L-glycero-b-L-manno-Heptopyranosylamine,4-deoxy-4-[[2-[[(2E,4E)-1-oxo-2,4-tetradecadien-1-yl]amino]acetyl]amino]-N-1H-purin-6-yl-

KRN5500 (NSC 650426), a Spicamycin (HY-127130) derivative and a nucleoside-like antibiotic with anti-tumor activity. KRN5500 also induces apoptosis via the down-regulation of Bcl-2 expression. KRN5500 shows a significant efficacy in the human tumor xenograft model in mice[1][2].

Signaling Pathways >> Apoptosis >> Bcl-2 Family

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Infection

Bcl-2

KRN5500 (10-160 ng/mL; 0-5 d) 有效抑制 NB4、NKM-1 和 HL-60 细胞的增殖和活力[1]。 KRN5500 (40 ng/mL, 160 ng/mL; 48 h) 诱导 NB4、HL-60 和 NKM-1 细胞凋亡[1]。 KRN5500 (40 ng /mL, 80 ng /mL; 36 h) 下调 NB4 细胞中 Bcl-2 的表达[1]。 Cell Viability Assay[1] Cell Line: NB4, HL-60, NKM-1, NOP-1 and Daudi cells Concentration: 10 ng/mL, 20 ng/mL, 40 ng/mL, 80 ng/mL, 160 ng/mL Incubation Time: 0, 1, 2, 3, 4, and 5 days or 72 h Result: Completely inhibited cell proliferation and viability of NB4 and NKM-1 at about 80 ng/mL, of HL-60 at 160 ng/mL. Inhibited cells viability of IC50s of 51.6 ng/mL, 89.7 ng/mL, 66.5 ng/mL, 277.0 ng/mL, 242.1 ng/mL, respectively. Western Blot Analysis[1] Cell Line: NB4 cells Concentration: 40 ng/mL, 80 ng/mL Incubation Time: 36 h Result: Reduced the Bcl-2 expression without affecting Bcl-xL and Bax expression.

KRN5500 (4 mg/kg; 腹腔注射; 每天 1 次，共 5 天) 显示抗肿瘤活性，导致一些小鼠肿瘤和人肿瘤异种抑制模型中的肿瘤重量下降[2]。 Animal Model: Mouse model with murine tumors and human tumor xenografts[2] Dosage: 4 mg/kg Administration: Intraperitoneal injection; once daily for 5 days Result: Prolonged the survival of P388 leukemia- and B16 melanoma-bearing mice but lacked marginally effective on colon adenocarcinoma. Decreased tumor weight in 10 human stomach, 14 colon and 2 esophageal cancers.

[1]. Zhang WJ, et al. Spicamycin and KRN5500 induce apoptosis in myeloid and lymphoid cell lines with down-regulation of bcl-2 expression and modulation of promyelocytic leukemia protein. Jpn J Cancer Res. 2000 Jun;91(6):604-11.  

[2]. Kamishohara M, et al. Antitumor activity of a spicamycin derivative, KRN5500, and its active metabolite in tumor cells. Oncol Res. 1994;6(8):383-90.