SB-743921

SKU: orb1223576

Description

SB-743921 is a potent, selective kinesin spindle protein (KSP) inhibitor with Ki of 0.1 nM, shows no activity against MKLP1, Kin2, Kif1A, Kif15, KHC, Kif4 and CENP-E; also shows high affinity for mouse KSP with Ki of 0.12 nM; blocks assembly of a functional mitotic spindle, thereby causing cell cycle arrest in mitosis and subsequent cell death in cancer cells, demonstrates improved potency over ispinesib in both biochemical and cellular assays; shows a broad spectrum of tumor inhibition in multiple cancer models.Blood Cancer Phase 2 Discontinued(In Vitro):SB-743921 is a potent inhibitor of Eg5, with a Ki of 0.1 nM. SB-743921 (1 nM) potently inhibits colony forming cell (CFC) formation of chronic myeloid leukemia (CML) primary cells, but exhibits slight inhibitory activities on the colony-forming ability of normal bone marrow progenitors. SB-743921 (1, 3 nM) induces apoptosis of CML primary CD34 + cells, and shows slight effect on normal CD34 + cells. SB-743921 (2 nM) in combination with imatinib displays additive anti-proliferative effect in KCL22 and CML CD34 + cells. Furthermore, SB-743921 overcomes imatinib resistance in CML cells. SB-743921 (0.5 nM, 1 nM, 3 nM) inhibits MEK/ERK and AKT signaling in CML cells.(In Vivo):SB-743921 has good oral bioavailability and pharmacokinetics and induces complete tumor regression in nude mice bearing lung cancer patient xenografts.

Key Properties

• CAS Number: 940929-33-9
• MW: 553.5193
• Purity: >98% (HPLC)
• Formula: C₃₁H₃₄Cl₂N₂O₃
• SMILES: CC1=CC=C(C=C1)C(=O)N(CCCN)C(C2=C(C(=O)C3=C(O2)C=C(C=C3)Cl)CC4=CC=CC=C4)C(C)C.Cl
• Target: Kinesin
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  SB-743921 has good oral bioavailability and pharmacokinetics and induces complete tumor regression in nude mice bearing lung cancer patient xenografts.
• In Vitro:
  SB-743921 is a potent inhibitor of Eg5, with a Ki of 0.1 nM. SB-743921 (1 nM) potently inhibits colony forming cell (CFC) formation of chronic myeloid leukemia (CML) primary cells, but exhibits slight inhibitory activities on the colony-forming ability of normal bone marrow progenitors. SB-743921 (1, 3 nM) induces apoptosis of CML primary CD34 + cells, and shows slight effect on normal CD34 + cells. SB-743921 (2 nM) in combination with imatinib displays additive anti-proliferative effect in KCL22 and CML CD34 + cells. Furthermore, SB-743921 overcomes imatinib resistance in CML cells. SB-743921 (0.5 nM, 1 nM, 3 nM) inhibits MEK/ERK and AKT signaling in CML cells.

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

SB743921 | SB 743921

Quick Database Links

Gene Symbol

Kinesin