plixorafenib   Click here for help

GtoPdb Ligand ID: 9131

Synonyms: PLX 8394 | PLX-8394 | PLX8394
Compound class: Synthetic organic
Comment: PLX8394 is an investigational orally available, next-generation small molecule RAF inhibitor [2]. It has potential antineoplastic activity. Structurally, PLX8394 is similar to the first-generation BRAF inhibitor vemurafenib. PLX8394 inhibits wild-type and mutated forms of BRAF. PLX8394 and compounds like it have been termed 'paradox breakers' as they are designed to inhibit mutant BRAF kinase activity without activating the MAPK pathway in cells bearing upstream activation, as many of the original BRAF inhibitors are prone to do. PLX8394 is one of the compounds claimed in patent WO2014194127 [1]. This chemical structure is identical to that of the INN plixorafenib.
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 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.

✖
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 129.32
Molecular weight 542.13
XLogP 3.5
No. Lipinski's rules broken 0
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.

✖
Canonical SMILES FC1CCN(C1)S(=O)(=O)Nc1ccc(c(c1F)C(=O)c1c[nH]c2c1cc(cn2)c1cnc(nc1)C1CC1)F
Isomeric SMILES F[C@@H]1CCN(C1)S(=O)(=O)Nc1ccc(c(c1F)C(=O)c1c[nH]c2c1cc(cn2)c1cnc(nc1)C1CC1)F
InChI InChI=1S/C25H21F3N6O3S/c26-16-5-6-34(12-16)38(36,37)33-20-4-3-19(27)21(22(20)28)23(35)18-11-32-25-17(18)7-14(8-31-25)15-9-29-24(30-10-15)13-1-2-13/h3-4,7-11,13,16,33H,1-2,5-6,12H2,(H,31,32)/t16-/m1/s1
InChI Key YYACLQUDUDXAPA-MRXNPFEDSA-N
References
1. Zhang C, Hirth K=P, Ibrahim PN, Nespi M, Shi S, Speval W, Habets GG, burton B. (2014)
Compounds for kinase modulation, and indications therefor.
Patent number: WO2014194127 A1. Assignee: Plexxikon Inc.. Priority date: 30/05/2013. Publication date: 04/12/2014.
2. Zhang C, Spevak W, Zhang Y, Burton EA, Ma Y, Habets G, Zhang J, Lin J, Ewing T, Matusow B et al.. (2015)
RAF inhibitors that evade paradoxical MAPK pathway activation.
Nature, 526 (7574): 583-6. [PMID:26466569]