TAK-285

SKU: orb1301128

Description

TAK-285

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 871026-44-7
• MW: 547.96
• Purity: 99.73%
• Formula: C₂₆H₂₅ClF₃N₅O₃
• SMILES: CC(C)(O)CC(=O)NCCn1ccc2ncnc(Nc3ccc(Oc4cccc(c4)C(F)(F)F)c(Cl)c3)c12
• Target: MEK,HER,Aurora Kinase,EGFR
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:50 mg/mL (91.25 mM);DMSO:102 mg/mL (186.14 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (7.3 mM)

Bioactivity

• Target IC50:
  EGFR/HER1:23 nM|HER2:17 nM
• In Vivo:
  The oral bioavailability of TAK-285 is 97.7% in rats and 72.2% in mice at a dose of 50 mg/kg. Oral administration of TAK-285 at 100 mg/kg twice daily for 14 days displays significant antitumor efficacy in the HER2-overexpressing BT-474 tumor xenograft mouse model with tumor/control (T/C) ratio of 29%, without affecting body weight. Similar to the BT-474 model, TAK-285 exhibits dose-dependent tumor growth inhibition of 4-1ST (HER2-overexpressing human gastric cancer tumor) xenografts in mice, with T/C of 44% and 11% at doses of 50 mg/kg and 100 mg/kg, twice daily, respectively, without significant body weight loss in mice. Furthermore, TAK-285 treatment induces dose-dependent growth inhibition of 4-1ST tumors in rats with T/C of 38% and 14% at doses of 6.25 mg/kg and 12.5 mg/kg, and, particularly noteworthy, tumor regression with T/C of -12% and -16% at doses of 25 mg/kg and 50 mg/kg, respectively. After oral administration of TAK-285, a significant amount of TAK-285 is present in the brain of rats in pharmacologically active, unbound form (approximately 20% of its free plasma level), indicating that TAK-285 has a potential in the therapy of CNS malignancies/metastases.
• In Vitro:
  Among the 34 kinases tested, TAK-285 only significantly inhibits HER4 with IC50 of 260 nM, slightly inhibits MEK1, MEK5, c-Met, Aurora B, Lck, CSK, and Lyn B with IC50 of 1.1 μM, 5.7 μM, 4.2 μM, 1.7 μM, 2.4 μM, 4.7 μM, and 5.2 μM, respectively, and displays no activity against other kinases with IC50 of >10 μM. TAK-285 shows significant growth inhibitory activity against BT-474 cells (HER2-overexpressing human breast cancer cell line) with GI50 of 17 nM. Compared with SYR127063 a potent inhibitor of HER2, TAK-285 displays similar in vitro potency against HER2 and EGFR. Compared with the full cytoplasmic domains of the wild-type proteins, the mutations and shortened boundaries used for structure determination of HER2-KD and EGFR-KD do not significantly change the inhibitory activity (IC50) of TAK-285. TAK-285 binds to the inactive conformation of EGFR, and shows a similar binding mode with lapatinib in the active site.
• Cell Research:
  The cells are treated continuously with various concentrations of TAK-285 for 5 days. The live cell numbers are counted with a particle analyzer.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, orally, Epidermal growth factor receptor, EGFR/HER1, EGFR, ErbB-1, MEK1, HER1, HER2, HER4, Inhibitor, CNS, antitumor, Aurora B, Aurora Kinase, AuroraKinase, penetration, TAK 285, TAK285, TAK-285

Compound Identifiers

PubChem CID

11620908