WD6305   Click here for help

GtoPdb Ligand ID: 13110

Synonyms: compound 9 [PMID: 38194973] | WD-6305
Compound class: Synthetic organic
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
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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 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/). 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 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
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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.

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/)

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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/)
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Canonical SMILES Download
Isomeric SMILES Download
InChI standard identifier Download
InChI standard key Download

Molecular structure representations generated using Open Babel