Plixorafenib

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H21F3N6O3S
Molecular Weight	542.533
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

F[C@@H]1CCN(C1)S(=O)(=O)NC2=CC=C(F)C(C(=O)C3=CNC4=NC=C(C=C34)C5=CN=C(N=C5)C6CC6)=C2F

InChI

InChIKey=YYACLQUDUDXAPA-MRXNPFEDSA-N

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

HIDE SMILES / InChI

Molecular Formula	C25H21F3N6O3S
Molecular Weight	542.533
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26466569
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02428712

PLX8394 is a potent and selective inhibitor of B-Raf V600E (IC50 14 nM for WT and 3.8 nM for V600E mutant). Unlike vermurafenib, sorafenib and dabrafenib, PLX8394 does not cause paradoxical MAPK pathway activation. PLX8394 is under investigation in phase I/II of clinical trial for the treatment patients with advanced unresectable solid tumors.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase B-raf 21 Target ID: P15056\|\|\|Q13878 Gene ID: 673.0 Gene Symbol: BRAF Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26466569	Inhibitor 8504
Serine/threonine-protein kinase RAF 11 Target ID: CHEMBL1906 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26466569	Inhibitor 8504		23.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: https://clinicaltrials.gov/ct2/show/NCT02428712	Primary		Phase II 1147	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
900 mg 2 times / day multiple, oral RP2D Dose: 900 mg, 2 times / day Route: oral Route: multiple Dose: 900 mg, 2 times / day Sources: https://mct.aacrjournals.org/content/17/1_Supplement/B176	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://mct.aacrjournals.org/content/17/1_Supplement/B176	DLT: Transaminitis... Dose limiting toxicities: Transaminitis (grade 3, 16.7%) Sources: https://mct.aacrjournals.org/content/17/1_Supplement/B176

AEs

AE	Significance	Dose	Population
Transaminitis	grade 3, 16.7% DLT	900 mg 2 times / day multiple, oral RP2D Dose: 900 mg, 2 times / day Route: oral Route: multiple Dose: 900 mg, 2 times / day Sources: https://mct.aacrjournals.org/content/17/1_Supplement/B176	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://mct.aacrjournals.org/content/17/1_Supplement/B176

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363681140	no
CYP3A4 1946	substrate 4014 Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2583	yes		yes (co-administration study) Comment: Cobicistat increased systemic exposure by 2-3-fold Sources: https://ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.2583

PubMed

Title	Date	PubMed
RAF inhibitors that evade paradoxical MAPK pathway activation.	2015-10-22	26466569

Patents

Sample Use Guides

In Vivo Use Guide

In phase 1/2 clinical trials against advanced unresectable solid tumors PLX8394 75 mg tablets are administered orally.

Route of Administration: Oral

In Vitro Use Guide

PLX7904 inhibited the in vitro growth of two melanoma cell lines (A375 and COLO829) and an additional human colorectal cancer cell line COLO205 that expressed BRAFV600E with IC50 values of 0.17 mM, 0.53 mM, and 0.16 mM. Cell growth was measured using CellTiter assay; cells were incubated with the compound for 72 h.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:33:49 GMT 2025` Edited by `admin` on `Mon Mar 31 22:33:49 GMT 2025`
Record UNII	J2L7Z273SG
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FORE-8394

Preferred Name

English

Plixorafenib

Official Name

English

plixorafenib [INN]

Common Name

English

PLX8394

Code

English

1-PYRROLIDINESULFONAMIDE, N-(3-((5-(2-CYCLOPROPYL-5-PYRIMIDINYL)-1H-PYRROLO(2,3-B)PYRIDIN-3-YL)CARBONYL)-2,4-DIFLUOROPHENYL)-3-FLUORO-, (3R)-

Systematic Name

English

FORE8394

Code

English

PLX-8394

Code

English

PLX 8394 [WHO-DD]

Common Name

English

Code System Code Type Description

NCI_THESAURUS

C113330