Altiratinib

Altiratinib, also known as DCC-270, DP-5164, is an oral, selective and highly potent inhibitor of MET, TIE2, VEGFR2 and TRK kinases with potential anticancer activity. DCC-2701 effectively reduces tumor burden in vivo and blocks c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro. Importantly, DCC-2701's anti-proliferative activity was dependent on c-MET activation induced by stromal human fibroblasts and to a lesser extent exogenous HGF.

Product information

CAS Number: 1345847-93-9

Molecular Weight: 510.46

Formula: C26H21F3N4O4

Synonym:

DCC-2701

DP-5164

DCC2701

DCC 2701

DP 5164

DP5164

DP-5164.

Chemical Name: N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

Smiles: O=C(NC1C=CC(F)=CC=1)C1(CC1)C(=O)NC1=CC(F)=C(C=C1F)OC1=CC(NC(=O)C2CC2)=NC=C1

InChiKey: GNNDEPIMDAZHRQ-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Altiratinib also inhibits MET isoforms METD1228H, MET D1228N, METY1230C, METY1230D, METY1230H, METM1250T with IC50s of 3.6, 1.3, 1.2, 0.37, 1.5 and 6 nM, respectively. Altiratinib inhibits MET phosphorylation with IC50 values of 0.85 and 2.2 nM, respectively. In the U-87 glioblastoma cell line, MET and HGF are both expressed. Altiratinib blocks autocrine activation of MET phosphorylation in these cells (IC50=6.2 nM). Altiratinib potently inhibits cellular proliferation in MET-amplified EBC-1 and MKN-45 cells, as well as TPM3-TRKA fusion KM-12 cells. Activation of MET is known to increase the motility and invasiveness of cancer cells: Altiratinib inhibits HGF-induced A549 cell migration, with an IC50 of 13 nM. Altiratinib also inhibits FLT3-ITD mutant MV-4-11 cell proliferation with an IC50 of 12 nM.

In Vivo:

A single oral dose of 30 mg/kg Altiratinib leads to >95% inhibition of MET phosphorylation for the entire 24-hour period. A single 10 mg/kg oral dose of Altiratinib exhibits complete inhibition of MET phosphorylation through 12 hours and 73% inhibition at 24 hours postdose. Altiratinib dosed at 10 mg/kg twice a day leads to a significant 90% decrease in BLI signal. 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.

References:

1. Kwon Y, Smith BD, Zhou Y, Kaufman MD, Godwin AK. Effective inhibition of c-MET-mediated signaling, growth and migration of ovarian cancer cells is influenced by the ovarian tissue microenvironment. Oncogene. 2015 Jan 8;34(2):144-53. doi: 10.1038/onc.2013.539. Epub 2013 Dec 23. PubMed PMID: 24362531; PubMed Central PMCID: PMC4067476.

Products are for research use only. Not for human use.