| Identification | Back Directory | [Name]
Irbinitinib | [CAS]
937263-43-9 | [Synonyms]
ONT-380)
6-diaMine
N4-(4-([1
Irbinitinib
4-diMethyl-4
(R)-N6-(4-Methyl-4
Irbinitinib(ARRY380)
5-dihydrooxazol-2-yl)quinazoline-4
5-a]pyridin-7-yloxy)-3-Methylphenyl)-N6-(4
5-dihydrooxazol-2-yl)-N4-(3-Methyl-4-(thiazol-2-ylMethoxy)phenyl)quinazoline-4
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine
4,6-QuinazolinediaMine, N6-(4,5-dihydro-4,4-diMethyl-2-oxazolyl)-N4-[3-Methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]- | [EINECS(EC#)]
200-001-8 | [Molecular Formula]
C26H24N8O2 | [MDL Number]
MFCD22380467 | [MOL File]
937263-43-9.mol | [Molecular Weight]
480.521 |
| Chemical Properties | Back Directory | [density ]
1.41±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF:1.0(Max Conc. mg/mL);2.08(Max Conc. mM)
DMSO:49.0(Max Conc. mg/mL);101.97(Max Conc. mM)
DMSO:PBS (pH 7.2) (1:2):0.33(Max Conc. mg/mL);0.69(Max Conc. mM) | [form ]
A crystalline solid | [pka]
6.61±0.70(Predicted) | [color ]
White to yellow | [InChIKey]
SDEAXTCZPQIFQM-UHFFFAOYSA-N | [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 |
| Questions and Answers (Q&A) | Back Directory | [Description]
Irbinitinib is also known as ARRY-380 or Tucatinib. ARRY-380 is an orally inhibitor of human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. It selectively binds to and inhibits the phosphorylation of ErbB-2, which may prevent the activation of ErbB-2 signal transduction pathways, resulting in growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cellular proliferation and differentiation. Therefore, ARRY-380 may be an alternative treatmentmethod for the treatment of HER2+ cancers.
| [References]
Lee, P., et al. "In Vivo Activity of ARRY-380, a Potent, Small Molecule Inhibitor of ErbB2 in Combination with Trastuzumab, Docetaxel or Bevacizumab." Cancer Research 69.24 Supplement(2009):5104-5104.
Moulder, S. L., et al. "Abstract A143: ARRY-380, a selective HER2 inhibitor: From drug design to clinical evaluation." Molecular Cancer Therapeutics 10.Supplement 1(2011):A143-A143.
Dinkel, Victoria, et al. "Abstract 852: ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2+ xenograft models in mice." Cancer Research 72.8 Supplement(2012).
|
| Hazard Information | Back Directory | [Characteristics]
Year of discovery: 2006
Year of introduction: 2020
Discovered by: Array BioPharma
Developed by: Array BioPharma
Primary targets: HER2
Binding type: I/II
Class: receptor tyrosine kinase
Treatment: HER2-positive breast cancer
Other names: ONT-380, ARRY-380
Oral bioavailability = not reported
Elimination half-life = 5.4 hours
Protein binding = 97% | [Uses]
N6-(4,5-Dihydro-4,4-dimethyl-2-oxazolyl)-N4-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-4,6-quinazolinediamine is a novel?diarylamine ErbB inhibitor. | [Brand name]
TukysaTM
| [Side effects]
Tukysa (tucatinib) is a brand-name prescription medication. The Active ingredient is tucatinib. Serious side effects can include diarrhoea, liver damage, and allergic reactions. Mild side effects can occur with Tukysa use. This list doesn’t include all possible mild side effects of the drug. Mild side effects that have been reported with Tukysa include nausea and vomiting, fatigue, reduced appetite, weight loss, joint pain; peripheral neuropathy (nerve damage that causes tingling, numbness, or weakness in your arms, hands, legs, or feet); abdominal pain; headache; skin rash; nosebleeds; anemia (low level of red blood cells); stomatitis; hand-foot syndrome.
| [storage]
Store at -20°C | [Mode of action]
Tucatinib binds to tyrosine kinase (an enzyme) of HER2, reducing PI3-kinase and MAP-kinase signaling. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone. |
|
|