tilpisertib   Click here for help

GtoPdb Ligand ID: 12094

Synonyms: GS 4875 | GS-4875
Compound class: Synthetic organic
Comment: Tilpisertib (GS-4875) is an inhibitor of the serine/ threonine kinase Cot (a.k.a. MAP3K8/TPL2). It was developed by Gilead Sciences as a potential anti-inflammatory drug to treat auto-inflammatory diseases. The chemical structure is amongst those that are claimed as Cot (a.k.a. MAP3K8/TPL2) modulators in patent WO2020252151A1 [1]. Inhibition of Cot (which is an upstream regulator in the MEK-ERK pathway) is expected to reduce production and signalling of TNFα. Gilead's development pipeline now contains a TPL2 inhibitor, GS-5290, that is in phase 1 for inflammatory bowel disease. GS-5290 may be follow-up lead compound tilpisertib fosmecarbil.

tilpisertib is commercially available from our sponsors

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 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 113.45
Molecular weight 592.25
XLogP 6.15
No. Lipinski's rules broken 1

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 N#Cc1cnc2c(c1NCC(C)(C)C)cc(cc2Cl)N[C@@H](c1cccc2c1ccn(c2=O)C)c1nnn(c1)C12CC(C1)C2
Isomeric SMILES CC(C)(C)CNc1c2cc(cc(c2ncc1C#N)Cl)N[C@@H](c1cccc2c1ccn(c2=O)C)c1cn(nn1)C12CC(C1)C2
InChI InChI=1S/C33H33ClN8O/c1-32(2,3)18-37-28-20(15-35)16-36-29-25(28)10-21(11-26(29)34)38-30(27-17-42(40-39-27)33-12-19(13-33)14-33)23-6-5-7-24-22(23)8-9-41(4)31(24)43/h5-11,16-17,19,30,38H,12-14,18H2,1-4H3,(H,36,37)/t19?,30-,33?/m0/s1
InChI Key VFGSKBLZRDRHOI-ZAGPDIDGSA-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/)
No information available.
Summary of Clinical Use Click here for help
A phase 2 trial of tilpisertib in patients with ulcerative colitis has been completed, but results have not yet been published (August 2022).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04130919 Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis Phase 2 Interventional Gilead Sciences