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.
Physicochemical Properties
| Molecular Formula | C31H33N2O3.HCL | |
| Molecular Weight | 553.52 | |
| Exact Mass | 552.194 | |
| CAS # | 940929-33-9 | |
| Related CAS # | SB-743921 free base;618430-39-0 | |
| PubChem CID | 49867937 | |
| Appearance | Off-white to yellow solid powder | |
| LogP | 8.036 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 9 | |
| Heavy Atom Count | 38 | |
| Complexity | 813 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | CC1=CC=C(C=C1)C(=O)N(CCCN)[C@@H](C2=C(C(=O)C3=C(O2)C=C(C=C3)Cl)CC4=CC=CC=C4)C(C)C.Cl |
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| InChi Key | MLMZVWABFOLFGV-LNLSOMNWSA-N | |
| InChi Code | InChI=1S/C31H33ClN2O3.ClH/c1-20(2)28(34(17-7-16-33)31(36)23-12-10-21(3)11-13-23)30-26(18-22-8-5-4-6-9-22)29(35)25-15-14-24(32)19-27(25)37-30;/h4-6,8-15,19-20,28H,7,16-18,33H2,1-3H3;1H/t28-;/m1./s1 | |
| Chemical Name | N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxochromen-2-yl)-2-methylpropyl]-4-methylbenzamide;hydrochloride | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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) |
Biological Activity
| 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]. | ||
| ln Vivo | In nude mice with lung cancer patient xenografts, SB-743921 causes total tumor shrinkage and has good oral bioavailability and pharmacokinetics[3]. | ||
| Animal Protocol |
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| References |
[1]. 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]. 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]. 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. |
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| Additional Infomation |
See also: Sb-743921 (annotation moved to). Drug Indication Investigated for use/treatment in cancer/tumors (unspecified) and lymphoma (non-hodgkin's). |
Solubility Data
| 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. 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. 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 corn oil and mix evenly. Solubility in Formulation 4: Saline pH5.0: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |