(-)-BAY-1251152, the enanthiomer of BAY-1251152 which 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. The transcription of myc and Mcl-1, two short-lived anti-apoptotic survival proteins, is mediated by PTEFb/CDK9 and is essential for the growth and survival of cancer cells in a variety of tumor types, including AML. Furthermore, the development of chemotherapy resistance is significantly influenced by these survival proteins.
Physicochemical Properties
| Molecular Formula | C19H18F2N4O2S |
| Molecular Weight | 404.433629512787 |
| Exact Mass | 404.111 |
| CAS # | 1610358-59-2 |
| Related CAS # | Enitociclib;1610358-56-9;(±)-Enitociclib;1610358-53-6 |
| PubChem CID | 74767009 |
| Appearance | Off-white to light yellow solid |
| LogP | 4.2 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 28 |
| Complexity | 619 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | YZCUMZWULWOUMD-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 5-fluoro-4-(4-fluoro-2-methoxyphenyl)-N-[4-[(methylsulfonimidoyl)methyl]pyridin-2-yl]pyridin-2-amine |
| Synonyms | (-)-BAY-1251152; BAY-1251152; BAY 1251152; BAY1251152; (+)-BAY-1251152. |
| 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 |
| 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
| Targets | CDK9 |
| References |
[1]. Identification of potent and highly selective PTEFb inhibitor BAY 1251152 for the treatment of cancer: from p.o. to i.v. application via scaffold hops. AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 984. doi:10.1158/1538-7445.AM2017-984. |
| Additional Infomation | See also: Enitociclib (annotation moved to). |
Solubility Data
| Solubility (In Vitro) | DMSO: ~22 mg/mL (~54.4 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.2 mg/mL (5.44 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 22.0 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: 2.2 mg/mL (5.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.0 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: 2.2 mg/mL (5.44 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |