ocifisertib   Click here for help

GtoPdb Ligand ID: 12083

Synonyms: CFI-400945 | CFI400945
Compound class: Synthetic organic
Comment: We obtained the chemical structure for ocifisertib from the WHO's proposed INN list 127 (21 July 2022). In this document it was described as a serine/ threonine kinase inhibitor and antineoplastic. The SMILES converted from the IUPAC in the INN list maps to PubChem CID 58486178, which has the Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 as one of its synonyms. CFI-400945 is first-in-class oral, and selective inhibitor of polo-like kinase 4 (PLK4) [1-2]. It has advanced to clinical evaluation in selected cancer patients.
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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 5
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 79.48
Molecular weight 534.26
XLogP 5.19
No. Lipinski's rules broken 1
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 COc1ccc2c(c1)[C@]1(C[C@H]1c1ccc3c(c1)[nH]nc3/C=C/c1ccc(cc1)CN1C[C@H](C)O[C@@H](C1)C)C(=O)N2
Isomeric SMILES C[C@@H]1CN(C[C@@H](O1)C)Cc1ccc(cc1)/C=C/c1n[nH]c2cc(ccc12)[C@@H]1C[C@]21C(=O)Nc1ccc(cc21)OC
InChI InChI=1S/C33H34N4O3/c1-20-17-37(18-21(2)40-20)19-23-6-4-22(5-7-23)8-12-29-26-11-9-24(14-31(26)36-35-29)28-16-33(28)27-15-25(39-3)10-13-30(27)34-32(33)38/h4-15,20-21,28H,16-19H2,1-3H3,(H,34,38)(H,35,36)/b12-8+/t20-,21+,28-,33-/m0/s1
InChI Key DADASRPKWOGKCU-FVTQAUBDSA-N
No information available.
Summary of Clinical Use Click here for help
CFI-400945 has progressed to clinical evaluation in patients with advanced solid tumours and haematological cancers. The FDA granted orphan designation in Jan. 2024 for the treatment of acute myeloid leukemia (AML).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
PLK4 regulates centriole duplication and so is essential for cell division and proliferation. Inhibition of PLK4 has anti-proliferative action.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04176848 CFI-400945 and Durvalumab in Patients With Advanced Triple Negative Breast Cancer Phase 2 Interventional Canadian Cancer Trials Group
NCT03624543 CFI-400945 in Patients With Advanced/Metastatic Breast Cancer Phase 2 Interventional Canadian Cancer Trials Group
NCT03187288 Study of CFI-400945 Fumarate in Patients With Relapsed or Refractory AML or MDS Phase 1 Interventional University Health Network, Toronto
NCT03385655 Prostate Cancer Biomarker Enrichment and Treatment Selection Phase 2 Interventional Canadian Cancer Trials Group
NCT01954316 A Study of CFI-400945 Fumarate in Patients With Advanced Cancer Phase 1 Interventional University Health Network, Toronto CFI-400945 (64 mg) was well tolerated in patients with advanced solid tumours. Dose-limiting toxicities (e.g. neutropenia) were observed above 64 mg. 3