Adagrasib – Mechanism of Action and Synthesis

Adagrasib is a pharmaceutical approved by the FDA in 2022 for the treatment of non-small cell lung cancer.
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Therapeutic area: oncology
Disease: NSCLC
Target: KRASG12C
Mechanism of Action: Covalent inhibitor, allosteric inhibitor.
RoA: PO
Chemistry section: Retrosynthesis & Forward Synthesis
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References:

Mechanism of Action:
1. J Exp Clin Cancer Res 41, 27 (2022). https://doi.org/10.1186/s13046-021-02...
2. Science 351, 604-608 (2016). https://doi.org/10.1126/science.aad6204
3. Nature 503, 548–551 (2013). https://www.nature.com/articles/natur...

Synthesis:
1. Discovery route: J. Med. Chem. 2020, 63, 6679. Open access. https://doi.org/10.1021/acs.jmedchem....
2. Commercial route (Presented here): DOI: 10.26434/chemrxiv-2022-9b3s1. https://doi.org/10.26434/chemrxiv-202...
3. Improved route: Org. Lett. 2023, 25, 944. Open access. https://doi.org/10.1021/acs.orglett.2...
4. Deprotection with 2-mercaptoethanol: Org. Lett. 2022, 24, 3736.
https://doi.org/10.1021/acs.orglett.2...