ALTIRATINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C26H21F3N4O4
Molecular Weight	510.4645
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(NC(=O)C2(CC2)C(=O)NC3=C(F)C=C(OC4=CC=NC(NC(=O)C5CC5)=C4)C(F)=C3)C=C1

InChI

InChIKey=GNNDEPIMDAZHRQ-UHFFFAOYSA-N

InChI=1S/C26H21F3N4O4/c27-15-3-5-16(6-4-15)31-24(35)26(8-9-26)25(36)32-20-12-19(29)21(13-18(20)28)37-17-7-10-30-22(11-17)33-23(34)14-1-2-14/h3-7,10-14H,1-2,8-9H2,(H,31,35)(H,32,36)(H,30,33,34)

HIDE SMILES / InChI

Molecular Formula	C26H21F3N4O4
Molecular Weight	510.4645
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24362531 | https://www.ncbi.nlm.nih.gov/pubmed/26285778

Altiratinib, a novel c-MET/TIE-2/VEGFR inhibitor, was able to effectively reduce tumor burden in vivo and block c-MET signaling, cell growth and migration. Altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment. Altiratinib durably inhibits MET, both wild-type and mutated forms, in vitro and in vivo. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases. It is currently in Phase 1 clinical development for the treatment of solid tumors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Hepatocyte growth factor receptor 54 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	2.7 nM [IC50]
Nerve growth factor receptor Trk-A 15 Target ID: CHEMBL2815 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	0.85 nM [IC50]
NT-3 growth factor receptor 9 Target ID: CHEMBL5608 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	0.83 nM [IC50]
Neurotrophic tyrosine kinase receptor type 2 14 Target ID: CHEMBL4898 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	4.6 nM [IC50]
Tyrosine-protein kinase TIE-2 6 Target ID: CHEMBL4128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	8.0 nM [IC50]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	9.2 nM [IC50]
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778	Inhibitor 8297	9.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: http://adisinsight.springer.com/trials/700244323	Primary		Phase I 428	Unknown Approved Use Unknown
Glioblastoma 65 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26965451	Primary		Preclinical	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=377020438	yes [IC50 4.6109 uM]

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009CXG	https://www.1pchem.com/search?query=1P009CXG
AChemBlock	H-8975	http://www.achemblock.com/catalogsearch/result/?q=H-8975
AOBIOUS INC	AOB87118	http://aobious.com/aobious/search?search_query=AOB87118
Angene	AGN-PC-0WCY2Q	http://www.angenechemical.com/productshow/AGN-PC-0WCY2Q.html
ApexBio Technology	B5832	https://www.apexbt.com/catalogsearch/result/?q=B5832
AstaTech	F11464	http://astatechinc.com/CPSResult.php?CRNO=F11464
BLD Pharm	BD329094	http://www.bldpharm.com/search/Search.html?keyword=BD329094
Chem Scene	CS-3944	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3944
ChemShuttle	135043	https://www.chemshuttle.com/catalogsearch/result/?q=135043
Combi-Blocks	QM-5007	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-5007
Excenen	EX-A902	http://www.excenen.com/searchresultlist.php?id=EX-A902
MedChem Express	HY-B0791	https://www.medchemexpress.com/search.html?q=HY-B0791&ft=&fa=&fp=
MolPort	MolPort-039-333-792	https://www.molport.com/shop/molecule-link/MolPort-039-333-792
Molnova	M11387	https://www.molnova.com/en/serch-list.html?keywords=M11387
MuseChem	I001320	https://www.musechem.com/product/I001320.html
Ryan Scientific	AZ20	https://ryansci.com/products?q=AZ20&list_q=&search_type=exact
Selleck Chemicals	S6412	http://www.selleckchem.com/search.html?searchDTO.searchParam=S6412
ShangHai Biochempartner	BCP001813	http://www.biochempartner.com/search_BCP001813
ShangHai Biochempartner	BCP15682	http://www.biochempartner.com/search_BCP15682
TargetMol	T2054	https://www.targetmol.com/search?keyword=T2054
eMolecules	53744829	https://orderbb.emolecules.com/search/#?query=53744829
mcule	MCULE-7096820110	https://mcule.com/MCULE-7096820110/

PubMed

Title	Date	PubMed
Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2.	2015 Sep	26285778

Patents

Sample Use Guides

In Vivo Use Guide

In escalating dose (starting dose 15 mg) twice daily every 12 hours for a 28-day cycle

Route of Administration: Oral

In Vitro Use Guide

EBC-1 (NSCLC) and MKN-45 (gastric cancer) human cancer cell lines genomically amplify and overexpress MET with subsequent ligand-independent MET activation. Altiratinib inhibited MET phosphorylation with IC50 values of 0.85 nmol/L and 2.2 nM/L, respectively. In the U-87 glioblastoma cell line, MET and HGF are both expressed. Altiratinib blocked autocrine activation of MET phosphorylation in these cells (IC50 of 6.2 nM/L).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 10:00:26 UTC 2023` Edited by `admin` on `Sat Dec 16 10:00:26 UTC 2023`
Record UNII	T678746713
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALTIRATINIB

Official Name

English

DP-5164

Code

English

ALTIRATINIB [USAN]

Common Name

English

1,1-CYCLOPROPANEDICARBOXAMIDE, N-(4-((2-((CYCLOPROPYLCARBONYL)AMINO)-4-PYRIDINYL)OXY)-2,5-DIFLUOROPHENYL)-N'-(4-FLUOROPHENYL)-

Systematic Name

English

N-(4-((2-((CYCLOPROPYLCARBONYL)AMINO)PYRIDIN-4-YL)OXY)-2,5-DIFLUOROPHENYI)-N-(4- FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE

Systematic Name

English

Altiratinib [WHO-DD]

Common Name

English

DCC-2701

Code

English

altiratinib [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

441714