K-Ras ligand-Linker Conjugate 5

• CAT Number: I016929
• CAS Number: 2378261-85-7
• Molecular Formula: C42H59N7O8
• Molecular Weight: 789.96
• Purity: ≥95%
• Synonyms: tert-butyl (2S)-2-(cyanomethyl)-4-[2-[[(2S,4R)-4-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]-1-methylpyrrolidin-2-yl]methoxy]-7-naphthalen-1-yl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]piperazine-1-carboxylate
• InChI: InChI=1S/C42H59N7O8/c1-42(2,3)57-41(51)49-17-16-48(27-32(49)12-14-43)39-36-13-15-47(38-11-7-9-31-8-5-6-10-35(31)38)29-37(36)44-40(45-39)56-30-33-26-34(28-46(33)4)55-25-24-54-23-22-53-21-20-52-19-18-50/h5-11,32-34,50H,12-13,15-30H2,1-4H3/t32-,33-,34+/m0/s1
• InChIKey: YWJHMWJHKMFQGA-DHWXLLNHSA-N
• SMILES: CC(C)(C)OC(=O)N1CCN(CC1CC#N)C2=NC(=NC3=C2CCN(C3)C4=CC=CC5=CC=CC=C54)OCC6CC(CN6C)OCCOCCOCCOCCO

K-Ras ligand-Linker Conjugate 5 incorporates a ligand for K-Ras recruiting moiety, and a PROTAC linker, which recruit E3 ligases (such as VHL, CRBN, MDM2, and IAP). K-Ras ligand-Linker Conjugate 5 can be used in the synthesis of PROTAC K-Ras Degrader-1 (HY-129523), which is potent PROTAC K-Ras degrader that exhibits ≥70% degradation efficacy in SW1573 cells[1].
PROTACs contain two different ligands connected by a linker; one is a ligand for an E3 ubiquitin ligase and the other is for the target protein. PROTACs exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins[1].

Reference

[1]. CREW, Andrew P., et al. MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE. WO2019195609A2.