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Purity: =98.73%
SNS-032 (also known as BMS-387032; SNS 032; BMS387032; SNS032), a 2-aminothiazole based small-molecule, is a potent and selective inhibitor of CDK2 (cyclin dependent kinase 2) with potential antitumor activity. In cell-free experiments, it inhibits CDK2 with an IC50 of 48 nM and exhibits 10- and 20-fold selectivity over CDK1/CDK4. SNS-032 binds specifically to CDKs 2, 7, and 9, inhibiting their phosphorylation and activation. In tumor cell populations that are susceptible, this inhibition of CDK activity may lead to cell cycle arrest, apoptosis induction, and decreased tumor cell proliferation. There is evidence that this agent can make radioresistant tumor cells more susceptible to ionizing radiation.
| Targets |
CDK9 (IC50 = 4 nM); CDK2 (IC50 = 38 nM); CDK7 (IC50 = 62 nM); CDK1 (IC50 = 480 nM); CDK4 (IC50 = 925 nM)
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| ln Vitro |
SNS-032 exhibits low sensitivity to CDK1, with an IC50 of 480 nM, and CDK4 at 925 nM. In vitro, SNS-032 efficiently eradicates cells with chronic lymphocytic leukemia, irrespective of treatment history and prognostic markers. SNS-032 is more effective than flavopiridol and roscovitine in both RNA synthesis inhibition and apoptosis induction. The activity of SNS-032 is easily reversible; SNS-032 removal reactivates RNA polymerase II, which results in Mcl-1 resynthesis and cell survival[1]. SNS-032 prevents endothelial cells from forming three-dimensional capillary networks. SNS-032 totally stops HUVECs from forming capillaries through U87MG cell-mediated mechanisms. Furthermore, SNS-032 significantly inhibits both cell lines' ability to produce VEGF, which is linked to its ability to inhibit in vitro angiogenesis. Preclinical research has demonstrated that SNS-032 causes apoptosis and cell cycle arrest in a variety of cell lines[2]. SNS-032 inhibits CDKs 2 and 7 to stop the cell cycle, and CDKs 7 and 9 to inhibit transcription. Human serum has no effect on SNS-032 activity[3]. SNS-032 causes caspase-3 activation and annexin V staining to increase in a dose-dependent manner. SNS-032 inhibits the expression of CDK2 and CDK9 and dephosphorylates CDK7, while at the molecular level it causes a marked dephosphorylation of RNA polymerase (RNA Pol) II's serine 2 and 5[5].
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| ln Vivo |
SNS-032 (15 mg/kg, i.p.) inhibits KBM5-T315I cells as well as xenografted BaF3-T674I cells in vivo. When T674I PDGFRα and T315I-Bcr-Abl are downregulated in tumors transplanted into nude mice, SNS-032 stops the tumors from growing[4].
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| Enzyme Assay |
SNS-032 exhibits selectivity against CDK2, CDK7, and CDK9, as evidenced by its IC50 values of 38 nM, 62 nM, and 4 nM, respectively.
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| Cell Assay |
The growth curves of both HUVECs and U87MG cells are measured using the Cell Titer-Glo (CTG) luminescent assay. A total of 100 milliliters is used to seed U87MG cells and HUVECs (2×103 cells/well) in a 96-well microplate. Cells are exposed to different concentrations of SNS-032 (0-0.5 mM) for 24, 48, or 72 hours following the 24-hour mark. Following the treatment's completion, 100 mL of CTG solution is added to each well, and the wells are then left in the dark and at room temperature for 20 minutes. The lysate (50 mL) is put into a 96-well white plate, and POLARstar OPTIMA is used to measure luminescence. When calculating percentage cell growth, 100% growth at the time of SNS-032 addition is taken into account.
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| Animal Protocol |
Simple nu/nu In barrier facilities with a 12-hour light-dark cycle, BALB/c mice are kept with unlimited access to food and water. On the flanks of 4- to 6-week-old male nude mice, a mixture of 1×107 BaF3-T674I cells with Matrigel or KBM5-T315I cells (3×107) is subcutaneously injected. Calipers are used every other day to measure tumors. The formula for calculating tumor volumes is a2×b×0.4, where a is the diameter that is the smallest and b is the diameter that is perpendicular to a. After the subcutaneous inoculation, mice are randomized to receive treatment with either vehicle (tissue culture medium containing 0.1% v/v) or SNS-032 (15 mg/kg injected intraperitoneally every two days) for approximately two weeks, or until the tumors are palpable (approximately 100 mm3). Prior to dilution, SNS-032 is dissolved in tissue culture grade DMSO. Each animal's body weight, eating habits, and level of motor activity are tracked as measures of overall health. Tumor xenografts are then promptly removed, weighed, stored, and fixed after the animals are put to sleep.
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| References |
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| Molecular Formula |
C17H24N4O2S2
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|---|---|
| Molecular Weight |
380.53
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| Exact Mass |
380.13
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| Elemental Analysis |
C, 53.66; H, 6.36; N, 14.72; O, 8.41; S, 16.85
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| CAS # |
345627-80-7
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| Related CAS # |
345627-80-7;345627-90-9 (HCl);
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| Appearance |
white solid powder
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| SMILES |
CC(C)(C)C1=CN=C(O1)CSC2=CN=C(S2)NC(=O)C3CCNCC3
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| InChi Key |
OUSFTKFNBAZUKL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H24N4O2S2/c1-17(2,3)12-8-19-13(23-12)10-24-14-9-20-16(25-14)21-15(22)11-4-6-18-7-5-11/h8-9,11,18H,4-7,10H2,1-3H3,(H,20,21,22)
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| Chemical Name |
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide
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| Synonyms |
BMS-387032; SNS 032; BMS387032; SNS032; BMS 387032; SNS-032
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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: ≥ 2.08 mg/mL (5.47 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 20.8 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: ≥ 2.08 mg/mL (5.47 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 20.8 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: ≥ 2.08 mg/mL (5.47 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: 30% PEG400+0.5% Tween80+5% Propylene glycol : 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6279 mL | 13.1396 mL | 26.2791 mL | |
| 5 mM | 0.5256 mL | 2.6279 mL | 5.2558 mL | |
| 10 mM | 0.2628 mL | 1.3140 mL | 2.6279 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00446342 | Completed | Drug: SNS-032 Injection | Multiple Myeloma Mantle Cell Lymphoma |
Sunesis Pharmaceuticals | February 2007 | Phase 1 |
| NCT00292864 | Completed | Drug: SNS-032 Injection | Tumors | Sunesis Pharmaceuticals | January 2006 | Phase 1 |
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