LC-2

LC-2 is a potent and first-in-class von Hippel-Lindau-based PROTAC capable of degrading endogenous KRAS G12C, with DC50s between 0.25 and 0.76 μM[1]. LC-2 covalently binds KRAS G12C with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS G12C degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS G12C cell lines[2].

Product Specifications

CAS Number

[2502156-03-6]

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

PROTACs; Ras

Type

Reference compound

Related Pathways

GPCR/G Protein; MAPK/ERK Pathway; PROTAC

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/protac-krasg12c-degrader-lc-2.html

Purity

98.48

Solubility

DMSO : 100 mg/mL (ultrasonic)

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

Molecular Formula

C59H71ClFN11O7S

Molecular Weight

1132.78

Precautions

H302, H315, H319, H335

References & Citations

[1]De Vita E, et al. The Missing Link between (Un) druggable and Degradable KRAS. ACS Cent Sci. 2020;6 (8) :1281-1284.|[2]Bond MJ, et al. Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs. ACS Cent Sci. 2020;6 (8) :1367-1375.