TAK-981   Click here for help

GtoPdb Ligand ID: 11305

Synonyms: Example 133 [WO2016004136A1] | I-263a [WO2016004136A1] | subasumstat (proposed INN) | TAK981
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: TAK-981 is an inhibitor of the protein post-translational modification, SUMOylation. SUMO is a small ubiquitin-like modifier that is attached to proteins by enzymes of the SUMOylation complex (sumo activating enzyme, SAE) [2], and its attachment regulates protein function. SUMOylation has emerged as an important pathway in oncogenic processes, making SAE an oncology drug target. TAK-981 inhibits SUMOylation and has been shown to induce anti-tumour immunity in preclinical models. The precise molecular target for TAK-981 has not been disclosed.
The chemical structure that was submitted to the WHO for the INN subasumstat is identical to the chemical structure of TAK-981 that is held by PubChem, and is claimed in patent WO2016004136A1 by a team from Millennium Pharmaceuticals.
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 CDK toolkit. 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 10
Hydrogen bond donors 4
Rotatable bonds 8
Topological polar surface area 193.15
Molecular weight 577.12
XLogP 0.9
No. Lipinski's rules broken 0
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.

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Canonical SMILES Clc1ccc2c(c1)[C@@H](NCC2)c1cc(sc1C)C(=O)c1cncnc1N[C@@H]1C[C@@H]([C@H](C1)O)COS(=O)(=O)N
Isomeric SMILES Clc1ccc2c(c1)[C@@H](NCC2)c1cc(sc1C)C(=O)c1cncnc1N[C@@H]1C[C@@H]([C@H](C1)O)COS(=O)(=O)N
InChI InChI=1S/C25H28ClN5O5S2/c1-13-18(23-19-7-16(26)3-2-14(19)4-5-29-23)9-22(37-13)24(33)20-10-28-12-30-25(20)31-17-6-15(21(32)8-17)11-36-38(27,34)35/h2-3,7,9-10,12,15,17,21,23,29,32H,4-6,8,11H2,1H3,(H2,27,34,35)(H,28,30,31)/t15-,17-,21+,23+/m1/s1
InChI Key LXRZVMYMQHNYJB-UNXOBOICSA-N
References
1. Duffey MO, England D, Freeze S, Hu Z, Langston SP, Mcintyre C, Mizutani H, Ono K, Xu H. (2016)
Heteroaryl compounds useful as inhibitors of sumo activating enzyme.
Patent number: WO2016004136A1. Assignee: Duffey MO, England D, Freeze S, Hu Z, Langston SP, Mcintyre C, Mizutani H, Ono K, Xu H. Priority date: 01/07/2014. Publication date: 07/01/2016.
2. Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT. (2001)
Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9.
J Biol Chem, 276 (38): 35368-74. [PMID:11451954]