Size | Price | |
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100mg | ||
250mg | ||
500mg | ||
Other Sizes |
Targets |
pIC50: 6.1 (BRD4), 6.3 (BRD2), 6.6 (BRD3)[1]
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ln Vitro |
Following a 72-hour treatment with 1 μM dihydrochloride I-BET151, the majority of living cells were shown to be in the G0 phase, which was correlated with a dose- and time-dependent reduction in cell proliferation and an abrogation of bromodeoxyuridine incorporation[2]. The percentage of myeloma cells in the S/G2 phase is significantly reduced by I-BET151 dihydrochloride (100 nM; 72 hours) in a dose- and time-dependent manner[2].
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ln Vivo |
I-BET151 dihydrochloride exhibits good oral systemic exposure, leading to good oral bioavailability, and poor blood clearance in rats (~20% liver blood flow). In the dog, there is high clearance (around 95% liver blood flow). The dog has a limited systemic exposure, which leads to a poor oral bioavailability of 16%. While the low intrinsic clearances in rat and mouse (mouse IVC 1.6 mL/min/g; CLb 8 mL/min/kg) coincide with lower in vivo blood clearances in these species, the high blood clearance in dogs is closely correlated with the high intrinsic clearance seen in dog microsomes and hepatocytes. I-BET151 dihydrochloride was examined in the mini-pig as a possible second species for toxicological study because of the dog's low systemic exposure, which was noted to have low clearance (~32% liver blood flow) and good bioavailability (65%)[1]. Compared to mice treated with vehicle, mice treated with I-BET151 dihydrochloride (30 mg/kg; ip; daily for 21 days) had myeloma tumors that were four to five times smaller and the rate of tumor size doubling was much lower[2].
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Cell Assay |
Cell Viability Assay[2]
Cell Types: H929 cells Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Displays the majority of live cells resided in the G0 phase and commensurate with a dose- and time-dependent decrease in cell proliferation and abrogation of bromodeoxyuridine incorporation. Cell Proliferation Assay[2] Cell Types: H929 cells Tested Concentrations: 100 nM Incubation Duration: 72 hrs (hours) Experimental Results: Caused a significant dose- and time-dependent decrease in the proportion of myeloma cells in S/ G2 phase. |
Animal Protocol |
Animal/Disease Models: Mice (model of subcutaneous (sc)myeloma)[2]
Doses: 50 mg/kg Route of Administration: Ip; daily for 21 days Experimental Results: diminished rate of tumor size doubling than vehicle-treated mice. |
References |
[1]. Seal J, et al. Identification of a novel series of BET family bromodomain inhibitors: Binding mode and profile of I-BET151 (GSK1210151A). Bioorg Med Chem Lett. 2012 Apr 15;22(8):2968-72.
[2]. Chaidos A, et al. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762. Blood. 2014 Jan 30;123(5):697-705. |
Molecular Formula |
C23H23CL2N5O3
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Molecular Weight |
488.37
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CAS # |
1883545-47-8
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Related CAS # |
I-BET151;1300031-49-5
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SMILES |
[C@@H](C1N=CC=CC=1)(N1C(NC2C=NC3=CC(C4=C(ON=C4C)C)=C(OC)C=C3C1=2)=O)C.Cl
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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.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0476 mL | 10.2381 mL | 20.4763 mL | |
5 mM | 0.4095 mL | 2.0476 mL | 4.0953 mL | |
10 mM | 0.2048 mL | 1.0238 mL | 2.0476 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.