| Size | Price | Stock | Qty |
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| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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Purity: ≥98%
AZD4573 (AZD-4573) is a novel, potent and short acting inhibitor of serine/threonine CDK9 (cyclin-dependent kinase 9, IC50<0.004 μM) with potential anticancer activities. It has strong selectivity against other kinases, including those in the CDK family, and fast-off binding kinetics (t1/2 = 16 min). A variety of anti-apoptotic proteins' gene transcription is inhibited when AZD4573 binds to CDK9 and inhibits its phosphorylation and kinase activity. This prevents PTEFb-mediated activation of RNA Pol II.
| Targets |
CDK9 (IC50 = 4 nM)
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|---|---|
| ln Vitro |
AZD4573 treatment for a brief period of time resulted in a fast dose- and time-dependent reduction in cellular pSer2-RNAPII, which in turn activated caspase 3 and induced cell death in a variety of haematological cancer cell lines (for example, caspase activation EC50 13.7 nM in an acute myeloid leukemia model MV4-11) [1].
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| ln Vivo |
AZD4573 has a short half-life (less than an hour in the case of rats, dogs, and monkeys) and is well soluble when administered intravenously[1].
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| Cell Assay |
Specific drug concentrations were applied to the cells.
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| Animal Protocol |
Nomo-1 AML xenograft
5 mg/kg i.p. |
| References | |
| Additional Infomation |
Zemirciclib is a selective, short-acting inhibitor of the serine/threonine cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the RNA polymerase II (RNA Pol II) elongation factor positive transcription elongation factor b (PTEF-b; PTEFb), with potential antineoplastic activity. Upon intravenous administration, zemirciclib binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II, leading to the inhibition of gene transcription of various anti-apoptotic proteins. This induces cell cycle arrest and apoptosis, and leads to a reduction in tumor cell proliferation. CDK9 regulates elongation of transcription through phosphorylation of RNA polymerase II at serine 2 (p-Ser2-RNAPII). It is upregulated in various tumor cell types and plays a key role in the regulation of Pol II-mediated transcription of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.
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| Molecular Formula |
C22H28CLN5O2
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|---|---|---|
| Molecular Weight |
429.9430
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| Exact Mass |
429.19
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| Elemental Analysis |
C, 61.46; H, 6.56; Cl, 8.25; N, 16.29; O, 7.44
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| CAS # |
2057509-72-3
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| Related CAS # |
2057509-72-3;Unknown (HCl);
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| PubChem CID |
124155204
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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 |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
659
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC(=O)N[C@@H]1CCC[C@@H](C1)C(=O)NC2=NC=C(C(=C2)C3=C4CC(CN4N=C3)(C)C)Cl
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| InChi Key |
AVIWDYSJSPOOAR-LSDHHAIUSA-N
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| InChi Code |
InChI=1S/C22H28ClN5O2/c1-13(29)26-15-6-4-5-14(7-15)21(30)27-20-8-16(18(23)11-24-20)17-10-25-28-12-22(2,3)9-19(17)28/h8,10-11,14-15H,4-7,9,12H2,1-3H3,(H,26,29)(H,24,27,30)/t14-,15+/m0/s1
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| Chemical Name |
(1S,3R)-3-acetamido-N-[5-chloro-4-(5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazol-3-yl)pyridin-2-yl]cyclohexane-1-carboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.84 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 (4.84 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 20.8 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: ≥ 2.08 mg/mL (4.84 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 | 2.3259 mL | 11.6295 mL | 23.2591 mL | |
| 5 mM | 0.4652 mL | 2.3259 mL | 4.6518 mL | |
| 10 mM | 0.2326 mL | 1.1630 mL | 2.3259 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05140382 | Active Recruiting |
Drug: AZD4573 | Relapsed/Refractory Peripheral T-cell Lymphoma Relapsed/Refractory Classical Hodgkins Lymphoma |
AstraZeneca | December 15, 2021 | Phase 2 |
| NCT04630756 | Active Recruiting |
Drug: AZD4573 Drug: Acalabrutinib |
Advanced Haematological Malignancies |
AstraZeneca | February 17, 2021 | Phase 1 Phase 2 |
| NCT03263637 | Completed | Drug: AZD4573 | Richter's Syndrome Multiple Myeloma |
AstraZeneca | October 24, 2017 | Phase 1 |
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