAS p.G12C-Mutated Cancer:
Katsu Ishida,Jonathan Werner,Rhian Davies,Fan Fan,Barbara Thomas,Jan Wahlstrom,James Russell Lipford,Thomas M. Monticello +7 more
TL;DR: Sotorasib as mentioned in this paper is a first-in-class KRASG12C covalent inhibitor in clinical development for the treatment of tumors with the KRAS p.g12C mutation.
Journal ArticleDOI
Absorption, Distribution, Metabolism, and Excretion of [14C]-Sotorasib in Rats and Dogs: Interspecies Differences in Absorption, Protein Conjugation and Metabolism
TL;DR: The mass balance, excretion, and metabolism of [14C]-sotorasib was characterized in rats and dogs after a single dose of 60 or 500 mg/kg, respectively, and rapid absorption and extensive metabolism of sotorasIB was observed in rats, while sotor asib was primarily excreted unchanged in dog feces, likely due to solubility-limited absorption.
Journal ArticleDOI
Approved spectrofluorimetric strategies for assurance of three modern antineoplastic drugs; Tepotinib, Sotorasib and Darolutamide in their dose forms and biological liquids utilizing mercurochrome.
Hesham Salem,Noha Abdal-Karim,Bahaa Omran,Abdel-Rahman Abdel-Gayed,Mazen A. A. Atef,M. Abdelgaleel +5 more
TL;DR: In this paper , a straightforward, fast and delicate spectrofluorimetric strategy has been developed for the estimation of tepotinib (TEPO), sotorasib (SOTO) and darolutamide (DARO) as a new antineoplastic drugs.
Journal ArticleDOI
ABCB1 limits brain exposure of the KRASG12C inhibitor sotorasib, whereas ABCB1, CYP3A, and possibly OATP1a/1b restrict its oral availability.
N. Loos,Irene A. Retmana,Wenlong Li,Margarida L. F. Martins,M C Lebre,Rolf W. Sparidans,Jos H. Beijnen,Alfred H. Schinkel +7 more
TL;DR: Sotorasib (Lumakras™) is the first FDA-approved KRASG12C inhibitor for treatment of patients with non-small cell lung cancer (NSCLC) carrying this mutation as discussed by the authors .
References
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Journal ArticleDOI
Ras oncogenes: split personalities
TL;DR: Despite great strides in understanding of the molecular and cellular mechanisms of action of the Ras proteins, the expanding roster of their downstream effectors and the complexity of the signalling cascades that they regulate indicate that much remains to be learnt.
Journal ArticleDOI
Mechanisms of Cisplatin nephrotoxicity.
TL;DR: Recent advances in understanding of cisplatin nephrotoxicity are summarized and it is discussed how these advances might lead to more effective prevention.
Journal ArticleDOI
The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity
Jude Canon,Karen Rex,Anne Y. Saiki,Christopher Mohr,Keegan Cooke,Dhanashri Bagal,Kevin Gaida,Tyler Holt,Charles G. Knutson,Neelima Koppada,Brian A. Lanman,Jonathan Werner,Aaron S. Rapaport,Tisha San Miguel,Roberto Ortiz,Roberto Ortiz,Tao Osgood,Ji Rong Sun,Xiaochun Zhu,Xiaochun Zhu,John D. McCarter,Laurie P. Volak,Laurie P. Volak,Brett E. Houk,Marwan Fakih,Bert H. O'Neil,Timothy J. Price,Gerald Steven Falchook,Jayesh Desai,James Kuo,Ramaswamy Govindan,David S. Hong,Wenjun Ouyang,H. Henary,Tara Arvedson,Victor J. Cee,J. Russell Lipford +36 more
TL;DR: Treatment of KRASG 12C-mutant cancer cells with the KRAS(G12C) inhibitor AMG 510 leads to durable response in mice, and anti-tumour activity in patients suggests that AMG510 could be effective in patients for whom treatments are currently lacking.
Journal ArticleDOI
KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.
David S. Hong,Marwan Fakih,John H. Strickler,Jayesh Desai,G. Durm,Geoffrey I. Shapiro,Gerald S. Falchook,Timothy J. Price,Adrian G. Sacher,Crystal S. Denlinger,Yung-Jue Bang,Grace K. Dy,John C. Krauss,Yasutoshi Kuboki,James Kuo,Andrew L. Coveler,Keunchil Park,Tae Won Kim,Fabrice Barlesi,Pamela N. Munster,Suresh S. Ramalingam,Timothy F. Burns,Funda Meric-Bernstam,H. Henary,J. Ngang,Gataree Ngarmchamnanrith,J. Kim,Brett E. Houk,Jude Canon,J. Russell Lipford,Gregory Friberg,Piro Lito,Ramaswamy Govindan,Bob T. Li +33 more
TL;DR: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation and responded to pharmacokinetics and objective response according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.