[CAS NO. 940929-33-9] SB-743921hydrochloride
PRODUCTS SPECIFICATIONS [940929-33-9]
DESCRIPTION [940929-33-9]
Overview
| MDL | MFCD18385010 |
|---|---|
| Molecular Weight | 553.52 |
| Molecular Formula | C31H34Cl2N2O3 |
| SMILES | ClC1=CC2=C(C(C(CC3=CC=CC=C3)=C([C@@H](C(C)C)N(C(C4=CC=C(C=C4)C)=O)CCCN)O2)=O)C=C1.Cl |
1 Publications Citing Use of MCE
Summary
SB-743921 hydrochloride is a potent inhibitor of the mitotic kinesin KSP (Eg5) , with a K i of 0.1 nM.
IC50 & Target
|
Eg5 0.1 nM (Ki) |
In Vitro
SB-743921 is a potent inhibitor of Eg5, with a K i of 0.1 nM [1] . 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 [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
SB-743921 has good oral bioavailability and pharmacokinetics and induces complete tumor regression in nude mice bearing lung cancer patient xenografts [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00343564 | Cytokinetics |
Non-Hodgkin´s Lymphoma|Hodgkin´s Disease
|
April 2006 | Phase 1|Phase 2 |
| NCT00136513 | GlaxoSmithKline |
Solid Tumor Cancer
|
April 2004 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 180.66 mM )
H 2 O : 10 mg/mL ( 18.07 mM ; ultrasonic and warming and heat to 60°C)
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.8066 mL | 9.0331 mL | 18.0662 mL |
| 5 mM | 0.3613 mL | 1.8066 mL | 3.6132 mL |
| 10 mM | 0.1807 mL | 0.9033 mL | 1.8066 mL |
References
- [1] Jeffrey R. Jackson, et al. A second generation KSP inhibitor, SB-743921, is a highly potent and active therapeutic in preclinical models of cancer. First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006.
- [2] Yin Y, et al. Kinesin spindle protein inhibitor SB743921 induces mitotic arrest and apoptosis and overcomes imatinib resistance of chronic myeloid leukemia cells. Leuk Lymphoma. 2015 Jun;56(6):1813-20.
- [3] Good JA, et al. Optimized S-trityl-L-cysteine-based inhibitors of kinesin spindle protein with potent in vivo antitumor activity in lung cancer xenograft models. J Med Chem. 2013 Mar 14;56(5):1878-93.