Tucatinib
Tucatinib Basic information
- Product Name:
- Tucatinib
- Synonyms:
-
- ONT-380)
- N4-(4-([1
- 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]-
- 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
- Irbinitinib
- Irbinitinib(ARRY380)
- Irbinitinib (ARRY-380,Tucatinib,ONT 380)
- IRBINITINIB (ARRY-380; ONT-380)
- CAS:
- 937263-43-9
- MF:
- C26H24N8O2
- MW:
- 480.52
- EINECS:
- 200-001-8
- Product Categories:
-
- Inhibitors
- API
- Mol File:
- 937263-43-9.mol
Tucatinib Chemical Properties
- 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)
- InChI
- InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)
- 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
Tucatinib Usage And Synthesis
Description
Tucatinib is also known as ARRY-380 or Irbinitinib. 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.
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
Tucatinib, a highly selective HER2 inhibitor, was approved in 2020 as a combination therapy with trastuzumab and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.
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.
References
[1] PATRICE A LEE. In VivoActivity of ARRY-380, a Potent, Small Molecule Inhibitor of ErbB2 in Combination with Trastuzumab, Docetaxel or Bevacizumab.[J]. Cancer research, 2009, 69 1: 5104-5104. DOI:10.1158/0008-5472.SABCS-09-5104.
[2] S. MOULDER. Abstract A143: ARRY-380, a selective HER2 inhibitor: From drug design to clinical evaluation.[J]. Molecular Cancer Therapeutics, 2011, 10 1. DOI:10.1158/1535-7163.TARG-11-A143.
[3] V. DINKEL. Abstract 852: ARRY-380, a potent, small molecule inhibitor of ErbB2, increases survival in intracranial ErbB2+ xenograft models in mice[J]. Cancer research, 2012, 72 1: 852-852. DOI:10.1158/1538-7445.AM2012-852.
[4] KOCIE?SKI P. Synthesis of Tucatinib[J]. Synfacts, 2019, 24 1: 0965. DOI:10.1055/s-0039-1690496.
[5] RASHMI K MURTHY. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer.[J]. New England Journal of Medicine, 2020, 382 7: 597-609. DOI:10.1056/NEJMoa1914609.
[6] RASHMI MURTHY. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study.[J]. Lancet Oncology, 2018: 880-888. DOI:10.1016/S1470-2045(18)30256-0.
TucatinibSupplier
- Tel
- +21-18501659228 18501659228
- info@hope-chem.com
- Tel
- 05565209906 15391842992
- 794263564@qq.com
- Tel
- 15269175648
- qingyan7590@163.com
- Tel
- 0371-65741762
- sales@hasunny.com
- Tel
- 18964309092 18964309092
- 2769493375@qq.com