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
No information available.
Summary of Clinical Use Click here for help
TAK-981 has advanced to clinical evaluation in solid tumours and hematological malignancies.COVID-19: As an extension arm of NCT03648372, TAK-981 will be tested in a subgroup of cancer study patients with COVID-19. Enrollment into this COVID arm ended at the beginning of October 2020.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04065555 Intratumoral Microdosing of TAK-981 in Head and Neck Cancer Early Phase 1 Interventional Presage Biosciences
NCT03648372 A Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of TAK-981 in Adult Participants With Advanced or Metastatic Solid Tumors or Relapsed/Refractory Hematologic Malignancies and in a Subset With Coronavirus Disease 2019 (COVID-19) Phase 1 Interventional Takeda
NCT04074330 A Study of TAK-981 in Combination With Rituximab in Participants With Relapsed/Refractory (r/r) CD20-positive (CD20+) Non-Hodgkin Lymphoma (NHL) Phase 1/Phase 2 Interventional Takeda
NCT04381650 A Safety and Efficacy Study of TAK-981 Plus Pembrolizumab in Participants With Select Advanced or Metastatic Solid Tumors Phase 1/Phase 2 Interventional Takeda