MS154   Click here for help

GtoPdb Ligand ID: 10635

Synonyms: compound 10 [PMID: 31895569]
Compound class: Synthetic organic
Comment: MS154 is a PROTAC (proteolysis targeting chimera). It is a hybrid molecule that simultaneously inhibits EGFR kinase activity and targets EGFR for destruction via ubiquitination and proteasomal degradation [2]. The kinase inhibitor portion of the molecule is derived from the first generation EGFR inhibitor gefitinib and it uses a cereblon (CRBN) ligand to engage the E3 ligase system.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 13
Hydrogen bond donors 3
Rotatable bonds 23
Topological polar surface area 184.63
Molecular weight 900.37
XLogP 5.08
No. Lipinski's rules broken 3
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Canonical SMILES COc1cc2ncnc(c2cc1OCCCN1CCN(CC1)CCC(=O)NCCCCCCCCOc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)Nc1ccc(c(c1)Cl)F
Isomeric SMILES COc1cc2ncnc(c2cc1OCCCN1CCN(CC1)CCC(=O)NCCCCCCCCOc1cccc2c1C(=O)N(C2=O)C1CCC(=O)NC1=O)Nc1ccc(c(c1)Cl)F
InChI InChI=1S/C46H54ClFN8O8/c1-62-38-28-35-32(43(51-29-50-35)52-30-12-13-34(48)33(47)26-30)27-39(38)64-25-9-18-54-20-22-55(23-21-54)19-16-40(57)49-17-6-4-2-3-5-7-24-63-37-11-8-10-31-42(37)46(61)56(45(31)60)36-14-15-41(58)53-44(36)59/h8,10-13,26-29,36H,2-7,9,14-25H2,1H3,(H,49,57)(H,50,51,52)(H,53,58,59)
1. Burslem GM, Smith BE, Lai AC, Jaime-Figueroa S, McQuaid DC, Bondeson DP, Toure M, Dong H, Qian Y, Wang J et al.. (2018)
The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study.
Cell Chem Biol, 25 (1): 67-77.e3. [PMID:29129716]
2. Cheng M, Yu X, Lu K, Xie L, Wang L, Meng F, Han X, Chen X, Liu J, Xiong Y et al.. (2020)
Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders.
J Med Chem, 63 (3): 1216-1232. DOI: 10.1021/acs.jmedchem.9b01566 [PMID:31895569]