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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H17F3N4O3
Molecular Weight 478.4227
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LIFIRAFENIB

SMILES

[H][C@]12OC3=CC=C(OC4=CC=NC5=C4CCC(=O)N5)C=C3[C@@]1([H])[C@@H]2C6=NC7=C(N6)C=C(C=C7)C(F)(F)F

InChI

InChIKey=NGFFVZQXSRKHBM-FKBYEOEOSA-N
InChI=1S/C25H17F3N4O3/c26-25(27,28)11-1-4-15-16(9-11)31-24(30-15)21-20-14-10-12(2-5-17(14)35-22(20)21)34-18-7-8-29-23-13(18)3-6-19(33)32-23/h1-2,4-5,7-10,20-22H,3,6H2,(H,30,31)(H,29,32,33)/t20-,21-,22-/m0/s1

HIDE SMILES / InChI

Molecular Formula C25H17F3N4O3
Molecular Weight 478.4227
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Lifirafenib (BGB-283 or BEIGENE-283), a dual inhibitor targeting BRAF kinase and EGFR, was studied for the treatment of different cancer types harboring mutations in BRAF, KRAS, and NRAS. Lifirafenib participates in Phase II clinical trial in combination with PD-0325901 to treat the patients with solid tumor.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
32.0 nM [IC50]
5.6 nM [IC50]
29.0 nM [IC50]
PubMed

PubMed

TitleDatePubMed
A high-performance liquid chromatography-tandem mass spectrometry method for the determination of lifrafenib, a novel RAF kinase and EGFR inhibitor, in human plasma and urine and its application in clinical pharmacokinetic study.
2019 Mar 20

Sample Use Guides

BGB-283 (lifirafenib) 5 or mg once a day
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:57:20 GMT 2023
Edited
by admin
on Sat Dec 16 11:57:20 GMT 2023
Record UNII
8762XZS5ZF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LIFIRAFENIB
USAN   INN  
Official Name English
5-(((1R,1AS,6BR)-1-(6-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-2-YL)-1A,6B-DIHYDRO-1H-CYCLOPROPA(B)BENZOFURAN-5-YL)OXY)-3,4-DIHYDRO-1H-1,8-NAPHTHYRIDIN-2-ONE
Systematic Name English
BGB-283
Code English
LIFIRAFENIB [USAN]
Common Name English
BEIGENE-283
Common Name English
lifirafenib [INN]
Common Name English
1,8-NAPHTHYRIDIN-2(1H)-ONE, 5-(((1R,1AS,6BR)-1A,6B-DIHYDRO-1-(6-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOL-2-YL)-1H-CYCLOPROPA(B)BENZOFURAN-5-YL)OXY)-3,4-DIHYDRO-
Systematic Name English
Lifirafenib [WHO-DD]
Common Name English
Code System Code Type Description
NCI_THESAURUS
C124995
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
PUBCHEM
89670174
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
DRUG BANK
DB14773
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
FDA UNII
8762XZS5ZF
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
INN
10554
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
USAN
FG-149
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
CAS
1446090-79-4
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
SMS_ID
300000034330
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
BEIGENE-283
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY MedKoo CAT NO.: 206465, CAS NO.: 1446090-77-2Description: BGB-283 is a Novel potent and selective RAF Kinase and EGFR inhibitor. BGB-283-displays Potent Antitumor Activity in B-RAF Mutated Colorectal Cancers. In vitro, BGB-283 potently inhibits B-RAFV600E-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harbouring B-RAFV600E and EGFR mutation/amplification. In B-RAFV600E CRC cell lines, BGB-283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell-line derived and primary human colorectal tumor xenografts bearing B-RAFV600E mutation. BGB-283 as a potent antitumor drug candidate with clinical potential for treating CRC harbouring B-RAFV600E mutation. (last updated: 5/17/2016).
ChEMBL
CHEMBL3545246
Created by admin on Sat Dec 16 11:57:20 GMT 2023 , Edited by admin on Sat Dec 16 11:57:20 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Here, we report characterization of a dual RAF kinase/EGFR inhibitor, BGB-283, which is currently under clinical investigation. In vitro, BGB-283 potently inhibits BRAF(V600E)-activated ERK phosphorylation and cell proliferation. It demonstrates selective cytotoxicity and preferentially inhibits proliferation of cancer cells harboring BRAF(V600E) and EGFR mutation/amplification. In BRAF(V600E) colorectal cancer cell lines, BGB-283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth inhibition accompanied by partial and complete tumor regressions in both cell line-derived and primary human colorectal tumor xenografts bearing BRAF(V600E) mutation. These findings support BGB-283 as a potent antitumor drug candidate with clinical potential for treating colorectal cancer harboring BRAF(V600E) mutation.