871026-44-7

Basic information

• Product Name: TAK-285
• Synonyms: TAK-285;TAK-285(TAK 285);N-[2-[4-[[3-Chloro-4-[3-(trifluoromethyl)phenoxy]phenyl]amino]-5H-pyrrolo[3,2-d]pyrimidin-5-yl]ethyl]-3-hydroxy-3-methylbutanamide;N-(2-(4-(3-Chloro-4-(3-(trifluoromethyl)phenoxy)phenylamino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)e
• CAS NO: 871026-44-7
• Molecular Formula: C26H25ClF3N5O3
• Molecular Weight: 547.9566096
• EINECS: 1533716-785-6
• Product Categories: Inhibitors
• Mol File: 871026-44-7.mol
• Article Data: 2

Chemical Properties

• Melting Point: 167-169℃
• Boiling Point: 705.5±60.0 °C(Predicted)
• Appearance: /
• Density: 1.39
• Solubility: ≥27.4 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• PKA: 14.56±0.29(Predicted)
• CAS DataBase Reference: TAK-285(CAS DataBase Reference)
• NIST Chemistry Reference: TAK-285(871026-44-7)
• EPA Substance Registry System: TAK-285(871026-44-7)

Safety Data

• Hazardous Substances Data: 871026-44-7(Hazardous Substances Data)

Usage

Uses

TAK-285 is a novel dual HER2 and EGFR inhibitor with IC50 of 17 nM and 23 nM, respectively.

Biological Activity

tak-285 is a potent inhibitor of her2 and egfr with ic50 value of 17 nm and 23 nm, respectively [1].egfr (epidermal growth factor receptor) and her2 are members of erbb family of receptors and play an important role in stimulating its intrinsic intracellular protein-tyrosine kinase activity. it has been shown that the over-expressions of her-2 and egfr are correlated with a variety of cancers and thus be regarded as promising target in clinic [2].tak-285 is a selective her2 and egfr inhibitor and has a different selectivity with the reported her inhibitor ast-6. when tested with a panel of breast cancer cell lines, cells over-expressed her2 (bt-474, nci-n87, sk-br-3, calu-3, and mda-mb-453) or egfr (a-431) were more sensitive to tak-285 treatment while normal expressed cell line (mrc-5) was less sensitive [1]. [3].in rat model with 4-1st (over-express her2) or a-431 (over-express egfr) subcutaneous xenograft, administration of tak-285 caused significant reduction of tumor growth with t/c values of 14% and 13%, respectively, at a dose of 12.5 mg/kg, compared with control group [1]. in a panel of human breast cancer cell lines expressing egfr, her2, her3, and her4, administration of tak-285 significantly inhibited cell proliferation in a dose-dependent manner with ic50 values range from 0.011 to 17 μm [3].it is also reported that tak-285 inhibited akt and mapk phosphorylation with ic50 value of 0.015 μm and <0.0063 μm, respectively [1].

references

[1]. nakayama, a., et al., antitumor activity of tak-285, an investigational, non-pgp substrate her2/egfr kinase inhibitor, in cultured tumor cells, mouse and rat xenograft tumors, and in an her2-positive brain metastasis model. j cancer, 2013. 4(7): p. 557-65.[2]. lyakhov, i., et al., her2- and egfr-specific affiprobes: novel recombinant optical probes for cell imaging. chembiochem, 2010. 11(3): p. 345-50. [3]. takagi, s., et al., her2 and her3 cooperatively regulate cancer cell growth and determine sensitivity to the novel investigational egfr/her2 kinase inhibitor tak-285. oncoscience, 2014. 1(3): p. 196-204.

Upstream product

• 871026-37-8 tert-butyl [2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl]carbamate 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 98-17-9 3-Trifluoromethylphenol 
• 40718-14-7 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline 
• 40718-13-6 2-chloro-4-nitro-1-(3-(trifluoromethyl)phenoxy)benzene 
• 84905-80-6 4-Chloro-5H-pyrrolo[3,2-d]pyrimidine 
• 625-08-1 3-Hydroxy-3-methylbutyric acid 

Relevant articles and documents

Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d]pyrimidine scaffold

Dual inhibitors of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) have been investigated for breast, lung, gastric, prostate, and other cancers; one, lapatinib, is currently approved for breast cancer. To develop novel HER2/EGFR dual kinase inhibitors, we designed and synthesized pyrrolo[3,2-d]pyrimidine derivatives capable of fitting into the receptors' ATP binding site. Among the prepared compounds, 34e showed potent HER2 and EGFR (HER1) inhibitory activities as well as tumor growth inhibitory activity. The X-ray cocrystal structures of 34e with both HER2 and EGFR demonstrated that 34e interacts with the expected residues in their respective ATP pockets. Furthermore, reflecting its good oral bioavailability, 34e exhibited potent in vivo efficacy in HER2-overexpressing tumor xenograft models. On the basis of these findings, we report 34e (TAK-285) as a promising candidate for clinical development as a novel HER2/EGFR dual kinase inhibitor.