Ganetespib

Ganetespib (STA-9090) is a unique triazolone-containing Hsp90 inhibitor with an IC50 of 4 nM in OSA 8 cells. (In Vitro) :Ganetespib causes depletion of receptor tyrosine kinases, extinguishing of downstream signaling, inhibition of proliferation and induction of apoptosis with IC50 values ranging 2-30 nM in genomically-defined NSCLC cell lines. Ganetespib is also approximately 20-fold more potent in isogenic Ba/F3 pro-B cells rendered IL-3 independent by expression of EGFR and ERBB2 mutants. Ganetespib exhibits potent in vitro cytotoxicity in a range of solid and hematologic tumor cell lines, induces the degradation of known Hsp90 client proteins, displays superior potency to the ansamycin inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) . Ganetespib is a potent HSP90 inhibitor, and shown to kill canine tumor cell lines in vitro. Ganetespib possesses superior JAK/STAT inhibitory activity to both P6 and 17-AAG in terms of potency or duration of response in the HEL92.1.7 cells. (In Vivo) :Ganetespib (125 mg/kg, i.v.) accumulates in tumors relative to normal tissues and displays greater in vivo efficacy than 17-AAG without increased toxicity and inhibits proliferation and induces apoptosis in parallel with EGFR depletion in NCI-H1975 xenografts. Ganetespib (100, 125, 150 mg/kg, i.v.) shows potent antitumor efficacy in solid and hematologic xenograft models of oncogene addiction, as evidenced by significant growth inhibition and/or regressions.

888216-25-9

STA-9090

>98% (HPLC)

DMSO: 40 mg/mL (109.76 mM)

O=C1NN=C (C2=CC (C (C) C) =C (O) C=C2O) N1C3=CC4=C (N (C) C=C4) C=C3

C20H20N4O3

364.4

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.