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| Targets |
AZ5576 targets cyclin-dependent kinase 9 (CDK9), a key regulator of transcriptional elongation. CDK9 phosphorylates RNA polymerase II at Ser2, which is essential for productive transcription elongation. By inhibiting CDK9, AZ5576 blocks transcriptional elongation, leading to reduced expression of short-lived anti-apoptotic proteins such as Mcl-1. This mechanism makes it a valuable tool for studying transcriptional regulation and for developing cancer therapeutics.
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| ln Vitro |
In vitro, AZ5576 is a potent and highly selective CDK9 inhibitor with an IC50 of <5 nM. It inhibits the phosphorylation of RNA polymerase II at Ser2, thereby inhibiting transcriptional elongation. Its activity is concentration-dependent, with effective concentrations in the nanomolar range. Its potent and selective CDK9 inhibition makes it a valuable tool for studying CDK9 biology and for developing cancer therapeutics.
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| ln Vivo |
In vivo, AZ5576 has been studied in preclinical models of hematological malignancies. Its ability to inhibit CDK9 and block transcriptional elongation may lead to antitumor effects. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources.
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| Enzyme Assay |
The in vitro CDK9 inhibition assay for AZ5576 typically uses purified CDK9/cyclin T1 complex and a peptide substrate. The assay is performed in 96-well plates with ATP, the substrate, and varying concentrations of the test compound (typically 0.01 nM to 10 µM). The reaction is initiated by adding ATP and incubated at 30°C for 30-60 minutes. Phosphorylated substrate is detected using a phospho-specific antibody in an ELISA format. IC50 values are calculated from dose-response curves using nonlinear regression.
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| Cell Assay |
For in vitro cellular assays, hematological cancer cell lines are treated with AZ5576 at concentrations ranging from 0.01 nM to 10 µM for 24-72 hours. Cell viability is assessed using CellTiter-Glo or MTT assays. RNA polymerase II phosphorylation (Ser2) is assessed by Western blotting. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are inoculated with hematological cancer cells. When tumors are established, mice are randomized into treatment groups. AZ5576 is administered orally or intraperitoneally at doses ranging from 1 to 50 mg/kg. Tumor volume is measured, and survival is assessed. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of AZ5576 have been partially characterized. The compound has a molecular weight of 385.43. Following oral administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 4-8 hours. The compound distributes into tissues including tumor, liver, and kidney.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of AZ5576 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses.
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| References | |
| Additional Infomation |
AZ5576 is a potent and highly selective CDK9 inhibitor with an IC50 of <5 nM. It has a molecular formula of C21H24FN3O3 and a molecular weight of 385.43. AZ5576 inhibits RNA polymerase II phosphorylation and can be used for hematological malignancy research. It is not approved for human use and has not entered clinical trials.
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| Molecular Formula |
C21H24FN3O3
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|---|---|
| Molecular Weight |
385.43
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| Exact Mass |
385.18
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| Elemental Analysis |
C, 65.44; H, 6.28; F, 4.93; N, 10.90; O, 12.45
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| CAS # |
2751721-40-9
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| Related CAS # |
1333468-12-4 (1R3S-isomer);2751721-40-9 (1S3R-isomer);1333468-05-5 (racemate);
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| PubChem CID |
53373586
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
547
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C1C=C(F)C=CC=1C1=CC=NC(NC([C@H]2CCC[C@@H](NC(=O)C)C2)=O)=C1)C
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| InChi Key |
QNWXRLPZIFMTBK-DOTOQJQBSA-N
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| InChi Code |
InChI=1S/C21H24FN3O3/c1-13(26)24-17-5-3-4-15(10-17)21(27)25-20-11-14(8-9-23-20)18-7-6-16(22)12-19(18)28-2/h6-9,11-12,15,17H,3-5,10H2,1-2H3,(H,24,26)(H,23,25,27)/t15-,17+/m0/s1
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| Chemical Name |
(1S,3R)-3-acetamido-N-[4-(4-fluoro-2-methoxyphenyl)pyridin-2-yl]cyclohexane-1-carboxamide
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| Synonyms |
AZ-5576AZ5576AZ 5576
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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 (~324.31 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.40 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 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 (5.40 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 | 2.5945 mL | 12.9725 mL | 25.9450 mL | |
| 5 mM | 0.5189 mL | 2.5945 mL | 5.1890 mL | |
| 10 mM | 0.2595 mL | 1.2973 mL | 2.5945 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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