WD6305

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Ligands
WD6305

GtoPdb Ligand ID: 13110

Synonyms: compound 9 [PMID: 38194973] | WD-6305

Comment: WD6305 is a heterobifunctional degrader (PROTAC) that targets the RNA methyltransferase METTL3 [1]. It is intended to promote proteasomal degradation of the METTL3-METTL14 methyltransferase complex as an anti-leukemic strategy. The PROTAC engages the Hippel-Lindau (VHL) E3 ligase, and METTL3 is targeted by the small molecule inhibitor UZH2. WD6305 inhibits N⁶-methyladenosine (m⁶A) methylation of RNA, and has the effect of reducing proliferation of AML cells. It more efficiently reduces proliferation of AML cells than blocking METTL3 catalytic activity with UZH2.

2D Structure

Physico-chemical Properties

Hydrogen bond acceptors	16
Hydrogen bond donors	5
Rotatable bonds	19
Topological polar surface area	211.97
Molecular weight	1112.38
XLogP	4.86
No. Lipinski's rules broken	3

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

SMILES / InChI / InChIKey

Canonical SMILES	C[C@@H](C1=CC=C(C=C1)C2=C(C)N=CS2)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCC#CC4=CC=C(C=C4)CNC5=NC=NC(=C5)N6CCC7(CC6)CN(CC(=O)N7)C8=CC(=C(C=C8F)CN9CCC(C)(C)CC9)F)O
Isomeric SMILES	C[C@H](NC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@@H](NC(=O)CCC#CC2=CC=C(CNC3=CC(=NC=N3)N4CCC5(CC4)CN(CC(=O)N5)C6=C(F)C=C(CN7CCC(C)(C)CC7)C(F)=C6)C=C2)C(C)(C)C)C8=CC=C(C=C8)C9=C(C)N=CS9
InChI	InChI=1S/C61H75F2N11O5S/c1-39(43-16-18-44(19-17-43)55-40(2)67-38-80-55)68-57(78)50-29-46(75)34-74(50)58(79)56(59(3,4)5)69-53(76)11-9-8-10-41-12-14-42(15-13-41)32-64-51-31-52(66-37-65-51)72-26-22-61(23-27-72)36-73(35-54(77)70-61)49-30-47(62)45(28-48(49)63)33-71-24-20-60(6,7)21-25-71/h12-19,28,30-31,37-39,46,50,56,75H,9,11,20-27,29,32-36H2,1-7H3,(H,68,78)(H,69,76)(H,70,77)(H,64,65,66)/t39-,46+,50-,56+/m0/s1
InChI Key	FTIPAFFEWGMNDM-LZZSXEHKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)