zilurgisertib   Click here for help

GtoPdb Ligand ID: 11888

Synonyms: Compound A [WO2021257532A1] | example 34 [US20210155606A1]
Compound class: Synthetic organic
Comment: The chemical structure for zilurgisertib was revealed in WHO proposed INN list 126 (Jan 2022), in which it was described as a serine/threonine kinase inhibitor. It is one of the compounds that are claimed in Novartis' ALK2 (ACVR1) inhibitor patent US20210155606A1 [1], and it is also claimed in WO2021257532A1 by Incyte as "Compound A" [2]. Incyte have declared an ALK2 inhibitor (INCB00928) in their development pipeline, but the name-to-structure has not been formally disclosed.

ALK2/ACVR1 is a serine/threonine protein kinase receptor for type I bone morphogenic protein (BMP), and this signalling pathway is crucial in bone formation, and hyperactivty of the pathway is associated with diseases that are characterised by bone malformation, such as fibrodysplasia ossificans progressiva (FOP). ALK2 is also involved in the maintenance of iron homeostasis by governing production of the iron regulatory hormone hepcidin. Elevated hepcidin is thought to be a powerful driver of the pathophysiology of anemia that's associated with chronic disease. Inhibition of ALK2 upstream of hepcidin should increase circulating iron levels. Thus direct inhibition of ALK2/ACVR1 is a molecular mechanism that is being expolited for therapeutic potential in FOP and anemia arising from chronic kidney disease or myeloproliferative diseases.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 100.71
Molecular weight 502.29
XLogP 3.62
No. Lipinski's rules broken 0
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Canonical SMILES O=C(c1cc(cnc1N)c1ccc(cc1)[C@@]12CN(C[C@H]2C1)C1CCOCC1)NC12CCC(CC1)(CC2)O
Isomeric SMILES Nc1ncc(cc1C(=O)NC12CCC(CC1)(CC2)O)c1ccc(cc1)[C@]12CN(C[C@H]1C2)C1CCOCC1
InChI InChI=1S/C30H38N4O3/c31-26-25(27(35)33-28-7-10-29(36,11-8-28)12-9-28)15-21(17-32-26)20-1-3-22(4-2-20)30-16-23(30)18-34(19-30)24-5-13-37-14-6-24/h1-4,15,17,23-24,36H,5-14,16,18-19H2,(H2,31,32)(H,33,35)/t23-,28?,29?,30+/m1/s1
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
International Nonproprietary Names Click here for help
INN number INN
12123 zilurgisertib
Synonyms Click here for help
Compound A [WO2021257532A1] | example 34 [US20210155606A1]
Database Links Click here for help
BindingDB Ligand 451802
CAS Registry No. 2173389-57-4 (source: WHO INN record)
GtoPdb PubChem SID 461663444
PubChem CID 138628908
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