claturafenib   Click here for help

GtoPdb Ligand ID: 13808

Synonyms: ARRY-440 | ARRY440 | PF-07799933 | PF07799933
Compound class: Synthetic organic
Comment: The chemical structure for claturafenib was derived from WHO proposed INN list 132 (Feb 2025), in which it is listed as a B-Raf (BRAF) inhibitor, with antineoplastic potential. This generated a SMILES match via PubChem to a compound claimed in patent WO2021250521A1 (Array Biopharma; Pfizer acquisition) [1]. This is the INN for Pfizer's clinical candidate PF-07799933 (formerly ARRY-440) whose structure is presented in supplementary figure S2 [2]. PF-07799933 is an orthosteric, pan-mutant BRAF inhibitor that can cross the blood-brain barrier. It disrupts BRAF-containing dimers, including those containing V600 and non-V600 BRAF mutants but does not alter formation of CRAF homodimers and ARAF-containing dimers. PF-07799933 may also alter BRAF-MEK complex formation.
Click here for help

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.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 102.49
Molecular weight 490.31
XLogP 1.23
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
Click here for help

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/)

✖
Canonical SMILES CN1C=NC2=C(C(=C(C=C2)NC3=C(C(=CC=C3F)NS(=O)(=O)N4CC(C4)F)Cl)Cl)C1=O
Isomeric SMILES CN1C=NC2=C(C1=O)C(=C(C=C2)NC3=C(C=CC(=C3Cl)NS(=O)(=O)N4CC(C4)F)F)Cl
InChI InChI=1S/C18H15Cl2F2N5O3S/c1-26-8-23-11-4-5-12(15(19)14(11)18(26)28)24-17-10(22)2-3-13(16(17)20)25-31(29,30)27-6-9(21)7-27/h2-5,8-9,24-25H,6-7H2,1H3
InChI Key SHENFUUACGRLOZ-UHFFFAOYSA-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. Bettendorf TM, Doerner Barbour PM, Khan DR, Kellum AA, Laird ER, Moreno DA, Ren L. (2021)
4-oxo-3,4-dihydroquinazolinon compounds for the treatment of braf-associated diseases and disorders.
Patent number: WO2021250521A1. Assignee: Array Biopharma Inc.. Priority date: 04/06/2021. Publication date: 16/12/2021.
2. Yaeger R, McKean MA, Haq R, Beck JT, Taylor MH, Cohen JE, Bowles DW, Gadgeel SM, Mihalcioiu C, Papadopoulos KP et al.. (2024)
A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation.
Cancer Discov, 14 (9): 1599-1611. [PMID:38691346]