Sotorasib (BioDeep_00001871414)
代谢物信息卡片
化学式: C30H30F2N6O3 (560.2347)
中文名称:
谱图信息:
最多检出来源 () 0%
分子结构信息
SMILES: CC1CN(CCN1C2=NC(=O)N(C3=NC(=C(C=C32)F)C4=C(C=CC=C4F)O)C5=C(C=CN=C5C(C)C)C)C(=O)C=C
InChI: InChI=1S/C30H30F2N6O3/c1-6-23(40)36-12-13-37(18(5)15-36)28-19-14-21(32)26(24-20(31)8-7-9-22(24)39)34-29(19)38(30(41)35-28)27-17(4)10-11-33-25(27)16(2)3/h6-11,14,16,18,39H,1,12-13,15H2,2-5H3/t18-/m0/s1
描述信息
A pyridopyrimidine that is pyrido[2,3-d]pyrimidin-2(1H)-one substituted by 4-methyl-2-(propan-2-yl)pyridin-3-yl, (2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl, fluoro and 2-fluoro-6-hydroxyphenyl groups at positions 1, 4, 6 and 7, respectively. It is approved for the treatment of patients with non-small cell lung cancer having KRAS(G12C) mutations.
D000970 - Antineoplastic Agents > D000074322 - Antineoplastic Agents, Immunological > D000082082 - Immune Checkpoint Inhibitors
C274 - Antineoplastic Agent > C163758 - Targeted Therapy Agent > C1902 - Ras Inhibitor
L - Antineoplastic and immunomodulating agents > L01 - Antineoplastic agents
C274 - Antineoplastic Agent > C2189 - Signal Transduction Inhibitor
Sotorasib (AMG-510) is a first-in-class, orally bioavailable, and selective KRAS G12C covalent inhibitor. Sotorasib irreversibly inhibits KRAS G12C by locking it in an inactive GDP-bound state. Sotorasib is the first KRAS G12C inhibitor in clinical development and leads to the regression of KRAS G12C tumors[1][2].
Sotorasib racemate (Compound A) is an orally active racemate of Sotorasib (HY-114277), a covalent inhibitor of KRAS G12C mutant which induces adaptive feedback activation of MAPK pathway. Sotorasib racemate also exerts inhibitor activity against KRAS G12C induced cancer and can be applied to cancer research[1].
同义名列表
4 个代谢物同义名
Sotorasib; AMG-510; AMG-510 (racemate); Sotorasib (racemate)
数据库引用编号
10 个数据库交叉引用编号
- ChEBI: CHEBI:178199
- PubChem: 137278711
- DrugBank: DB15569
- ChEMBL: CHEMBL4535757
- CAS: 2252403-56-6
- CAS: 2296729-66-1
- CAS: 2296729-00-3
- MetaboLights: MTBLC178199
- medchemexpress: HY-114277
- medchemexpress: HY-114277A
分类词条
相关代谢途径
Reactome(0)
BioCyc(0)
PlantCyc(0)
代谢反应
0 个相关的代谢反应过程信息。
Reactome(0)
BioCyc(0)
WikiPathways(0)
Plant Reactome(0)
INOH(0)
PlantCyc(0)
COVID-19 Disease Map(0)
PathBank(0)
PharmGKB(0)
0 个相关的物种来源信息
在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：
- PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
- NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
- Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
- Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。
点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。
| 亚细胞结构定位 | 关联基因列表 |
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文献列表
- Upendra P Dahal, Brooke M Rock, John Rodgers, Xiaomeng Shen, Zhe Wang, Jan L Wahlstrom. Absorption, Distribution, Metabolism, and Excretion of [14C]-Sotorasib in Rats and Dogs: Interspecies Differences in Absorption, Protein Conjugation and Metabolism.
Drug metabolism and disposition: the biological fate of chemicals.
2022 05; 50(5):600-612. doi:
10.1124/dmd.121.000798. [PMID: 35153196] - Joshua M Bauml, Bob T Li, Vamsidhar Velcheti, Ramaswamy Govindan, Alessandra Curioni-Fontecedro, Christophe Dooms, Toshiaki Takahashi, Andrew W Duda, Justin I Odegaard, Fernando Cruz-Guilloty, Liming Jin, Ying Zhang, Abraham Anderson, Ferdinandos Skoulidis. Clinical validation of Guardant360 CDx as a blood-based companion diagnostic for sotorasib.
Lung cancer (Amsterdam, Netherlands).
2022 04; 166(?):270-278. doi:
10.1016/j.lungcan.2021.10.007. [PMID: 34838325] - Nancy H C Loos, Irene A Retmana, Wenlong Li, Margarida L F Martins, Maria C Lebre, Rolf W Sparidans, Jos H Beijnen, Alfred H Schinkel. ABCB1 limits brain exposure of the KRASG12C inhibitor sotorasib, whereas ABCB1, CYP3A, and possibly OATP1a/1b restrict its oral availability.
Pharmacological research.
2022 04; 178(?):106137. doi:
10.1016/j.phrs.2022.106137. [PMID: 35192958] - Hesham Salem, Noha Abdal-Karim, Bahaa Omran, Abdel-Rahman Abdel-Gayed, Mazen Atef, Mahmoud Abdelgaleel. Approved spectrofluorimetric strategies for assurance of three modern antineoplastic drugs: tepotinib, sotorasib, and darolutamide in their dose forms and biological liquids utilizing mercurochrome.
Luminescence : the journal of biological and chemical luminescence.
2022 Apr; 37(4):656-664. doi:
10.1002/bio.4206. [PMID: 35142060] - Marwan G Fakih, Scott Kopetz, Yasutoshi Kuboki, Tae Won Kim, Pamela N Munster, John C Krauss, Gerald S Falchook, Sae-Won Han, Volker Heinemann, Kei Muro, John H Strickler, David S Hong, Crystal S Denlinger, Gustavo Girotto, Myung-Ah Lee, Haby Henary, Qui Tran, Joseph K Park, Gataree Ngarmchamnanrith, Hans Prenen, Timothy J Price. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial.
The Lancet. Oncology.
2022 01; 23(1):115-124. doi:
10.1016/s1470-2045(21)00605-7. [PMID: 34919824] - Katsu Ishida, Jonathan A Werner, Rhian Davies, Fan Fan, Barbara Thomas, Jan Wahlstrom, James Russell Lipford, Thomas Monticello. Nonclinical Safety Profile of Sotorasib, a KRASG12C-Specific Covalent Inhibitor for the Treatment of KRAS p.G12C-Mutated Cancer.
International journal of toxicology.
2021 10; 40(5):427-441. doi:
10.1177/10915818211022965. [PMID: 34137282] - Hema Adhikari, Walaa E Kattan, Shivesh Kumar, Pei Zhou, John F Hancock, Christopher M Counter. Oncogenic KRAS is dependent upon an EFR3A-PI4KA signaling axis for potent tumorigenic activity.
Nature communications.
2021 09; 12(1):5248. doi:
10.1038/s41467-021-25523-5. [PMID: 34504076] - Jonathan A 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. Mercapturate pathway metabolites of sotorasib, a covalent inhibitor of KRASG12C, are associated with renal toxicity in the Sprague Dawley rat.
Toxicology and applied pharmacology.
2021 07; 423(?):115578. doi:
10.1016/j.taap.2021.115578. [PMID: 34004237] - Irene A Retmana, Nancy H C Loos, Alfred H Schinkel, Jos H Beijnen, Rolf W Sparidans. Quantification of KRAS inhibitor sotorasib in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.
2021 Jun; 1174(?):122718. doi:
10.1016/j.jchromb.2021.122718. [PMID: 33957355] - Naveena Madhyastha, Swapan Kumar Samantha, Sreekanth Dittakavi, Meenu Markose, Sadanand Rangnathrao Mallurwar, Mohd Zainuddin, Ramesh Mullangi. Validated HPLC-MS/MS method for quantitation of AMG 510, a KRAS G12C inhibitor, in mouse plasma and its application to a pharmacokinetic study in mice.
Biomedical chromatography : BMC.
2021 Apr; 35(4):e5043. doi:
10.1002/bmc.5043. [PMID: 33283304] - Brian A Lanman, Jennifer R Allen, John G Allen, Albert K Amegadzie, Kate S Ashton, Shon K Booker, Jian Jeffrey Chen, Ning Chen, Michael J Frohn, Guy Goodman, David J Kopecky, Longbin Liu, Patricia Lopez, Jonathan D Low, Vu Ma, Ana E Minatti, Thomas T Nguyen, Nobuko Nishimura, Alexander J Pickrell, Anthony B Reed, Youngsook Shin, Aaron C Siegmund, Nuria A Tamayo, Christopher M Tegley, Mary C Walton, Hui-Ling Wang, Ryan P Wurz, May Xue, Kevin C Yang, Pragathi Achanta, Michael D Bartberger, Jude Canon, L Steven Hollis, John D McCarter, Christopher Mohr, Karen Rex, Anne Y Saiki, Tisha San Miguel, Laurie P Volak, Kevin H Wang, Douglas A Whittington, Stephan G Zech, J Russell Lipford, Victor J Cee. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors.
Journal of medicinal chemistry.
2020 01; 63(1):52-65. doi:
10.1021/acs.jmedchem.9b01180. [PMID: 31820981]
