J. Med. Chem. | for new protein degradation molecules of KRAS mutations

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Recently, a PROTAC molecule ZZ151, which efficiently and selectively degrades SOS1, was published in the Journal of Medicinal Chemistry by Mingyue Zheng and his group from Shanghai Institute of Maternology, Chinese Academy of Sciences. ZZ151 could specifically and effectively induce the degradation of SOS1. It exhibited potent anti-proliferative activity against a wide range of KRAS mutant cancer cells, and demonstrated excellent anticancer activity in KRAS-G12D and G12V mutants.

1. Represents the molecul

2. Targets and indications
◆ Target: SOS1 protease degradation
◆ Indications: Cancers associated with KRAS mutations

3. Synthesis path

4. Biological activity
The DC50 value of ZZ151 was 15.7 nM, which could effectively degrade SOS1 protease in cells. ZZ151, which degrades SOS1 primarily through the VHL-dependent proteasomal degradation pathway, exhibits potent anti-proliferative activity against a wide range of KRAS-mutant cancer cells, and exhibits excellent anticancer activity in KRAS-G12D and G12V mutants.