U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C26H25N3O4
Molecular Weight 443.4944
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LUCITANIB

SMILES

CNC(=O)C1=C2C=CC(OC3=CC=NC4=CC(OCC5(N)CC5)=C(OC)C=C34)=CC2=CC=C1

InChI

InChIKey=CUDVHEFYRIWYQD-UHFFFAOYSA-N
InChI=1S/C26H25N3O4/c1-28-25(30)19-5-3-4-16-12-17(6-7-18(16)19)33-22-8-11-29-21-14-24(23(31-2)13-20(21)22)32-15-26(27)9-10-26/h3-8,11-14H,9-10,15,27H2,1-2H3,(H,28,30)

HIDE SMILES / InChI

Molecular Formula C26H25N3O4
Molecular Weight 443.4944
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Lucitanib (E-3810) is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. A Phase I/IIa clinical trial of lucitanib was initiated in 2010 and has demonstrated multiple objective responses in FGFR1 gene-amplified breast cancer patients, and objective responses were also observed in patients with tumors often sensitive to VEGFR inhibitors, such as renal cell and thyroid cancer. Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 through 3 (FGFR1-3), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFR alpha-beta). The most common adverse events were hypertension, asthenia, and proteinuria.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
7.0 nM [IC50]
12.0 nM [IC50]
4.0 nM [IC50]
13.0 nM [IC50]
8.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

PubMed

Sample Use Guides

In Vivo Use Guide
Once daily (q.d.), on a continuous schedule over 28-day cycles, in fasting conditions (at least 2 hours prior to and 2 hours after any meal), until progressive disease or unacceptable toxicity. Starting dose is 10 mg/day and can be reduced in 2.5 mg decrements to 5 mg/day based on individual tolerability.
Route of Administration: Oral
In Vitro Use Guide
the recovery of VEGFR2 phosphorylation after AL3810 washout was examined in HUVEC cells. Treatment with 1 uM/L of AL3810 for 4 hrs caused a dramatic decrease in the level of phospho-VEGFR2. Upon the removal of the inhibitor, VEGFR2 phosphorylation was recovered substantially at 6 hrs, followed by a total restoration at 24 hrs after inhibitor washout, indicating that AL3810 is a reversible inhibitor.
Substance Class Chemical
Record UNII
PP449XA4BH
Record Status Validated (UNII)
Record Version