Target KRas, Let's Fighting
Absolutely, Sotorasib (AMG 510) and MRTX849 are the first line KRAS inhibitors, kinds of company are following the target as well, we summarized the patent disclosed recently, maybe helpful you!
Kirsten rat sarcoma viral oncogene homolog (KRAS) is a proto-oncogene of the RAS-MAPK pathway. KRAS mutations are present in a variety of malignancies including lung, colorectal, and pancreatic cancer.
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KRAS mutations are found in 20%–30% of non-small cell lung cancer (NSCLC). KRASG12C is the most prevalent KRAS mutation, and has been identified in approximately 15 % of NSCLC.
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Compounds that inhibit KRas activity are still highly desirable and under investigation, including those that disrupt effectors such as guanine nucleotide exchange factors (e.g., see Sun et al., (2012) Agnew Chem int Ed Engl. 51(25):6140-6143 doi: 10.1002/anie201201358) as well recent advances in the covalent targeting of an allosteric pocket of KRas G12C (e.g., see Ostrem et al., (2013) Nature 503:548-551 and Fell et al., (2018) ACS Med. Chem. Lett. 9: 1230-1234). Clearly there remains a continued interest and effort to develop inhibitors of KRas, particularly inhibitors of activating KRas mutants, especially KRas G12D.
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KRAS G12C and KRAS G12D are the most promising target for controlling cancel. Sheet 1 summarized the patent disclosed about this target recently, all the core structure were listed in column 3.
Sheet 1: the patents disclosed recently about KRAS.
Interestingly, except the core structure, the substitutes on the top, bottom, left and right are similar, sheet 2 summarized the substitutes.
Sheet 2: the substitutes disclosed in the patent about KRAS.
Meanwhile, we find some interesting building blocks was used in the route, typically as below rout:
Scheme I building block synthesis I
Scheme II building block synthesis II
As a pharmaceutical intermediates Supplier, we could provide this scaffold intermediate products with high quality.