SKI-178

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

SKI-178 是一种鞘氨醇激酶 1 (SphK1) 抑制剂，IC50 为 0.1-1.8 μM。

SKI-178 is a sphingosine kinase 1 (SphK1) inhibitor with IC50 of 0.1-1.8 μM.?It induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade.?The sustained activation of CDK1 during prolonged mitosis, mediated by SKI-178 leads to the simultaneous phosphorylation of the prosurvival Bcl-2 family members, Bcl-2 and Bcl-xl, as well as the phosphorylation and subsequent degradation of Mcl-1.?

Apoptosis Analysis Cell Line:HL-60 cells Concentration:5 μM Incubation Time:24 hours Result:JNK activity (indicated by phosphorylation at Thr183/Tyr185) increased in a time-dependent manner starting as early as 2 hours continued to increase for at least 24 hours. There was a concomitant increase in apoptotic cell death indicated by the cleavage of caspase-7. Bcl-2 phosphorylation at Ser70 increased with time in response to SKI-178 treatment, reaching maximal levels at 8 hours, which was consistent with the timing of caspase-7 activation.

Animal Model:MLL-AF9 mouse model (leukemic mice)Dosage:20 mg/kg Administration:Retro-orbital injection under isoflurane anesthesia; three times per week for 1 and 3 weeks Result:White blood cell (WBC) counts decreased from their initial 104 cells/μL levels and continued to decline after 3 weeks of treatment until they reached normal levels (~4×103 cells/μL).

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Apoptosis

Apoptosis

Apoptosis|SphK1|SphK2

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1259484-97-3

394.43

C21H22N4O4

>98% (HPLC)

DMSO:50 mg/mL?(126.77 mM;?Need ultrasonic)

O=C(C1=CC(C2=CC=C(OC)C=C2)=NN1)N/N=C(C3=CC=C(OC)C(OC)=C3)\C

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(-20℃)

With Ice Pack

≥ 2 years