MS8709

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Ligands
MS8709

GtoPdb Ligand ID: 13288

Synonyms: Compound 10 [PMID: 38464025] [1] | MS-8709

Comment: MS8709 is a first-in-class G9a/GLP PROTAC degrader whose structure was disclosed in preprint [1]. Note that in this context G9a and GLP are histone lysine methyltransferases encoded by EHMT2 and EHMT1 respectively. Excessive activation of the G9a/GLP axis promotes cancer progression, survival, and metastasis, making these targets for oncology drug development. Interaction with the target proteins is achieved by inclusion of the UNC0642 parent inhibitor, and this is linked to a von Hippel Lindau (VHL)-binding moiety to engage with the E3 ligase.

2D Structure

Physico-chemical Properties

Hydrogen bond acceptors	18
Hydrogen bond donors	5
Rotatable bonds	36
Topological polar surface area	230.43
Molecular weight	1200.57
XLogP	7.52
No. Lipinski's rules broken	4

SMILES / InChI / InChIKey

Canonical SMILES	CC1=C(C2=CC=C(C=C2)CNC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCCNC(=O)CCCN4CCC(CC4)NC5=C6C=C(C(=CC6=NC(=N5)N7CCC(CC7)(F)F)OCCCN8CCCC8)OC)O)SC=N1
Isomeric SMILES	FC1(CCN(CC1)C2=NC3=CC(=C(C=C3C(=N2)NC4CCN(CC4)CCCC(=O)NCCCCCCCCCCCC(=O)N[C@H](C(=O)N5[C@@H](C[C@H](C5)O)C(=O)NCC6=CC=C(C=C6)C7=C(N=CS7)C)C(C)(C)C)OC)OCCCN8CCCC8)F
InChI	InChI=1S/C64H95F2N11O7S/c1-45-57(85-44-69-45)47-23-21-46(22-24-47)42-68-60(81)52-39-49(78)43-77(52)61(82)58(63(2,3)4)72-56(80)19-13-11-9-7-6-8-10-12-14-29-67-55(79)20-17-32-75-34-25-48(26-35-75)70-59-50-40-53(83-5)54(84-38-18-33-74-30-15-16-31-74)41-51(50)71-62(73-59)76-36-27-64(65,66)28-37-76/h21-24,40-41,44,48-49,52,58,78H,6-20,25-39,42-43H2,1-5H3,(H,67,79)(H,68,81)(H,72,80)(H,70,71,73)/t49-,52+,58-/m1/s1
InChI Key	CLUWNSLFLMBFKA-RMCUFUCFSA-N