TAK-285 

TAK-285 is a potent, selective, ATP-competitive and orally active HER2 and EGFR(HER1) inhibitor with IC₅₀ of 17 nM and 23 nM, respectively. TAK-285 is >10-fold selectivity for HER1/2 than HER4, and less potent to MEK1/5, c-Met, Aurora B, Lck, CSK etc. TAK-285 has effective antitumor activity^[1]. TAK-285 can cross the blood-brain barrier (BBB)^[2].

TAK-285 (Compound 34e) shows significant growth inhibitory activity against BT-474 cells (HER2-overexpressing human breast cancer cell line) with GI₅₀ of 17 nM^[1]. TAK-285 (Compound 34e) exhibits HER4 inhibitory activity with an IC₅₀ value of 260 nM. TAK-285 also inhibits MEK1, MEK5, c-Met, Aurora B, Lck, CSK and Lyn B with IC₅₀s of 1100 nM, 5700 nM, 4200 nM, 1700 nM, 2400 nM, 4700 nM and 5200 nM, respectively^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

TAK-285 (Compound 34e; 50-100 mg/kg; oral administration; twice daily; for 14 days; female BALB/cAJcl mice) treatment exhibits dose-dependent tumor growth inhibition (tumor/control ratio [T/C]): 44% and 11% at 50 and 100 mg/kg, respectively) without significant body weight loss in mice^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

547.96

Solid

C₂₆H₂₅ClF₃N₅O₃

871026-44-7

ClC(C=C(NC1=NC=NC2=C1N(CCNC(CC(C)(C)O)=O)C=C2)C=C3)=C3OC4=CC=CC(C(F)(F)F)=C4

Room temperature in continental US; may vary elsewhere.

• [1]. Ishikawa T, et al. 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. J Med Chem. 2011 Dec 8;54(23):8030-50.  [Content Brief]

  [2]. Erdo F, et al. Verification of brain penetration of the unbound fraction of a novel HER2/EGFR dual kinase inhibitor (TAK-285) by microdialysis in rats. Brain Res Bull. 2012 Mar 10;87(4-5):413-9.  [Content Brief]