foselutoclax   Click here for help

GtoPdb Ligand ID: 13366

Synonyms: UBX-1325 | UBX1325
Compound class: Synthetic organic
Comment: Foselutoclax (UBX1325) is a small-molecule inhibitor of BCL-xL that has a senolytic action [2]. Pharmacological elimination of senescent cells is a mechanism that is under investigation to treat pathologies that are promoted in the presence of senescent cells. This senolytic strategy is considered to be an alternative to anti-vascular endothelial growth factor therapies such as aflibercept in degenerative edematous retinal conditions (e.g. diabetic retinopathy) [3].

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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 21
Topological polar surface area 261.23
Molecular weight 1159.69
XLogP 6.88
No. Lipinski's rules broken 4

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 CC(C)N1C(=C(C(=C1C2=CC=C(C=C2)Cl)C3=CC=CC(=C3)N4CCN(CC4)C5=CC=C(C=C5)NS(=O)(=O)C6=CC=C(C(=C6)S(=O)(=O)C(F)(F)F)N[C@H](CCN7CCC(CC7)OP(=O)(O)O)CSC8=CC=CC=C8)C(=O)O)C
Isomeric SMILES CC1=C(C(=C(N1C(C)C)C2=CC=C(C=C2)Cl)C3=CC(=CC=C3)N4CCN(CC4)C5=CC=C(C=C5)NS(=O)(=O)C6=CC(=C(C=C6)N[C@H](CCN7CCC(CC7)OP(=O)(O)O)CSC8=CC=CC=C8)S(=O)(=O)C(F)(F)F)C(=O)O
InChI InChI=1S/C53H59ClF3N6O10PS3/c1-35(2)63-36(3)49(52(64)65)50(51(63)37-12-14-39(54)15-13-37)38-8-7-9-43(32-38)62-30-28-61(29-31-62)42-18-16-40(17-19-42)59-77(71,72)46-20-21-47(48(33-46)76(69,70)53(55,56)57)58-41(34-75-45-10-5-4-6-11-45)22-25-60-26-23-44(24-27-60)73-74(66,67)68/h4-21,32-33,35,41,44,58-59H,22-31,34H2,1-3H3,(H,64,65)(H2,66,67,68)/t41-/m1/s1
InChI Key FSZILRQCEAUYPL-VQJSHJPSSA-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/)
Bioactivity Comments
In vivo, intravitreal administration of UBX-1325 reduces the abundance of anti-apoptotic Bcl-xL:Bim complexes in the retinas of oxygen induced retinopathy (OIR) model mice [5].
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Bcl-2-like 1 Hs Antagonist Antagonist - - - 2
⤷ [2]
Targets where the ligand is described in the comment field
Target Comment
Bcl-2-like 1 The longer protein isoform generated from the BCL2L1 gene, Bcl-xL, acts as an apoptotic inhibitor (anti-death protein) whilst the shorter form, Bcl-xS, acts as an apoptotic activator [1]. Bcl-xL is abundant in senescent cells that are linked to the production of pro-inflammatory mediators. This overabundance of pro-inflammatory mediators with aging correlates with diseases such as osteoporosis, diabetes, heart disease, kidney disease and Alzheimer's disease. Due to its role in enabling the survival of senescent cells Bcl-xL is being pursued as a target for the development of senolytic agents for the treatment of age-related diseases (for example foselutoclax) [2,4].