Tucatinib
FDA Approval- Product Name
- Tucatinib
- CAS No.
- 937263-43-9
- Chemical Name
- Tucatinib
- Synonyms
- Tucatinib;N4-(4-([1,2,4]triazolo[1,5-α]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine;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]-;CS-1710;ONT-380);6-diaMine;N4-(4-([1;Tacatinib;Tocatinib;Ttucatinib
- CBNumber
- CB32616075
- Molecular Formula
- C26H24N8O2
- Formula Weight
- 480.52
- MOL File
- 937263-43-9.mol
Tucatinib Property
- 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
- 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
Hazard and Precautionary Statements (GHS)
- Symbol(GHS)
-
- Signal word
- Warning
- Hazard statements
-
H315Causes skin irritation
H319Causes serious eye irritation
H335May cause respiratory irritation
- Precautionary statements
-
P261Avoid breathing dust/fume/gas/mist/vapours/spray.
P280Wear protective gloves/protective clothing/eye protection/face protection.
P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
P405Store locked up.
N-Bromosuccinimide Price
- Product number
- D449790
- Product name
- ARRY-380
- Packaging
- 25mg
- Price
- $1760
- Updated
- 2021/12/16
- Product number
- CS-3906
- Product name
- Tucatinib
- Purity
- 99.82%
- Packaging
- 100mg
- Price
- $450
- Updated
- 2021/12/16
- Product number
- 8979DH
- Product name
- Tucatinib
- Packaging
- 25mg
- Price
- $590
- Updated
- 2021/12/16
- Product number
- CS-3906
- Product name
- Tucatinib
- Purity
- 99.82%
- Packaging
- 10mg
- Price
- $90
- Updated
- 2021/12/16
- Product number
- CS-3906
- Product name
- Tucatinib
- Purity
- 99.82%
- Packaging
- 50mg
- Price
- $250
- Updated
- 2021/12/16
Tucatinib Chemical Properties,Usage,Production
FDA Approval
Tucatinib was approved by USFDA in 2020.
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.
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.
Synthesis
Phenol 395 and chloropyridine 396 underwent SNAr reaction in the presence of base and elevated temperature to give diaryl ether 397. Diaryl ether 397 was treated with DMF-DMA (dimethylformamide dimethyl acetal) and hydroxylamine hydrochloride to give aryl carboxamide 398. Next, treatment with trifluoroacetic anhydride resulted in cyclization to give triazolopyridine 399. Finally, reduction of the nitro group completed the preparation of aniline 400. Aniline 401 was converted to carboxamide 402 by the action of DMF-DMA. Next, reduction of the nitro group in carboxamide 402 preserved the nitrile group in 403. Reaction with the thiocarbonyl equivalent of TCDI allowed for thiocarbonyl insertion between commercially available 404 and aniline to give thiourea 405. Aniline 400 was reacted with nitrile 405 in the presence of acid and mild heating to give aminoquinoline 406. Activation of thiourea 405 with acid and methanesulfonyl chloride in aqueous solution resulted in the formation of 2H-aminooxazine to generate tucatinib.
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.
Tucatinib Preparation Products And Raw materials
Raw materials
Preparation Products
Tucatinib Suppliers
- Tel
- 0371-65741762
- Fax
- QQ：2860768577
- sales@hasunny.com
- Country
- China
- ProdList
- 2380
- Advantage
- 58
- Tel
- Fax
- 86-21-57758967
- sales@boylechem.com
- Country
- China
- ProdList
- 2922
- Advantage
- 55
- Tel
- 18210857532; 18210857532
- Fax
- 86-10-82849933
- jkinfo@jkchemical.com
- Country
- China
- ProdList
- 96815
- Advantage
- 76
- Tel
- 0512-68780025 18962125825
- sales@ryanchem.com
- Country
- China
- ProdList
- 167
- Advantage
- 62
- Tel
- 0411-62910999 13889544652
- sales@meilune.com
- Country
- China
- ProdList
- 4747
- Advantage
- 58
- Tel
- +21-18501659228 18501659228
- Fax
- sales@hope-chem.com
- info@hope-chem.com
- Country
- China
- ProdList
- 474
- Advantage
- 55
- Tel
- 021-58170097
- info@topbiochem.com
- Country
- China
- ProdList
- 9510
- Advantage
- 58
- Tel
- 021-02136680027 15800370750
- 1706640024@qq.com
- Country
- China
- ProdList
- 570
- Advantage
- 56
- Tel
- 021-58950125
- Fax
- (86) 21-58955996
- info@chemexpress.com
- Country
- China
- ProdList
- 7552
- Advantage
- 61
- Tel
- 021-58955995
- Fax
- 609-228-5909
- sales@medchemexpress.cn
- Country
- United States
- ProdList
- 4861
- Advantage
- 58
View Lastest Price from Tucatinib manufacturers
- Product
- Tucatinib 937263-43-9
- Price
- US $0.00-0.00/kg
- Min. Order
- 1kg
- Purity
- ＞99.5% by HPLC
- Supply Ability
- 100kg/month
- Release date
- 2023-02-18
- Product
- Tucatinib 937263-43-9
- Price
- US $0.00-0.00/mg
- Min. Order
- 10mg
- Purity
- 99% HPLC
- Supply Ability
- 10000
- Release date
- 2024-09-20
- Product
- Irbinitinib 937263-43-9
- Price
- US $0.00/KG
- Min. Order
- 1KG
- Purity
- 98%
- Supply Ability
- 1000KGS
- Release date
- 2023-06-19