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example 5 [WO2023245150]   Click here for help

GtoPdb Ligand ID: 14089

Compound class: Synthetic organic
Comment: This is one of the more potent compounds claimed in patent WO2023245150A1 (Prelude Therapeutics) as lysine acetyltransferase 6A (KAT6A) degraders [1]. It is a PROTAC heterobifunctional molecule with a thalidomide-based cereblon ubiquitin ligase binding moiety linked to a selective KAT6A binding ligand. It promotes formation of a ternary complex that directs KAT6A protein for proteosomal degradation. This mechanism is proposed as an alternative to direct enzyme inhibition.
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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Click here for structure editor
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 15
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 194.24
Molecular weight 847.94
XLogP 2.1
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 COC1=CC(=CC2=C1C(=NO2)NS(=O)(=O)C3=CC(=CC=C3)N4CC5(CCN(CC5)CC6CCN(C6)C7=CC=C8C(=C7)C(=O)N(C9CCC(=O)NC9=O)C8=O)C4)CN%10C=CC=N%10
Isomeric SMILES COC1=CC(CN2C=CC=N2)=CC3=C1C(NS(=O)(=O)C4=CC=CC(=C4)N5CC6(C5)CCN(CC7CCN(C7)C8=CC9=C(C=C8)C(=O)N(C%10CCC(=O)NC%10=O)C9=O)CC6)=NO3
InChI InChI=1S/C43H45N9O8S/c1-59-35-18-28(24-51-14-3-13-44-51)19-36-38(35)39(46-60-36)47-61(57,58)31-5-2-4-29(20-31)50-25-43(26-50)11-16-48(17-12-43)22-27-10-15-49(23-27)30-6-7-32-33(21-30)42(56)52(41(32)55)34-8-9-37(53)45-40(34)54/h2-7,13-14,18-21,27,34H,8-12,15-17,22-26H2,1H3,(H,46,47)(H,45,53,54)
InChI Key XVJJGQFASNNHCT-UHFFFAOYSA-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/)
References
1. Pawley S, Buesking AW, Combs AP. (2023)
Kat6 targeting compounds with ubiquitin ligase binding moiety.
Patent number: WO2023245150A1. Assignee: Prelude Therapeutics Incorporated. Priority date: 16/06/2023. Publication date: 21/12/2023.