MS8709   Click here for help

GtoPdb Ligand ID: 13288

Synonyms: Compound 10 [PMID: 38464025] [1] | MS-8709
Compound class: Synthetic organic
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
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
Bioactivity Comments
MS8709 promotes degradation of G9a and GLP proteins with in vitro DC50 values of 260 nM and 274 nM respectively. It is bioavailable in mice so is suitable for in vivo studies.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
euchromatic histone lysine methyltransferase 1 Hs Inhibitor Inhibition - - - 1
⤷ [1]
euchromatic histone lysine methyltransferase 2 Hs Inhibitor Inhibition - - - 1
⤷ [1]