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Purity: ≥98%
SB743921 HCl (SB-743921; SB 743921), the hydrochloride salt of SB743921, is a novel and potent inhibitor of the mitotic motor protein, kinesin spindle protein (KSP), with potential antitumor activity. It inhibits KSP with a Ki of 0.1 nM, and shows no/little activity against closely related proteins including MKLP1, Kif15, KHC, Kin2, Kif1A, Kif4 and CENP-E. SB-743921 may be used for the treatment of non-Hodgkin's lymphoma (NHL). SB-743921 acts by selectively inhibiting KSP which is an important motor protein involved in the early stages of mitosis in proliferating cells, leading to the inhibition of mitotic spindle assembly and interrupts cell division, thereby resulting in cell cycle arrest and cancer cell apoptosis.
| ln Vitro |
SB-743921 has a Ki of 0.1 nM, making it a strong inhibitor of Eg5[1]. The colony-forming capacity of primary cells from chronic myeloid leukemia (CML) is potently inhibited by SB-743921 (1 nM), although normal bone marrow progenitors show only mild inhibitory effects. While having minimal effects on normal CD34 + cells, SB-743921 (1, 3 nM) causes the apoptosis of CML primary CD34 + cells. In KCL22 and CML CD34 + cells, SB-743921 (2 nM) plus imatinib exhibits an additive anti-proliferative effect. Moreover, SB-743921 cures CML cells of their imatinib resistance. In CML cells, MEK/ERK and AKT signaling are inhibited by SB-743921 (0.5 nM, 1 nM, and 3 nM)[2].
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| ln Vivo |
In nude mice with lung cancer patient xenografts, SB-743921 causes total tumor shrinkage and has good oral bioavailability and pharmacokinetics[3].
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| 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 |
| Molecular Formula |
C31H33N2O3.HCL
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| Molecular Weight |
553.52
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| CAS # |
940929-33-9
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| Related CAS # |
SB-743921 free base;618430-39-0
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| SMILES |
ClC1C([H])=C([H])C2=C(C=1[H])OC(=C(C2=O)C([H])([H])C1C([H])=C([H])C([H])=C([H])C=1[H])[C@@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N(C(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])=O)C([H])([H])C([H])([H])C([H])([H])N([H])[H].Cl[H]
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Saline pH5.0: 30 mg/mL |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
(A) The Eg5–4allosteric binding site, illustrating interactions with proximal (4 Å) protein residues.Hydrogen bonds are represented as dashed lines. (B) The Eg5–4inhibitor-binding pocket with a solid surface illustrating the nomenclature for subpockets P1, P2, and P3. (C) Stereoplot of (R)-46in the allosteric binding site. Hydrogen bonds between inhibitor (blue) and Eg5 residues (beige) are depicted by black broken lines. Coordinate and structure factor files for the Eg5–46complex (PDB ID: 4BBG) were deposited at the PDB.J Med Chem.2013 Mar 14;56(5):1878-93. |
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Antitumor efficacy ofrac-11,34,36, andrac-42compared to the clinical candidate1in a subcutaneous tumor xenograft model with LXFS 538.J Med Chem.2013 Mar 14;56(5):1878-93. |
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