Supinoxin

Research use only, not for human use.

Supinoxin is an orally active inhibitor of phosphorylated-p68 RNA helicase and a potent first-in-class anti-cancer agent.

Supinoxin is an orally active inhibitor of phosphorylated-p68 RNA helicase and a potent first-in-class anti-cancer agent. Supinoxin induces cell apoptosis and inhibits the growth of TNBC cancer cell lines (IC50s:10 nM - 20 nM).(In Vitro):Supinoxin inhibits cell growth, MDA-MB-231, Caki-1, UMRC2, PANC-1, A549, MKN-45, HepG2, HCT116, HT29, PC-3, U251, HeLa, SK-MEL-28 and OVCAR-3 (IC50: range from 0.01 μM to 0.021 μM in the growth inhibition of cancer cells). Supinoxin (0-10 μM; 72 hours) is active against cell lines of all TNBC molecular subtypes and is active against cell lines with mutations in p53, RB1, CDKN2A, and loss of PTEN. Supinoxin (20-100 nM; 24 hours) treatment causes a dose-dependent increase in tetraploid cells, consistent with induction of G2–M cell-cycle arrest. Supinoxin (0-100 nM; 24 or 48 hours) reduces MCL-1 expression in a dose-dependent manner in TNBC cell lines sensitive to Supinoxin. Supinoxin (0-100 nM; 72 hours) exhibits no significant induction of apoptosis in cell lines resistant to the antiproliferative effects of Supinoxin. But in sensitive cells, the observed activation of apoptosis begins at 24–48 hours and reaches a peak at 72 hours. The induced apoptosis is treated with a dose of 100 nM .(In Vivo):Supinoxin (p.o.; 160/320/600 mg/kg; once weekly for 3 weeks) obviously dose-dependent tumor growth inhibition in the MDA-MB-231 model, exhibits TGI of 55.7%, 80.29% and 94.58% at 160 mg/kg, 320 mg/kg and 600 mg/kg, respectively .

Cell Viability Assay Cell Line:MDA-MB-231, HCC1806, Hs578t, CAL-85-1, HCC38, HCC1187, MDA-MB-436, CAL-51, HCC38, BT549, MDAMB-157, HDQ-P1, HCC1395, MDA-MB-436, HCC1937, CAL-120, BT20 cellsConcentration:0-10 μM Incubation Time:72 hours Result:Displayed the average IC50 of the cell lines sensitive to RX-5902 treatment is 56 nM.Cell Cycle AnalysisCell Line:Sensitive (MDA-MB-231 and HCT1806) and two resistant (MDA-MB-436 and CAL-120) cell lines Concentration:20 nM; 100 nM Incubation Time:24 hours Result:Led to G2-M cell-cycle arrest at sensitive cells.Apoptosis Analysis Cell Line:Sensitive (MDA-MB-231 and HCT1806) and two resistant (MDA-MB-436 and CAL-120) cell lines Concentration:0-100 nMIncubation Time:24-72 hours Result:Induced cell apoptosis in sensitive cell lines and peaks at 72 hours.Western Blot Analysis Cell Line:Cal-51, HCC-1806, and MDA-MB-468 cells Concentration:20 nM; 100 nM Incubation Time:24 hours Result:Induced inhibition of MCL-1expression in Cal-51, HCC-1806, and MDA-MB-468 cells.

Animal Model:MDAMD-231 xenograft model in miceDosage:160 mg/kg; 320 mg/kg; 600 mg/kg Administration:Oral administration; once weekly for 3 weeks Result:Decreased tumor volume as a dose-dependent manner.

RX-5902

Apoptosis

Apoptosis

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888478-45-3

441.463

C22H24FN5O4

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (226.52 mM)

COc1cc(OC)cc(c1)N1CCN(CC1)C(=O)Nc1nc2cc(F)ccc2nc1OC

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(-20℃)

With Ice Pack

≥ 2 years