MS15   Click here for help

GtoPdb Ligand ID: 12216

Synonyms: compound 62 [PMID: 36197750]
Compound class: Synthetic organic
Comment: MS15 is a PROTAC that targets the AKT serine/threonine kinases for proteasomal degradation [1]. Its AKT binding domain is the allosteric pan-AKT inhibitor miransertib (ARQ-092). This is joined to a von Hippel-Lindau (VHL)-recruiting ligand by a short linker. MS15 selectively and significantly degrades AKT1 and AKT2 and suppresses proliferation in cancer cells with KRAS/BRAF mutations. AKT3 is expressed at very low levels in the SW620 cells used in the assay, so the degrading effect of MS15 on AKT3 is unclear. An earlier AKT-directed PROTAC (MS21) with an ATP-competitive AKT inhibitor (capivasertib/AZD5363) as warhead was not anti-proliferative against KRAS/BRAF mutation-carrying cells.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 15
Hydrogen bond donors 6
Rotatable bonds 29
Topological polar surface area 264.09
Molecular weight 1114.45
XLogP 10.29
No. Lipinski's rules broken 5
SMILES / InChI / InChIKey
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Canonical SMILES O=C(CCc1cccc(c1)c1ccc2c(n1)n(c1ccc(cc1)C1(N)CCC1)c(n2)c1cccnc1N)NCCCCCCCCCCC(=O)N[C@@H](C(C)(C)C)C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@H](c1ccc(cc1)c1scnc1C)C)O
Isomeric SMILES O=C(NCCCCCCCCCCC(=O)N[C@@H](C(C)(C)C)C(=O)N1[C@H](C(=O)N[C@@H](C)c2ccc(c3c(C)ncs3)cc2)C[C@@H](O)C1)CCc1cc(c2nc3c(nc(c4c(N)nccc4)n3c3ccc(C4(N)CCC4)cc3)cc2)ccc1
InChI InChI=1S/C64H79N11O5S/c1-41(44-22-24-45(25-23-44)56-42(2)69-40-81-56)70-61(79)53-38-49(76)39-74(53)62(80)57(63(3,4)5)73-55(78)20-12-10-8-6-7-9-11-13-35-67-54(77)32-21-43-17-14-18-46(37-43)51-30-31-52-60(71-51)75(59(72-52)50-19-15-36-68-58(50)65)48-28-26-47(27-29-48)64(66)33-16-34-64/h14-15,17-19,22-31,36-37,40-41,49,53,57,76H,6-13,16,20-21,32-35,38-39,66H2,1-5H3,(H2,65,68)(H,67,77)(H,70,79)(H,73,78)/t41-,49+,53-,57+/m0/s1
InChI Key XYGBNRINQSQNJG-IQDHSYJRSA-N
Classification Click here for help
Compound class Synthetic organic
Ligand families/groups PROTACs, molecular glues and other degraders
Synonyms Click here for help
compound 62 [PMID: 36197750]
Database Links Click here for help
GtoPdb PubChem SID 472319336
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UniChem Connectivity Search for chemical match using the InChIKey XYGBNRINQSQNJG-IQDHSYJRSA-N