Tanespimycin

Tanespimycin (17-AAG) is a potent HSP90 inhibitor with an IC₅₀ of 5 nM, having a 100-fold higher binding affinity for tumour cell derived HSP90 than normal cell derived HSP90^[1][5]. Tanespimycin depletes cellular STK38/NDR1 and reduces STK38 kinase activity. Tanespimycin also downregulates the stk38 gene expression^[3]. IC50 & Target: IC50: 5 nM (HSP90)^[5] In Vitro: Tanespimycin causes the degradation of HER2, Akt, and both mutant and wild-type AR and the retinoblastoma-dependent G1 growth arrest of prostate cancer cells. Tanespimycin inhibits prostate cancer cell lines with IC₅₀s ranged from 25-45 nM (LNCaP, 25 nM; LAPC-4, 40 nM; DU-145, 45 nM; and PC-3, 25 nM)^[1].
Tanespimycin (0.1-1 μM) induces a nearly complete loss of ErbB2 on ErbB2-overexpressing breast cancer cells^[2]. Tanespimycin inhibits cell growth and induces G2/M cell cycle arrest and apoptosis in CCA cells together with the down-regulation of Bcl-2, Survivin and Cyclin B1, and the up-regulation of cleaved PARP^[3]. In Vivo: Tanespimycin (25-200 mg/kg, i.p.) causes a dose-dependent decline in AR, HER2, and Akt expression in prostate cancer xenografts. Tanespimycin treatment at doses sufficient to induce AR, HER2, and Akt degradation results in the dose-dependent inhibition of androgen-dependent and -independent prostate cancer xenograft growth without toxicity^[1].
Tanespimycin (60 mg/kg) with Rapamycin (30 mg/kg) inhibits A549 and MDA-MB-231 tumor growth and effects tumor cures in MDA-MB-231 tumor-bearing animals by tail vein injection^[4].