emavusertib   Click here for help

GtoPdb Ligand ID: 10152

Synonyms: AU-4948 | AU4948 | CA4948 | compound 24 [PMID: 33335659]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: CA-4948 is an orally available, reversible inhibitor of interleukin 1 receptor associated kinase 4 (IRAK4) [2]. It downmodulates the IRAK4 activity that is required for Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signalling in a variety of myeloid and lymphoid cell types, notably in cancer cells (e.g. diffuse large B-cell lymphoma cells) in which the MYD88 adaptor protein carries an activating mutation (MYD88L265P) [1]. In such mutant cells NF-κB signaling is constitutively active and this is indicative of a poorer prognosis. Hence, IRAK4 inhibitors such as CA-4948 are expected to provide clinical benefit in MYD88 mutation +ve hematological cancers. The chemical structure of CA-4948 matches that submitted to the WHO for the INN emavusertib.
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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 10
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 142.88
Molecular weight 491.19
XLogP 1.78
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 O[C@@H]1CCN(C1)c1nc2nc(oc2cc1NC(=O)c1coc(n1)c1ccnc(c1)C)N1CCOCC1
Isomeric SMILES O[C@@H]1CCN(C1)c1nc2nc(oc2cc1NC(=O)c1coc(n1)c1ccnc(c1)C)N1CCOCC1
InChI InChI=1S/C24H25N7O5/c1-14-10-15(2-4-25-14)23-27-18(13-35-23)22(33)26-17-11-19-20(28-21(17)31-5-3-16(32)12-31)29-24(36-19)30-6-8-34-9-7-30/h2,4,10-11,13,16,32H,3,5-9,12H2,1H3,(H,26,33)/t16-/m1/s1
InChI Key SJHNWSAWWOAWJH-MRXNPFEDSA-N
References
1. Booher RN, Nowakowski GS, Patel K, Lunning MA, Samson MES, Atoyan R, Ma AW, Xu G-X, Dellarocca S, Modafferi H et al.. (2018)
Preclinical Activity of IRAK4 Kinase Inhibitor CA-4948 Alone or in Combination with Targeted Therapies and Preliminary Phase 1 Clinical Results in Non-Hodgkin Lymphoma.
Blood, 132 (Supplement 1): 4168 Meeting poster. DOI: 10.1182/blood-2018-99-117383
2. Gummadi VR, Boruah A, Ainan BR, Vare BR, Manda S, Gondle HP, Kumar SN, Mukherjee S, Gore ST, Krishnamurthy NR et al.. (2020)
Discovery of CA-4948, an Orally Bioavailable IRAK4 Inhibitor for Treatment of Hematologic Malignancies.
ACS Med Chem Lett, 11 (12): 2374-2381. [PMID:33335659]