MS432   Click here for help

GtoPdb Ligand ID: 10563

Synonyms: compound 23 [PMID: 31730343] | MS-432
Compound class: Synthetic organic
Comment: MS432 is the first-reported mitogen-activated protein kinase kinase 1/2 (MEK1/2) degrader [1]. Structurally MS432 is a hybrid molecule, combining a kinase-targeting ligand (based on mirdametinib) with a VHL-engaging moeity In this case VHL ligand 2, (S,R,S)-AHPC-Me . These types of agents are known as PROTACs, or proteolysis targeting chimeras. It targets the kinases for VHL E3 ligase- and proteasome-mediated degradation. In vitro, the effect of MS432 is phenocopied by MEK1/2 knockdown. MS432 is bioavailable and suitable for in vivo studies.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 11
Hydrogen bond donors 6
Rotatable bonds 30
Topological polar surface area 202.26
Molecular weight 1075.37
XLogP 10.57
No. Lipinski's rules broken 4
SMILES / InChI / InChIKey
Click here for help
Canonical SMILES OC1CC(N(C1)C(=O)C(C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)c1ccc(c(c1Nc1ccc(cc1F)I)F)F)C(=O)NC(c1ccc(cc1)c1scnc1C)C
Isomeric SMILES O[C@@H]1C[C@H](N(C1)C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)c1ccc(c(c1Nc1ccc(cc1F)I)F)F)C(=O)N[C@H](c1ccc(cc1)c1scnc1C)C
InChI InChI=1S/C50H65F3IN7O6S/c1-31(33-16-18-34(19-17-33)45-32(2)56-30-68-45)57-48(65)41-28-36(62)29-61(41)49(66)46(50(3,4)5)59-42(63)15-12-10-8-6-7-9-11-13-24-55-25-14-26-67-60-47(64)37-21-22-38(51)43(53)44(37)58-40-23-20-35(54)27-39(40)52/h16-23,27,30-31,36,41,46,55,58,62H,6-15,24-26,28-29H2,1-5H3,(H,57,65)(H,59,63)(H,60,64)/t31-,36+,41-,46+/m0/s1
InChI Key KCBAMQOKOLXLOX-BSZYMOERSA-N