Sepantronium Bromide **
產品名稱：Sepantronium Bromide
產品貨號：LC S-7272
產品規格：100 MG
Sepantronium bromide, also known as YM155, is a novel small molecule inhibitor of expression of the survivin protein, which itself is an inhibitor of apoptosis.
Sepantronium bromide inhibited the the growth of various human cancer cell lines in vitro with GI50 values of 8.2 nM for null p53 PC-3, 2.3 nM for mutant p53 PPC-1, 4.0 nM for mutant p53 DU145, 8.2 nM for mutant p53 TSU-Prl, 11 nM for mutant p53 22Rvl hormone refractory prostate cancer cells; 4.2 nM for wt p53 SK-MEL-5, and 6.3 nM for wt p53 A375 malignant melanoma. Sepantronium bromide also induced extensive regression of xenografted PC-3 tumors in mice. Nakahara, T., et al. "YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts." Cancer Res. 67: 8014-8021 (2007).
Sepantronium bromide sensitized human non-small cell lung cancer (NSCLC) cells to γ-radiation both in vitro and in vivo. Iwasa, T., et al. "Radiosensitizing effect of YM155, a novel small-molecule survivin suppressant, in non-small cell lung cancer cell lines." Clin. Cancer Res. 14: 6496-6504 (2008).
The uptake of [14C]sepantronium bromide into PC-3, lung cancer (Calu-6 and NCI-H358), malignant melanoma (A375 and SK-MEL-5), and non-Hodgkin's lymphoma (RL and Ramos) cell lines was dependent on incubation time, temperature, and drug concentration. Sepantronium bromide was taken up into these different cancer cells in a carrier-mediated manner and with a similar affinity (Km = 0.189-0.367 µM). Minematsu, T., et al. "Carrier-mediated uptake of 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium bromide (YM155 monobromide), a novel small-molecule survivin suppressant, into human solid tumor and lymphoma cells." Drug Metab. Dispos. 37: 619-628 (2009).
Sepantronium bromide blocked the growth of 119 human cancer cell lines, with the greatest inhibition in lines derived from non-Hodgkin's lymphoma, hormone-refractory prostate cancer, ovarian cancer, sarcoma, non-small-cell lung cancer, breast cancer, leukemia and melanoma with an average GI50 of 15 nM. Sepantronium bromide inhibited the growth of tumor cell lines regardless of their p53 status and demonstrated significant antitumor activity in 5 various mice xenograft models without showing significant bodyweight loss. It also caused tumor regressions in vivo, possibly by its effects in reducing intratumoral survivin expression levels, increasing apoptosis and decreasing mitotic indices. Nakahara, T., et al. "Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models." Cancer Sci. 102: 614-621 (2011).
Sepantronium bromide demonstrated modest single-agent activity in patients with refractory and advanced non-small-cell lung cancer (NSCLC) in a multicenter phase II trial. A favorable safety/tolerability profile for sepantronium bromide was reported. Giaccone, G., et al. "Multicenter phase II trial of YM155, a small-molecule suppressor of survivin, in patients with advanced, refractory, non-small-cell lung cancer." J. Clin. Oncol. 27: 4481-4486 (2009).
Sepantronium bromide induced autophagy-dependent apoptosis in prostate cancer cells. Wang, Q., et al. "Induction of autophagy-dependent apoptosis by the survivin suppressant YM155 in prostate cancer cells." Cancer Lett. 302: 29-36 (2011).
Sepantronium bromide induced spontaneous apoptosis of melanoma cells, possibly by inhibiting survivin. It also demonstrated antiproliferative effects at nanomolar levels and caused tumor regression in established melanoma xenograft models. Yamanaka, K., et al. "Antitumor Activity of YM155, a Selective Small-Molecule Survivin Suppressant, Alone and in Combination with Docetaxel in Human Malignant Melanoma Models." Clin. Cancer Res. 17: 5423-5431 (2011).
Sepantronium bromide induced decreased cellular proliferation and spontaneous apoptosis of human metastatic triple negative breast cancer cells (TNBC, with negative expression of estrogen and progesterone receptors and no overexpression of HER2/neu (ErbB-2)). In a preclinical TNBC mouse xenograft model, continuous treatment with sepantronium bromide caused the complete regression of subcutaneously established tumors. This compound inhibited spontaneous metastases and significantly improved the survival of animals bearing established metastatic tumors. Yamanaka, K., et al. "YM155, a selective survivin suppressant, inhibits tumor spread and prolongs survival in a spontaneous metastatic model of human triple negative breast cancer." Int. J. Oncol. 39: 569-575 (2011).
A phase II clinical trial showed that sepantronium bromide had modest activity in taxane-pretreated castration-resistant prostate cancer (CRPC) and was also well tolerated. Tolcher, A.W., et al. "A phase II study of YM155, a novel small-molecule suppressor of survivin, in castration-resistant taxane-pretreated prostate cancer." Ann. Oncol. Aug 22 (2011) [Epub ahead of print].
Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A
