SKI-178

SKU: orb1218980

Description

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.

Key Properties

• CAS Number: 1259484-97-3
• MW: 394.43
• Purity: >98% (HPLC)
• Formula: C₂₁H₂₂N₄O₄
• SMILES: O=C(C1=CC(C2=CC=C(OC)C=C2)=NN1)N/N=C(C3=CC=C(OC)C(OC)=C3)\C
• Target: Apoptosis
• Solubility: DMSO:50 mg/mL (126.77 mM; Need ultrasonic)

Bioactivity

• In Vivo:
  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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• In Vitro:
  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.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

Apoptosis