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Tucatinib (Irbinitinib,ARRY-380)

  Cat. No.:  DC8771   Featured
Chemical Structure
937263-43-9
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More than 5000 active chemicals with high quality for research!
Field of application
Irbinitinib(ARRY-380; ONT-380) is a potent and selective HER2 inhibitor with IC50 of 8 nM, equipotent against truncated p95-HER2, 500-fold more selective for HER2 versus EGFR.
Cas No.: 937263-43-9
Chemical Name: ARRY-380;Irbinitinib [INN]; SCHEMBL1193050; ONT-380;
Synonyms: ARRY-380;Irbinitinib [INN]; SCHEMBL1193050; ONT-380;
SMILES: N1=C2C(C=C(NC3=NC(C)(C)CO3)C=C2)=C(NC2=CC=C(OC3C=CN4N=CN=C4C=3)C(C)=C2)N=C1
Formula: C26H24N8O2
M.Wt: 480.52
Sotrage: 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Description: Tucatinib (Irbinitinib; ARRY-380; ONT-380) is a potent and selective HER2 inhibitor with an IC50 of 8 nM.
In Vivo: In preclinical studies with intracranial tumor models, treatment of mice with Tucatinib (ONT-380) compared with lapatinib or neratinib shows a survival benefit when each drug is dosed at the maximum-tolerated dose[1]. In the Tucatinib (ARRY-380)-treated-group, 75% of the animals are alive on Day 43. ARRY-380 and its active metabolite causes a significant reduction in brain pErbB2 (80%)[2]. Tucatinib (ARRY-380) demonstrates significant dose-related tumor growth inhibition (TGI; 50% at 50 mg/kg/d and 96% at 100 mg/kg/d) with numerous partial regressions (>50% reduction from baseline size) at the higher dose level in 9/12 animals. Tucatinib (50 mg/kg/d) in combination with trastuzumab shows a 98% TGI with complete regressions in 9/12 animals and two partial regressions. At dose of 100 mg/kg/d of Tucatinib in combination with trastuzumab, there is 100% TGI and all animals have complete responses[3].
In Vitro: Tucatinib (ONT-380) is a potent, selective, ATP-competitive, orally administered small-molecule inhibitor of HER2. Tucatinib has nanomolar activity against purified HER2 enzyme and is approximately 500-fold selective for HER2 versus EGFR in cell-based assays. Tucatinib selectively inhibits the receptor tyrosine kinase HER2 relative to EGFR. In HER2 overexpressing cell lines, Tucatinib blocks proliferation and the phosphorylation of HER2 and its downstream effector, Akt. By contrast, in the EGFR overexpressing cell lines, it weakly inhibits phosphorylation and proliferation, demonstrating that Tucatinib may have potential to block HER2 signaling without causing the toxicities of EGFR inhibition[1].
MSDS
COA
LOT NO. DOWNLOAD
2018-0101
2018-0101
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