MCB-36

MCB-36 is a VHL-recruiting pan-KRAS PROTAC degrader without affecting KRAS transcription. MCB-36 exhibits minimal effects on HRAS and NRAS protein levels. MCB-36 binds to the GDP-loaded state of G12D, G12C, G12V, and wild-type KRAS with high affinities Kd ≈ 1 pM) . MCB-36 decreases p-ERK levels, leading to cell apoptosis. MCB-36 effectively suppress KRASG12C inhibitor-resistant cancer cells and remodel the tumor immune microenvironment. MCB-36 can be used for the study of colorectal cancer and lung cancer (Pink: Target protein ligand; Blue: E3 ligand (HY-112078) ; Black: Linker (HY-W091879) ) [1].

Product Specifications

UNSPSC

12352005

Target

Apoptosis; Caspase; p38 MAPK; PERK; PROTACs; Ras; TNF Receptor

Related Pathways

Apoptosis; Cell Cycle/DNA Damage; GPCR/G Protein; MAPK/ERK Pathway; PROTAC

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Smiles

C#CC1=C(C=CC2=CC(O)=CC(C3=NC=C4C(N5CCC[C@@](O)(C5)C)=NC(OC[C@@H]6CCCN6CCCCCCC(N[C@@H](C(C)(C)C)C(N7C[C@@H](C[C@H]7C(N[C@H](C8=CC=C(C=C8)C9=C(N=CS9)C)C)=O)O)=O)=O)=NC4=C3F)=C21)F

Molecular Formula

C60H71F2N9O7S

Molecular Weight

1100.32

References & Citations

[1]Feng J, et al. A pan-KRAS inhibitor and its derived degrader elicit multifaceted anti-tumor efficacy in KRAS-driven cancers. Cancer Cell. 2025 Jul 25:S1535-6108 (25) 00310-1.