nemtabrutinib   Click here for help

GtoPdb Ligand ID: 11413

Synonyms: ARQ-531 | ARQ531 | ArQule 531 | MK-1026 | MK1026
PDB Ligand
Compound class: Synthetic organic
Comment: Nemtabrutinib (ARQ-531) is a reversible, ATP-competitive kinase inhibitor, that was originally designed to inhibit Bruton tyrosine kinase (BTK) [2]. It does not interact with BTK's catalytic domain Cys481 so may not be susceptible to resistance conferred by mutation of this residue. This is in contrast to ibrutinib, which is sensitive to alterations at Cys481. Nemtabrutinib has inhibitory activities against a range of other TEC family kinases, as well as Src and Trk kinases [1-2]. This non-selective activity is believed to contribute to nemtabrutinib's efficacy against chronic lymphocytic leukemia cells.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 6
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 109.36
Molecular weight 478.14
XLogP 4.67
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 OC[C@@H]1CC[C@H](CO1)Nc1ncnc2c1c(c[nH]2)C(=O)c1ccc(cc1Cl)Oc1ccccc1
Isomeric SMILES OC[C@@H]1CC[C@H](CO1)Nc1ncnc2c1c(c[nH]2)C(=O)c1ccc(cc1Cl)Oc1ccccc1
InChI InChI=1S/C25H23ClN4O4/c26-21-10-17(34-16-4-2-1-3-5-16)8-9-19(21)23(32)20-11-27-24-22(20)25(29-14-28-24)30-15-6-7-18(12-31)33-13-15/h1-5,8-11,14-15,18,31H,6-7,12-13H2,(H2,27,28,29,30)/t15-,18+/m1/s1
InChI Key JSFCZQSJQXFJDS-QAPCUYQASA-N
References
1. Elgamal OA, Mehmood A, Jeon JY, Carmichael B, Lehman A, Orwick SJ, Truxall J, Goettl VM, Wasmuth R, Tran M et al.. (2020)
Preclinical efficacy for a novel tyrosine kinase inhibitor, ArQule 531 against acute myeloid leukemia.
J Hematol Oncol, 13 (1): 8. [PMID:31992353]
2. Reiff SD, Mantel R, Smith LL, Greene JT, Muhowski EM, Fabian CA, Goettl VM, Tran M, Harrington BK, Rogers KA et al.. (2018)
The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter Transformation.
Cancer Discov, 8 (10): 1300-1315. [PMID:30093506]