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zinilisib   Click here for help

GtoPdb Ligand ID: 14369

Synonyms: example 8 [WO2024054469A1]
Compound class: Synthetic organic
Comment: The chemical structure for this compound was obtained from WHO INN proposed list 134 (Feb 2026), in which it is described as a phosphatidylinositol 3-kinase (PI3K) inhibitor with antineoplastic potential. The structure is claimed in patent WO2024054469A1 (OnKure Inc) as example 8 [1]. OnKure's most advance PI3K inhibitor is OKI-219 which is selective for the tumour-driving, PI3K/AKT/mTOR pathway activating mutant PI3KαH1047R [2]. Selectivity for the mutated PI3Kα is proposed to reduce the risk of side-effects arising from on-target inhibition of wild type PI3Kα (such as hyperglycemia, rash, and diarrhea). OKI-219 is orally bioavailable and can cross the blood-brain barrier.
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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 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 2
Rotatable bonds 7
Topological polar surface area 76.12
Molecular weight 502.53
XLogP 3.95
No. Lipinski's rules broken 1

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 CC1=CC2=C(C=C(N(C)C2=O)N3CCN(CC3)CC(F)(F)F)C(=C1)[C@@H](C)NC4=C(C=CC=C4)C(=O)O
Isomeric SMILES CN1C(C2=CC(=CC(=C2C=C1N3CCN(CC3)CC(F)(F)F)[C@@H](C)NC4=C(C(=O)O)C=CC=C4)C)=O
InChI InChI=1S/C26H29F3N4O3/c1-16-12-19(17(2)30-22-7-5-4-6-18(22)25(35)36)20-14-23(31(3)24(34)21(20)13-16)33-10-8-32(9-11-33)15-26(27,28)29/h4-7,12-14,17,30H,8-11,15H2,1-3H3,(H,35,36)/t17-/m1/s1
InChI Key SGPSVGQQTKICOA-QGZVFWFLSA-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/)
References
1. Blake JF, Boys ML, MareskaDA, Payette JN, Schulte CA, Yestrepsky B, Zhao Q. (2024)
Isoquinolones as pi3k inhibitors.
Patent number: WO2024054469A1. Assignee: OnKure Inc. Priority date: 06/09/2023. Publication date: 14/03/2024.
2. Taylor M, Hoh M, Zhao D, Mareska DA, Boys ML, Izrayelit Y, Woessner R, Walker D, Winkler JD, Agresta S. (2025)
Abstract P4-12-20: OKI-219 enhances activity of SOC therapies in double and triple combinations in pre-clinical PI3Kα H1047R mutant breast cancer models.
Clin Cancer Res, 31 (12_Supplement): P4-12-20. DOI: 10.1158/1557-3265.SABCS24-P4-12-20