| 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 |
CDK12 23.9 nM (IC50) CDK2/cyclinE 173 μM (IC50) CDK9/cyclinT1 127 μM (IC50)
CDK12-IN-5 targets cyclin-dependent kinase 12 (CDK12), a transcription-regulating kinase involved in DNA damage response and gene expression. The compound inhibits CDK12 with an IC50 of 23.9 nM at high ATP (2 mM). It is highly selective for CDK12 over CDK2/Cyclin E (IC50 = 173 μM) and CDK9/Cyclin T1 (IC50 = 127 μM) at high ATP. The compound has potential anticancer and antitumor activity. |
|---|---|
| ln Vitro |
In MDA-MB-231 cells, CDK12-IN-5 (Example 426) suppresses BRCA1 MRNA expression (IC50=3.23 nM), while having no effect on CAL-120 cells[1]. With MDA-MB-231 cells (IC50=4.19 nM) and CAL-120 cells (IC50=3.57 nM), CDK12-IN-5 exhibits antiproliferative activity[1]. The IC50 CDK12 high ATP to Degradation DC50 CDK12 ratio of CDK12-IN-5 is 32[1].
In vitro studies demonstrate that CDK12-IN-5 is a potent CDK12 inhibitor with an IC50 of 23.9 nM at high ATP (2 mM). The compound has no effect on CDK2/Cyclin E (IC50 = 173 μM) or CDK9/Cyclin T1 (IC50 = 127 μM) at high ATP. CDK12-IN-5 has potential anticancer and antitumor activity. The compound shows anti-proliferative activity with an IC50 of 3.57 nM. |
| ln Vivo |
CDK12-IN-5 has potential anticancer and antitumor activity and can be used orally in the study of breast and ovarian cancer. The compound is a potent CDK12 inhibitor that may have in vivo efficacy in cancer models. Its selectivity for CDK12 over other CDKs may contribute to a favorable safety profile. Further studies would be needed to evaluate its efficacy in various cancer models.
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| Enzyme Assay |
The CDK12 inhibitory activity of CDK12-IN-5 can be assessed using in vitro kinase assays. In a typical assay, recombinant CDK12 kinase is incubated with a peptide substrate, ATP (at 2 mM), and varying concentrations of CDK12-IN-5. The incorporation of phosphate into the substrate is measured, and the IC50 is calculated. The IC50 for CDK12 inhibition at high ATP is 23.9 nM. The selectivity against CDK2/Cyclin E and CDK9/Cyclin T1 is assessed using similar assays.
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| Cell Assay |
The cellular activity of CDK12-IN-5 is assessed using cancer cell lines. Cells are treated with escalating concentrations of CDK12-IN-5. Cell viability is measured using MTT or CellTiter-Glo assays. The compound shows anti-proliferative activity with an IC50 of 3.57 nM. CDK12 target engagement can be assessed by measuring downstream effects on transcription or DNA damage response. The compound's selectivity for CDK12 over other CDKs contributes to its cellular activity profile.
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| Animal Protocol |
CDK12-IN-5 has potential anticancer and antitumor activity and can be used orally in the study of breast and ovarian cancer. The compound is a potent CDK12 inhibitor that may have in vivo efficacy in cancer models. Further studies would be needed to evaluate its efficacy in xenograft models of breast and ovarian cancer.
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| ADME/Pharmacokinetics |
CDK12-IN-5 is orally active, indicating favorable oral bioavailability. The compound has a molecular weight of approximately 450 g/mol. It is a pyrazolotriazine derivative. The compound has an IC50/CDK12 to DC50/CDK12 ratio of 32. Further studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion properties, including half-life, Cmax, AUC, and tissue distribution.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for CDK12-IN-5. As a CDK12 inhibitor, it may have on-target effects on transcription and DNA damage response in normal cells. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound's selectivity for CDK12 over other CDKs may contribute to a favorable safety profile.
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| References | |
| Additional Infomation |
CDK12-IN-5 (CAS# 2651200-35-8) is a pyrazolotriazine that functions as a potent CDK12 inhibitor with an IC50 of 23.9 nM at high ATP (2 mM). It has no effect on CDK2/Cyclin E (173 μM) or CDK9/Cyclin T1 (127 μM) at high ATP. The compound has potential anticancer and antitumor activity and can be used orally in the study of breast and ovarian cancer. It shows anti-proliferative activity with an IC50 of 3.57 nM. The IC50/CDK12 to DC50/CDK12 ratio is 32.
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| Molecular Formula |
C18H15F5N8O
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|---|---|
| Molecular Weight |
454.356719255447
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| Exact Mass |
454.128
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| CAS # |
2651200-35-8
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| PubChem CID |
156482226
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| Appearance |
White to off-white solid powder
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
655
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N12N=CC(C(F)(F)F)=C1N=C(N1CCOCC1)N=C2NCC1NC2=C(F)C(F)=CC=C2N=1
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| InChi Key |
XFZQHKMIWRKKCU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H15F5N8O/c19-10-1-2-11-14(13(10)20)27-12(26-11)8-24-16-29-17(30-3-5-32-6-4-30)28-15-9(18(21,22)23)7-25-31(15)16/h1-2,7H,3-6,8H2,(H,26,27)(H,24,28,29)
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| Chemical Name |
N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-2-morpholin-4-yl-8-(trifluoromethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine
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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 : 125 mg/mL (275.11 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.58 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (4.58 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 20.8 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 | 2.2009 mL | 11.0045 mL | 22.0090 mL | |
| 5 mM | 0.4402 mL | 2.2009 mL | 4.4018 mL | |
| 10 mM | 0.2201 mL | 1.1004 mL | 2.2009 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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