tinlorafenib   Click here for help

GtoPdb Ligand ID: 12096

Synonyms: ARRY-461 | ARRY461 | PF-07284890 | PF07284890
PDB Ligand
Compound class: Synthetic organic
Comment: We obtained the chemical structure for tinlorafenib from the WHO's proposed INN list 127 (21 July 2022). In this document it was described as an antineoplastic. The INN indicates that it is a RAF kinase inhibitor. Further investigations revealed that tinlorafenib has the synonyms PF-07284890 and ARRY-461, that it inhibits BRAF and CRAF, and that it is orally bioavailable and able to cross the blood-brain barrier [1]. Formal name>structure and mechanism of action was disclosed in Ren et al. (2024) [2].
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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 5
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 101.47
Molecular weight 456.08
XLogP 4.21
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 FCCCS(=O)(=O)Nc1ccc(c(c1Cl)Nc1ccc2c(c1C)c(=O)n(cn2)C)F
Isomeric SMILES Clc1c(ccc(c1Nc1c(c2c(=O)n(cnc2cc1)C)C)F)NS(=O)(=O)CCCF
InChI InChI=1S/C19H19ClF2N4O3S/c1-11-13(6-7-14-16(11)19(27)26(2)10-23-14)24-18-12(22)4-5-15(17(18)20)25-30(28,29)9-3-8-21/h4-7,10,24-25H,3,8-9H2,1-2H3
InChI Key VVLVISDSGRHLMB-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. Bouhana K, Anderson D, DeWolf W, Brown S, Williams L, Ren L, Moreno D, Wallace R, Fell JB, Hartley D et al.. (2021)
Abstract 1473: Nonclinical development of PF-07284890 (ARRY-461), a potent, brain-penetrant, small molecule inhibitor of BRAF V600-mutation-driven tumors in vitro and in vivo.
Cancer Research, 81: 1473. DOI: 10.1158/1538-7445.AM2021-1473
2. Ren L, Moreno D, Baer BR, Barbour P, Bettendorf T, Bouhana K, Brown K, Brown SA, Fell JB, Hartley DP et al.. (2024)
Identification of the Clinical Candidate PF-07284890 (ARRY-461), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer.
J Med Chem, 67 (15): 13019-13032. [PMID:39077892]