2502156-03-6
Chemical Structure
LC-2
- CAS No.: 2502156-03-6
- Formula:C59H71ClFN11O7S
- Molecular Weight:1132.78
IUPAC Name: (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
InChIKey: ZCGQZLKPUVGCBQ-HLMPTVQRSA-N
SMILES: O=C(NCC1=CC=C(C=C1)C2=C(N=CS2)C)[C@H]3N(C[C@@H](C3)O)C([C@H](C(C)(C)C)NC(CCOCCCN4[C@@H](CCC4)COC5=NC(N6C[C@@H](N(CC6)C(C(F)=C)=O)CC#N)=C7C(CN(CC7)C8=C9C(Cl)=CC=CC9=CC=C8)=N5)=O)=O
Biological Activity: LC-2 is an orally active PROTAC-class degrader targeting KRASG12C and a MAPK inhibitor. LC-2 shows higher selectivity for KRASG12C than wild-type KRAS and other KRAS mutants. LC-2 covalently binds to KRASG12C via the MRTX849 (HY-130149) warhead, recruits the VHL E3 ligase to form a ternary complex, and induces ubiquitination and degradation of KRASG12C. Meanwhile, LC-2 inhibits the MAPK signaling pathway, reduces the phosphorylation levels of CRAF and AKT, thereby inducing apoptosis and suppressing cancer cell and tumor growth. LC-2 can be used for the research of KRASG12C-positive cancers, including non-small cell lung cancer and colorectal cancer[1][2][3].
| Cat. No. | Product Name | Purity | Description | Pricing | |||||||||||||||||||
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LC-2 | 98.48% | LC-2 is an orally active PROTAC-class degrader targeting KRASG12C and a MAPK inhibitor. LC-2 shows higher selectivity for KRASG12C than wild-type KRAS and other KRAS mutants. LC-2 covalently binds to KRASG12C via the MRTX849 (HY-130149) warhead, recruits the VHL E3 ligase to form a ternary complex, and induces ubiquitination and degradation of KRASG12C. Meanwhile, LC-2 inhibits the MAPK signaling pathway, reduces the phosphorylation levels of CRAF and AKT, thereby inducing apoptosis and suppressing cancer cell and tumor growth. LC-2 can be used for the research of KRASG12C-positive cancers, including non-small cell lung cancer and colorectal cancer. | ||||||||||||||||||||
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References
- [1]. Bond MJ, et al. Targeted Degradation of Oncogenic KRAS by VHL-Recruiting PROTACs. ACS central science. 2020 Aug 26;6(8):1367-1375. [Content Brief]
- [2]. Kurimchak AM, et al. The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells. Science signaling. 2022 Aug 30;15(749):eabn2707. [Content Brief]
- [3]. Yang J, et al. A pan-KRAS degrader for the treatment of KRAS-mutant cancers. Cell discovery. 2024 Jun 28;10(1):70. [Content Brief]
