zilurgisertib   Click here for help

GtoPdb Ligand ID: 11888

Synonyms: Compound A [WO2021257532A1] | example 34 [US20210155606A1] | INCB-00928 | INCB00928
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. Name-to-structure was formally disclosed in early 2025 [3]. Zilurgisertib (INCB00928) is declared as an ATP-competitive, orally available and selective ALK2/ACVR1 inhibitor.

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 (e.g. by gain-of-function mutation ALK2R206H) 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 exploited for therapeutic potential in FOP and anemia arising from chronic kidney disease or myeloproliferative diseases.
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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

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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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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
InChI Key KPRPFTOLWQQUAV-OCVAFRRMSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
2-amino-N-(4-hydroxy-1-bicyclo[2.2.2]octanyl)-5-[4-[(1R,5S)-3-(oxan-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]phenyl]pyridine-3-carboxamide
International Nonproprietary Names Click here for help
INN number INN
12123 zilurgisertib
Synonyms Click here for help
Compound A [WO2021257532A1] | example 34 [US20210155606A1] | INCB-00928 | INCB00928
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
Search Google for chemical match using the InChIKey KPRPFTOLWQQUAV-OCVAFRRMSA-N
Search Google for chemicals with the same backbone KPRPFTOLWQQUAV
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Search PubMed titles/abstracts zilurgisertib
UniChem Compound Search for chemical match using the InChIKey KPRPFTOLWQQUAV-OCVAFRRMSA-N
UniChem Connectivity Search for chemical match using the InChIKey KPRPFTOLWQQUAV-OCVAFRRMSA-N

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MedChemExpress
Zilurgisertib (links to external site)
Cat. No. HY-145608