Bond, Michael J.’s team published research in ACS Central Science in 6 | CAS: 2502156-03-6

ACS Central Science published new progress about 2502156-03-6. 2502156-03-6 belongs to piperazines, auxiliary class PROTACs,K-Ras (G12C)/PROTAC, name is (2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-Chloronaphthalen-1-yl)-4-((S)-3-(cyanomethyl)-4-(2-fluoroacryloyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)oxy)methyl)pyrrolidin-1-yl)propoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide, and the molecular formula is C59H71ClFN11O7S, Application In Synthesis of 2502156-03-6.

Bond, Michael J. published the artcileTargeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs, Application In Synthesis of 2502156-03-6, the publication is ACS Central Science (2020), 6(8), 1367-1375, database is CAplus and MEDLINE.

KRAS is mutated in ~20% of human cancers and is one of the most sought-after targets for pharmacol. modulation, despite having historically been considered “undruggable.” The discovery of potent covalent inhibitors of the KRASG12C mutant in recent years has sparked a new wave of interest in small mols. targeting KRAS. While these inhibitors have shown promise in the clinic, we wanted to explore PROTAC-mediated degradation as a complementary strategy to modulate mutant KRAS. Herein, we report the development of LC-2(I), the first PROTAC capable of degrading endogenous KRASG12C. LC-2 covalently binds KRASG12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRASG12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRASG12C cell lines. LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells. KRAS is one of the most sought-after targets for cancer therapy. Herein, we report the development of LC-2, the first PROTAC capable of inducing endogenous KRASG12C degradation by recruiting VHL.

ACS Central Science published new progress about 2502156-03-6. 2502156-03-6 belongs to piperazines, auxiliary class PROTACs,K-Ras (G12C)/PROTAC, name is (2S,4R)-1-((S)-2-(3-(3-((S)-2-(((7-(8-Chloronaphthalen-1-yl)-4-((S)-3-(cyanomethyl)-4-(2-fluoroacryloyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)oxy)methyl)pyrrolidin-1-yl)propoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide, and the molecular formula is C59H71ClFN11O7S, Application In Synthesis of 2502156-03-6.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics