Physicochemical Properties
| Molecular Formula | C18H25FN6 |
| Molecular Weight | 344.429706335068 |
| Exact Mass | 344.212 |
| CAS # | 2079069-01-3 |
| PubChem CID | 134812748 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.4 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 25 |
| Complexity | 439 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1=CN=C(N=C1C1C=NN(C)C=1CC1CC1)NC1CCC(CC1)N |
| InChi Key | YSPIHUWHLMNFOV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H25FN6/c1-25-16(8-11-2-3-11)14(9-22-25)17-15(19)10-21-18(24-17)23-13-6-4-12(20)5-7-13/h9-13H,2-8,20H2,1H3,(H,21,23,24) |
| Chemical Name | 4-N-[4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]-5-fluoropyrimidin-2-yl]cyclohexane-1,4-diamine |
| 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 | CKIα CDK7 0.31 nM (Kd) CDK9 5.4 nM (Kd) |
| ln Vitro | At 160 nM or less, the casein kinase inhibitor A86 is very effective in causing leukemia cells to undergo apoptosis, primarily due to its ability to stabilize p53[1]. MYC, MDM2, and the anti-apoptotic oncogene MCL1 are all eliminated by the casein kinase inhibitor A86 (0.08-2 μM; 6.5 hours). The Wnt targets AXIN2 and CCND1 (Cyclin D1) are expressed more when the casein kinase inhibitor A86 is used, although the mRNA expression of MYC and MDM2 is significantly reduced[1]. |
| ln Vivo | Rapid oral absorption is shown in pharmacokinetic investigations with the Casein Kinase inhibitor A86 at 20 mg/kg, with Tmax values of 0.2-0.5 hours, Cmax values of 1115 ng/mL, T1/2 values of 4.3 hours, and area under the curve (AUC) values of 2606 (ng*hr/mL)[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: MV4-11 cells Tested Concentrations: 0.08 μM, 0.6 μM, 2 μM Incubation Duration: 6.5 hrs (hours) Experimental Results: Abolishes the expression of MYC, MDM2, and the anti-apoptotic oncogene MCL1. |
| References |
[1]. Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. Cell. 2018 Sep 20;175(1):171-185.e25. |
Solubility Data
| Solubility (In Vitro) | DMSO : 12.5 mg/mL (36.29 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.63 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 12.5 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: ≥ 1.25 mg/mL (3.63 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 12.5 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: ≥ 1.25 mg/mL (3.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 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 | 2.9033 mL | 14.5167 mL | 29.0335 mL | |
| 5 mM | 0.5807 mL | 2.9033 mL | 5.8067 mL | |
| 10 mM | 0.2903 mL | 1.4517 mL | 2.9033 mL |