CA-4948   

GtoPdb Ligand ID: 10152

Synonyms: AU-4948 | AU4948 | CA4948 | example 1 [WO2015104688A1]
Compound class: Synthetic organic
Comment: CA-4948 is an orally available, reversible inhibitor of interleukin 1 receptor associated kinase 4 (IRAK4) . It downmodulates the IRAK4 kinase activity that is required for toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling 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) [2]. 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.
Although not formally disclosed in a peer-reviewed publication, the structure presented here is that claimed as Example 1 in Aurigene Discovery Technologies' IRAK4 inhibitor patent WO2015104688A1 [3]. Data presented in scientific meeting abstract form indicates that CA-4948 demonstrates preclinical antitumour activity in in vitro and in vivo models [1].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 132.29
Molecular weight 417.15
XLogP 1.6
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES Nc1ccc(cn1)c1cccc(n1)C(=O)Nc1cnc2c(c1)oc(n2)N1CCOCC1
Isomeric SMILES Nc1ccc(cn1)c1cccc(n1)C(=O)Nc1cnc2c(c1)oc(n2)N1CCOCC1
InChI InChI=1S/C21H19N7O3/c22-18-5-4-13(11-23-18)15-2-1-3-16(26-15)20(29)25-14-10-17-19(24-12-14)27-21(31-17)28-6-8-30-9-7-28/h1-5,10-12H,6-9H2,(H2,22,23)(H,25,29)
InChI Key RWIMETUXCNDSLE-UHFFFAOYSA-N
Classification
Compound class Synthetic organic
IUPAC Name
6-(6-aminopyridin-3-yl)-N-(2-morpholin-4-yl-[1,3]oxazolo[4,5-b]pyridin-6-yl)pyridine-2-carboxamide
Synonyms
AU-4948 | AU4948 | CA4948 | example 1 [WO2015104688A1]
Database Links
GtoPdb PubChem SID 381118862
PubChem CID 118224238
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