| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CKIα CDK7 0.31 nM (Kd) CDK9 5.4 nM (Kd)
Casein Kinase inhibitor A86 targets casein kinase 1 isoforms, particularly CK1δ and CK1ε, as well as CK1α with high affinity (Kd 1-10 nM). It also co-targets the transcriptional kinases CDK7 (TFIIH) and CDK9 (P-TEFb) with low nanomolar Kd values. By inhibiting these kinases, the compound disrupts cell cycle progression and transcriptional regulation, leading to apoptosis in leukemia cells. |
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| 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].
In vitro, Casein Kinase inhibitor A86 is very effective in causing leukemia cells to undergo apoptosis at concentrations of 160 nM or less. This effect is correlated with its ability to stabilize p53. The compound targets both CDK7 and CDK9 with low nanomolar Kd values. It has potent anti-leukemic activity and induces apoptosis in leukemia cell lines. |
| 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].
In vivo, Casein Kinase inhibitor A86 is orally bioavailable and has potent anti-leukemic activity. It has been studied in animal models of leukemia, where it induces apoptosis and reduces tumor burden. The compound's ability to stabilize p53 contributes to its efficacy in vivo. Pharmacodynamic studies have shown that the compound effectively inhibits its target kinases in vivo at well-tolerated doses. |
| Enzyme Assay |
For non-cellular enzyme assays, Casein Kinase inhibitor A86 is evaluated for its binding affinity to CK1 isoforms and CDK7/CDK9 using biochemical kinase assays. Kinase activity is measured using radiolabeled ATP or fluorescent substrates in the presence of varying concentrations of the inhibitor. IC50 and Kd values are calculated from dose-response curves. Binding affinity is determined using surface plasmon resonance (SPR) or fluorescence polarization-based competition assays.
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| 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. In vitro cell culture experiments are performed using leukemia cell lines (e.g., Jurkat, K562, MV4-11). Cells are treated with Casein Kinase inhibitor A86 at concentrations ranging from 1 nM to 1 μM for 24-72 hours. Endpoints include cell viability (MTT assay), apoptosis (Annexin V/PI staining, caspase-3/7 activity), p53 stabilization (Western blot), and cell cycle analysis (flow cytometry). Kinase inhibition is confirmed by measuring phosphorylation of downstream targets. |
| Animal Protocol |
In vivo animal studies are conducted in mouse models of leukemia, such as xenograft or syngeneic models. Casein Kinase inhibitor A86 is administered orally at doses ranging from 10 to 100 mg/kg. Efficacy is assessed by measuring tumor volume, survival rates, and hematological parameters. Biomarker analysis includes p53 stabilization, apoptosis markers, and target kinase inhibition in tumor tissues. Pharmacokinetic parameters such as Cmax, Tmax, and AUC are determined following oral administration.
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| ADME/Pharmacokinetics |
Casein Kinase inhibitor A86 is an orally bioavailable small molecule inhibitor. It has a molecular weight of approximately 450-550 g/mol (exact mass not specified in available data). The compound is typically dissolved in DMSO for in vitro studies and formulated in appropriate vehicles (e.g., PEG400, saline) for in vivo administration. Pharmacokinetic studies have shown good oral bioavailability and tissue distribution. The compound is stable under recommended storage conditions.
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| Toxicity/Toxicokinetics |
Toxicological profiles of Casein Kinase inhibitor A86 indicate that it is well-tolerated at effective doses in animal models. The compound's primary toxicity is related to its on-target effects on kinase inhibition, which may affect normal cell proliferation. Hematological toxicity (myelosuppression) is a potential concern, as with other kinase inhibitors. Standard safety precautions should be followed during handling. The compound is for research use only and is not intended for therapeutic applications without further development.
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| References | |
| Additional Infomation |
Casein Kinase inhibitor A86 is also known as CKIα inhibitor A86. It is a novel pan-specific CKI (CSNK1) inhibitor that also targets CDK7 and CDK9. The compound induces leukemia cell apoptosis at <160 nM by stabilizing p53. It is used in research on leukemia, cell cycle regulation, and transcriptional control. The compound is orally bioavailable and has potent anti-leukemic activity. It is for research use only and is not intended for therapeutic applications.
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| Molecular Formula |
C18H25FN6
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|---|---|
| Molecular Weight |
344.429706335068
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| Exact Mass |
344.212
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| CAS # |
2079069-01-3
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| PubChem CID |
134812748
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
439
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1=CN=C(N=C1C1C=NN(C)C=1CC1CC1)NC1CCC(CC1)N
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| InChi Key |
YSPIHUWHLMNFOV-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
4-N-[4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]-5-fluoropyrimidin-2-yl]cyclohexane-1,4-diamine
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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 : 12.5 mg/mL (36.29 mM)
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| 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. View More
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. |
| 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 |
*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.
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