Size | Price | |
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5mg | ||
25mg | ||
100mg | ||
500mg |
Purity: ≥98%
Samuraciclib (CEC-0942; PPDA-001; CT-7001) is an orally bioavailable and selective CDK7 (Cyclin-dependent kinases) inhibitor with the potential for cancer treatment. It has IC50s of 41 nM and 578 nM for CDK7/CycH/MAT1 and CDK2/cycE1, respectively. Samuraciclib selectively inhibits CDK7, with an IC50 of 40nM; IC50 values for CDK1, CDK2, CDK5 and CDK9 were 45-, 15-, 230- and 30-fold higher. In vitro studies show that a wide range of cancer types are sensitive to CDK7 inhibition with GI50 values ranging between 0.2-0.3 µM.
ln Vitro |
Apoptosis is promoted by samuraciclib (ICEC0942; 0–10 µM; 24 hours; HCT116 cells) therapy [1]. Cell cycle arrest is caused by samuraciclib (ICEC0942; 0–10 µM; 24 hours; HCT116 cells) therapy [1]. In HCT116 colon cancer cells, samuraciclib (ICEC0942; 0–10 µM; 0–24 hours) treatment suppresses PolII CTD phosphorylation in a dose- and time-dependent manner. Moreover, samuraciclib prevents retinoblastoma, CDK1, and CDK2 from being phosphorylated [1]. With GI50 values of 0.18 µM, 0.32 µM, and 0, samuraciclib (ICEC0942) suppresses the development of MCF7, T47D, MDA-MB-231, HS578T, MDA-MB-468, MCF10A, and HMEC cells. In that order, 33 µM, 0.21 µM, 0.22 µM, 0.67 µM, and 1.25 µM [1].
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ln Vivo |
On day 14, therapy with samuraciclib (ICEC0942; 100 mg/kg; oral gavage; daily; for 14 days; female nu/nu-BALB/c athymic nude mice) significantly reduced tumor growth by 60%, and PolII significantly decreased the phosphorylation of Ser2 and Ser5 in tumors and PBMCs [1]. Combination therapy with ICI 47699 and Samuraciclib (ICEC0942) showed total growth arrest of tumor xenografts positive for estrogen receptors [1].
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Cell Assay |
Apoptosis analysis[1]
Cell Types: HCT116 Cell Tested Concentrations: 0 µM, 0.1 µM, 1 µM and 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of caspase 3/7 and demonstrated PARP cleavage. Cell cycle analysis[1] Cell Types: HCT116 Cell Tested Concentrations: 0 µM, 0.01 µM, 0.1 µM, 1 µM and 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: Shows accumulation of G2/M cells. Western Blot Analysis[1] Cell Types: HCT116 Cell Tested Concentrations: 0 µM, 0.1 µM, 1 µM, and 10 µM Incubation Duration: 0 Hour, 4 Hour, 8 Hour, 16 Hour, or 24 Hour Experimental Results: PolII CTD Phosphorylation in HCT116 Colon dose- and time-dependent manner in cancer cells. |
Animal Protocol |
Animal/Disease Models: Female nu/nu-BALB/c athymic nude mice (7 weeks old) with MCF7 cells [1].
Doses: 100 mg/kg Route of Administration: po (oral gavage); daily; 14-day Experimental Results: On day 14, tumor growth was inhibited by 60%. |
References |
[1]. Patel H, et al. ICEC0942, an Orally Bioavailable Selective Inhibitor of CDK7 for Cancer Treatment. Mol Cancer Ther. 2018 Jun;17(6):1156-1166.
[2]. Hazel P, et al. Inhibitor Selectivity for Cyclin-Dependent Kinase 7: A Structural, Thermodynamic, and Modelling Study. ChemMedChem. 2017 Mar 7;12(5):372-380. |
Molecular Formula |
C22H30N6O
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Molecular Weight |
394.513204097748
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CAS # |
1805833-75-3
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Related CAS # |
Samuraciclib hydrochloride;1805789-54-1;Samuraciclib hydrochloride hydrate;Samuraciclib hydrochloride hydrate
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O[C@H]1CNCC[C@@H]1CNC2=NC3=C(C(C)C)C=NN3C(NCC4=CC=CC=C4)=C2
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InChi Key |
YCVGLKWJKIKVBI-MJGOQNOKSA-N
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InChi Code |
InChI=1S/C22H30N6O/c1-15(2)18-13-26-28-21(25-11-16-6-4-3-5-7-16)10-20(27-22(18)28)24-12-17-8-9-23-14-19(17)29/h3-7,10,13,15,17,19,23,25,29H,8-9,11-12,14H2,1-2H3,(H,24,27)/t17-,19+/m1/s1
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Chemical Name |
(3~{R},4~{R})-4-[[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol
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Synonyms |
ICEC0942 PPDA-001 GTPL9903CT 7001ICEC-0942 PPDA-001 GTPL-9903CT-7001ICEC 0942 CT7001 PPDA-001 GTPL
9903
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5348 mL | 12.6739 mL | 25.3479 mL | |
5 mM | 0.5070 mL | 2.5348 mL | 5.0696 mL | |
10 mM | 0.2535 mL | 1.2674 mL | 2.5348 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.