Filanesib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Filanesib 是一种选择性驱动蛋白纺锤体蛋白抑制剂 (KSP, IC50 = 6 nM)，具有有效的抗增殖活性。

Filanesib is a selective inhibitor of kinesin spindle protein (KSP, IC50 = 6 nM) with potent anti-proliferative activity.(In Vitro):Filanesib shows anti-proliferative activity in multidrug-resistant cell lines including HCT-15, NCI/ADR-RES and K562/ADR with EC50 values of 3.7, 14 and 4.2 nM respectively. Filanesib (10 nM) blocks mitosis with the monopolar spindle structure typical of KSP inhibition as judged by both increased phosphorylation of histone H3 and the accumulation of cyclin B1 in four cells . Filanesib (1 nM) induces a significant G2M cell cycle block in OCI-AML3 cells at 24 hours .(In Vivo):Filanesib (10, 15, 20, 30 mg/kg, i.p.) is active in UISO-BCA-1 xenograft, and also superior to paclitaxel in mice bearing subcutaneous HT-29, HCT-116, MDA-MB-231 and A2780 xenografts. Filanesib is superior to docetaxel in the androgen receptor-negative prostate cancer xenograft model PC-3 . RPMI 8226 tumor xenografts are particularly sensitive to low doses of Filanesib (12.5 mg/kg, i.p.) . Filanesib significantly inhibits tumor growth in HL60 and MV4-11 xenografts of SCID mice at concentrations of 27 mg/kg and 20 mg/kg, respectively .

Filanesib induces mitotic arrest in multiple cell lines.Filanesib exhibits anti-proliferative against a broad range of human and rodent tumor cell lines, including a variety of leukemias and solid tumors, with EC50s between 0.4 nM and 14.4 nM.Filanesib (0.001-0.1 nM; 36 hours) induces apoptosis in a dose-dependent manner in HeLa cells.Filanesib (3.13-6.25 nM; 44 hours) causes accumulation of cells in the G2/M phase of the cell cycle in a dose-dependent manner in HeLa cells.Filanesib potently induces cell cycle block and subsequent death in leukemic cells via the mitochondrial pathway and has potential to eradicate AML progenitor cells.Filanesib (3 μM; 6-24 hours) is able to induce caspase-2 activation.Filanesib (0.003-3 μM; 24-48 hours) is cytotoxic in Type II EOC cells. Apoptosis Analysis Cell Line:Hela cells Concentration:0.01-0.1 nM Incubation Time:36 hours Result:Induced the formation of nucleosomes and activation of caspases-3 and 7.Cell Cycle Analysis Cell Line:HeLa cells Concentration:0.78 nM, 1.56 nM, 3.13 nM, 6.25 nM Incubation Time:44 hours Result:Resulted in G2/M arrest.Western Blot Analysis Cell Line:Type II EOC cells Concentration:3 μM Incubation Time:6 hours, 12 hours, 24 hoursResult:Induced caspase-2 activation in a time-dependent manner.Cell Cytotoxicity Assay Cell Line:Type II EOC cell lines (A2780, CP70, 01-28)Concentration:0.003 μM, 0.03 μM, 0.3μM, 3 μM Incubation Time:24 hours , 48 hours Result:Effectively decreased cell viability in a time-dependent manner in the Type II EOC cell lines.

Filanesib (20 mg/kg, 30 mg/kg; i.p.; q4dx3) has anti-tumor activitiy in vivo. Animal Model:Female nude mice, EOC mice xenograft model Dosage:20 mg/kg, 30 mg/kg Administration:Intraperitoneal injection, q4dx3 Result:Induced a decrease in tumor kinetics in a dose-dependent manner.

ARRY 520 | ARRY-520

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Other Targets

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885060-09-3

420.48

C20H22F2N4O2S

>98% (HPLC)

In Vitro:?DMSO : ≥ 100 mg/mL (237.82 mM)

CN(C(=O)N1C(SC(=N1)C2=C(C=CC(=C2)F)F)(CCCN)C3=CC=CC=C3)OC

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(-20℃)

With Ice Pack

≥ 2 years