Ispinesib

SKU: orb1225268

Description

A potent, selective, cell-permeable, allosteric inhibitor of Eg5 (mitotic kinesin KSP) with Ki of 2.3 nM; displays >10,000-fold selectivity for Eg5 over a range of other mitotic kinesins; induces a monopolar spindle phenotype, leading to the activation of a spindle assembly checkpoint, mitotic arrest, and subsequent cell death with GI50 of 20-80 nM in colon, pancreas, prostrate, and lung cancer cells; demonstrates tumor regression of breast cancer cell xenografts in mice at 10 mg/kg.Breast Cancer Phase 2 Clinical(In Vitro):Ispinesib is a potent, highly specific inhibitor of KSP, with a Ki app of 1.7 nM. Ispinesib (150 nM) inhibits BT-474 and MDA-MB-468 cell lines, with GI50s of 45 and 19 nM, respectively. Ispinesib (SB715992, 15 and 30 nM) suppresses the proliferation of PC-3 prostate cancer cell by 48.65% and 52.16%, and induces apoptosis of prostate cancer cell by 1094.88% and 1516.70%, respectively. Ispinesib up regulates genes responsible for apoptosis and cell cycle arrest, and down regulates genes responsible for cell proliferation and survival. The anti-proliferation and pro-apoptotic activities of Ispinesib can be enhanced by genistein.(In Vivo):Ispinesib (SCID, 8 mg/kg; nude, 10 mg/kg, q4d × 3) reduces tumor volume in mice bearing tumor xenografts of ER-positive (MCF7), HER2-positive (KPL4, HCC1954, and BT-474), and triple-negative (MDA-MB-468) breast cancer cells via i.p. one dose every 4 days repeated three times.

Key Properties

• CAS Number: 336113-53-2
• MW: 517.0616
• Purity: >98% (HPLC)
• Formula: C₃₀H₃₃ClN₄O₂
• SMILES: O=C(N(CCCN)[C@@H](C(N1CC2=CC=CC=C2)=NC3=C(C=CC(Cl)=C3)C1=O)C(C)C)C4=CC=C(C)C=C4
• Target: Kinesin
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Ispinesib (SCID, 8 mg/kg; nude, 10 mg/kg, q4d × 3) reduces tumor volume in mice bearing tumor xenografts of ER-positive (MCF7), HER2-positive (KPL4, HCC1954, and BT-474), and triple-negative (MDA-MB-468) breast cancer cells via i.p. one dose every 4 days repeated three times.
• In Vitro:
  Ispinesib is a potent, highly specific inhibitor of KSP, with a Ki app of 1.7 nM. Ispinesib (150 nM) inhibits BT-474 and MDA-MB-468 cell lines, with GI50s of 45 and 19 nM, respectively. Ispinesib (SB715992, 15 and 30 nM) suppresses the proliferation of PC-3 prostate cancer cell by 48.65% and 52.16%, and induces apoptosis of prostate cancer cell by 1094.88% and 1516.70%, respectively. Ispinesib up regulates genes responsible for apoptosis and cell cycle arrest, and down regulates genes responsible for cell proliferation and survival. The anti-proliferation and pro-apoptotic activities of Ispinesib can be enhanced by genistein.

Storage & Handling

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

Alternative Names

SB-715992 | SB 715992 | SB715992

Quick Database Links

Gene Symbol

Kinesin