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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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BAY-1251152 is a potent and highly selective PTEF/CDK9 inhibitor. BAY-1251152 exhibits high permeability, no efflux, enhanced selectivity against CDK2, and significantly increased biochemical (IC50 CDK9 = 3 nM) and cellular potency (IC50 MOLM13 = 29 nM). BAY 1251152's high solubility and much lower therapeutic dose allow for the intended intravenous application. BAY 1251152 exhibited remarkable effectiveness when administered intravenously (i.v.) to mice and rats in xenograft models, such as MOLM13. In Phase I studies (NCT02635672; NCT02745743), BAY 1251152 is presently being assessed for safety, tolerability, pharmacokinetics, and initial pharmacodynamic biomarker response in patients with advanced cancer. In a variety of tumor entities, including AML, PTEFb/CDK9 mediated transcription of short-lived anti-apoptotic survival proteins like Mcl-1 and Myc is essential for cancer cell growth and survival. Furthermore, these survival proteins are crucial in the process of chemotherapy resistance developing.
Targets |
CDK9/CycT1 (IC50 = 3 nM)
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ln Vitro |
BAY 1251152 (compound 2) has an IC50 of 3 nM and 360 nM, respectively, which indicates a significant inhibition of CDK9 and CDK2. With an IC50 of 29 nM, compound 2, BAY 1251152, demonstrates cellular potency in MOLM13.[1][2]
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ln Vivo |
BAY 1251152 xhibits remarkable efficacy when administered intravenously in xenograft models (e.g. MOLM13) in mice and rats. Phase I studies are currently being conducted on BAY 1251152 to assess its safety, tolerability, pharmacokinetics, and initial pharmacodynamic biomarker response in patients with advanced cancer.[2]
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Cell Assay |
In a 96-well multititer plate, 200 of the appropriate growth medium are added, along with 10% fetal calf serum, to cultivate tumor cells. The test substances are added to the fresh culture medium (200 μl) in the other plates in different concentrations (0 μM, as well as in the range of 0.001 -10 μM); the final concentration of the solvent dimethyl sulfoxide is 0.5%). After a 24-hour period, the cells on one plate (the zero-point plate) are stained with crystal violet. The test substances are present while the cells are incubated for four days.
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Animal Protocol |
mice and rats with xenograft models (eg. MOLM13)
IV |
References |
Molecular Formula |
C19H18F2N4O2S
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Molecular Weight |
404.4336
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Exact Mass |
404.11185333
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Elemental Analysis |
C, 56.43; H, 4.49; F, 9.40; N, 13.85; O, 7.91; S, 7.93
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CAS # |
1610358-56-9
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Related CAS # |
(±)-Enitociclib;1610358-53-6;(-)-Enitociclib;1610358-59-2
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Appearance |
Solid powder
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SMILES |
COC1=C(C=CC(=C1)F)C2=CC(=NC=C2F)NC3=NC=CC(=C3)CS(=N)(=O)C
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InChi Key |
YZCUMZWULWOUMD-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C19H18F2N4O2S/c1-27-17-8-13(20)3-4-14(17)15-9-19(24-10-16(15)21)25-18-7-12(5-6-23-18)11-28(2,22)26/h3-10,22H,11H2,1-2H3,(H,23,24,25)
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Chemical Name |
5-fluoro-4-(4-fluoro-2-methoxyphenyl)-N-[4-[(methylsulfonimidoyl)methyl]pyridin-2-yl]pyridin-2-amine
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Synonyms |
(-)-BAY-1251152; BAY-1251152; BAY 1251152; BAY1251152; (+)-BAY-1251152
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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) |
DMSO: 81~113.3 mg/mL (200.3~280.2 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.18 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 (6.18 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 (6.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4726 mL | 12.3631 mL | 24.7262 mL | |
5 mM | 0.4945 mL | 2.4726 mL | 4.9452 mL | |
10 mM | 0.2473 mL | 1.2363 mL | 2.4726 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.