TAK-285

Research use only, not for human use.

TAK-285 is a novel dual HER2 and EGFR(HER1) inhibitor with IC50 of 17 nM and 23 nM, >10-fold selectivity for HER1/2 than HER4, less potent to MEK1/5, c-Met, Aurora B, Lck, CSK etc. Phase 1.

TAK-285 is a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2. Methods: TAK-285 is currently being developed by Takeda. TAK-285 was found to be well tolerate in Phase I trials. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300?mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300?mg b.i.d. The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.

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.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 andLyn B with IC50s of 1100 nM, 5700 nM, 4200 nM, 1700 nM, 2400 nM, 4700 nM and 5200 nM, respectively.

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. Animal Model:Female BALB/cAJcl mice (7-weeks old) with 4?1ST xenograft models Dosage:50 mg/kg, 100 mg/kg Administration:Oral administration; twice daily; for 14 days Result:Exhibited dose-dependent tumor growth inhibition.

TAK285, TAK285, TAK 285

Endocrinology/Hormones

Opioid Receptor

Aurora B| EGFR/HER1| HER2| HER4| MEK1

Cancer

——

871026-44-7

547.96

C26H25ClF3N5O3

>98% (HPLC)

DMSO : ≥ 50 mg/mL9; 1.25 mM

CC(C)(O)CC(=O)NCCN1C=CC2=C1C(NC1=CC=C(OC3=CC=CC(=C3)C(F)(F)F)C(Cl)=C1)=NC=N2

N-(2-(4-((3-chloro-4-(3-(trifluoromethyl)phenoxy)phenyl)amino)-5H-pyrrolo[3,2-d]pyrimidin-5-yl)ethyl)-3-hydroxy-3-methylbutanamide

(-20℃)

With Ice Pack

≥ 2 years