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BMS-986458   Click here for help

GtoPdb Ligand ID: 13838

Compound class: Synthetic organic
Comment: BMS-986458 is an orally bioavailable bifunctional degrader molecule that is designed to target the BCL6 transcription factor in B-cell lymphomas [1]. It promotes CRL4CRBN E3 ubiquitin ligase-dependent dagradation of the BCL6 protein. The chemical structure was disclosed during the 'First Time disclosures' session at the ACS Spring 2025 meeting in San Diego. This matches one of the compounds claimed in patent WO2023212147A1 [2].
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 12
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 134.1
Molecular weight 628.13
XLogP 0.73
No. Lipinski's rules broken 2

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]1CN(CC[C@H]1NC2=CC3=C(C=C2)C(=NN3C)C4CCC(=O)NC4=O)C5=NC(=C(C=N5)Cl)NC6=CC=C7C(=C6)CC(=O)N7C
Isomeric SMILES C[C@@H]1CN(CC[C@H]1NC2=CC3=C(C=C2)C(=NN3C)C4CCC(=O)NC4=O)C5=NC=C(Cl)C(NC6=CC7=C(C=C6)N(C)C(=O)C7)=N5
InChI InChI=1S/C32H34ClN9O3/c1-17-16-42(32-34-15-23(33)30(38-32)36-19-5-8-25-18(12-19)13-28(44)40(25)2)11-10-24(17)35-20-4-6-21-26(14-20)41(3)39-29(21)22-7-9-27(43)37-31(22)45/h4-6,8,12,14-15,17,22,24,35H,7,9-11,13,16H2,1-3H3,(H,34,36,38)(H,37,43,45)/t17-,22?,24-/m1/s1
InChI Key JALIPZPFONOAJA-ZKGBLMBJSA-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. Groocock L, Deb G, Zhu J, Gamez J, Castiglioni P, Sanchez-Castillo M, Schumacher J, Benitez Rondan A, Jankeel D, Martinez-Garcia K et al.. (2024)
BMS-986458 a Potential First-in-Class, Highly Selective, Potent and Well Tolerated BCL6 Ligand Directed Degrader (LDD) Demonstrates Multi-Modal Anti-Tumor Efficacy for the Treatment of B-Cell Non-Hodgkin's Lymphoma.
Blood, 144 (Supplement 1): 957. DOI: 10.1182/blood-2024-210951
2. Huang D, Alexander MD, Whitefield BW, Shunatona HP, Dodd DS, Mortensen DS, Miseo G, Holmberg-Douglas N, Rhodes J, Griffin J. (2023)
Heterocyclic compounds as modulators of bcl6 as ligand directed degraders.
Patent number: WO2023212147A1. Assignee: Celgene Corporation, Bristol-Myers Squibb Company. Priority date: 27/04/2023. Publication date: 02/11/2023.