LUCITANIB

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 Search

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

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://newdrugapprovals.org/2015/01/28/lucitanib-a-vegfrfgfr-dual-kinase-inhibitor-in-phase-2-triald/
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800031368 | https://www.pharmacodia.com/yaodu/html/v1/chemicals/e9507053dd36cb9217816ffb566c8720.html | https://www.ncbi.nlm.nih.gov/pubmed/25193991

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 Target	Pharmacology	Potency
Fibroblast growth factor receptor 1 45 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22304225	Inhibitor 8297	7.0 nM [IC50]
Vascular endothelial growth factor receptor 1 41 Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22304225	Inhibitor 8297	12.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22304225	Inhibitor 8297	4.0 nM [IC50]
Platelet-derived growth factor receptor alpha 30 Target ID: CHEMBL2007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22304225	Inhibitor 8297	13.0 nM [IC50]
Platelet-derived growth factor receptor beta 56 Target ID: CHEMBL1913 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22304225	Inhibitor 8297	8.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://www.pharmacodia.com/yaodu/html/v1/chemicals/e9507053dd36cb9217816ffb566c8720.html http://adisinsight.springer.com/drugs/800031368	Primary	Phase II 1132	Unknown Approved Use Unknown
Lung cancer 69 Sources: https://www.pharmacodia.com/yaodu/html/v1/chemicals/e9507053dd36cb9217816ffb566c8720.html https://clinicaltrials.gov/ct2/show/NCT02109016	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25193991	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678252	inconclusive [IC50 20.5962 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=377020414	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=377020414	yes [IC50 7.5637 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=377020414	yes [IC50 8.4866 uM]

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	3598AH	https://aksci.com/item_detail.php?cat=3598AH
ApexBio Technology	A3378	https://www.apexbt.com/catalogsearch/result/?q=A3378
Axon MedChem	1942	https://www.axonmedchem.com/product/1942
BLD Pharm	BD629871	http://www.bldpharm.com/search/Search.html?keyword=BD629871
Chem Scene	CS-0782	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0782
ChemShuttle	135143	https://www.chemshuttle.com/catalogsearch/result/?q=135143
Debye Scientific	DA-33429	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-33429
Excenen	EX-A2052	http://www.excenen.com/searchresultlist.php?id=EX-A2052
MedChem Express	HY-15391	https://www.medchemexpress.com/search.html?q=HY-15391&ft=&fa=&fp=
MolPort	MolPort-028-720-419	https://www.molport.com/shop/molecule-link/MolPort-028-720-419
MolPort	MolPort-042-665-782	https://www.molport.com/shop/molecule-link/MolPort-042-665-782
MuseChem	I000297	https://www.musechem.com/product/I000297.html
Ryan Scientific	101-93967	https://ryansci.com/products?q=101-93967&list_q=&search_type=exact
ShangHai Biochempartner	BCP000630	http://www.biochempartner.com/search_BCP000630
ShangHai Biochempartner	BCP05747	http://www.biochempartner.com/search_BCP05747
eMolecules	233175698	https://orderbb.emolecules.com/search/#?query=233175698
eMolecules	44811380	https://orderbb.emolecules.com/search/#?query=44811380
eMolecules	44818039	https://orderbb.emolecules.com/search/#?query=44818039
eMolecules	85163648	https://orderbb.emolecules.com/search/#?query=85163648
eNovation Chemicals	D501800	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501800&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-8573771094	https://mcule.com/MCULE-8573771094/
mcule	MCULE-9137744877	https://mcule.com/MCULE-9137744877/

PubMed

Title	Date	PubMed
AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and anti-tumour activity via targeting VEGFR, FGFR and PDGFR.	2012 Oct	22304225
Newly discovered angiogenesis inhibitors and their mechanisms of action.	2012 Sep	22922347

Patents

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 Created by `admin` on `Sat Dec 16 04:16:12 UTC 2023` Edited by `admin` on `Sat Dec 16 04:16:12 UTC 2023`
Record UNII	PP449XA4BH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LUCITANIB

Official Name

English

E-3810

Code

English

LUCITANIB [USAN]

Common Name

English

Lucitanib [WHO-DD]

Common Name

English

lucitanib [INN]

Common Name

English

S-80881

Code

English

1-NAPHTHALENECARBOXAMIDE, 6-((7-((1-AMINOCYCLOPROPYL)METHOXY)-6-METHOXY-4-QUINOLINYL)OXY)-N-METHYL-

Systematic Name

English

6-({7-[(1-Aminocyclopropyl)methoxy]-6-methoxyquinolin-4-yl}oxy)-N-methylnaphthalene-1-carboxamide

Systematic Name

English

S80881

Code

English

CO-3810

Code

English

AL-3810

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C93259