| 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 |
IC50: 16 nM (CDK9/CycT1)[1]
The primary molecular target of Atuveciclib S-Enantiomer is the cyclin-dependent kinase 9 (CDK9), specifically in complex with its regulatory partner cyclin T1 (CDK9/CycT1). This complex is known as P-TEFb (positive transcription elongation factor b). The compound inhibits this protein complex with an IC50 of 16 nM. It is a potent and selective CDK9 inhibitor, showing negligible activity against a broad panel of other kinases. |
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| ln Vitro |
While Atuveciclib (BAY-1143572) S-Enantiomer and Atuveciclib (BAY-1143572) show very similar in vitro properties, well within the measurement accuracy bounds, there is a tendency toward slightly lower activity against CDK9 in the biochemical assay (IC50 CDK9/CycT1: 16 nM) and antiproliferative activity against HeLa cells (IC50: 1100 nM) with multiple batches of Atuveciclib (BAY-1143572) S-Enantiomer [1].
In vitro, Atuveciclib S-Enantiomer shows strong antiproliferative activity against cancer cell lines, with an IC50 of 1100 nM for HeLa cells and 310 nM for MOLM-13 cells (as reported for the racemate). It demonstrates very similar in vitro properties to its parent compound, Atuveciclib, but may show a trend toward slightly lower activity against CDK9 in biochemical assays. It potently inhibits the phosphorylation of RNA Polymerase II at Ser2, a key step in transcriptional elongation. |
| ln Vivo |
The blood/plasma ratios of the S-Enantiomer of Atuveciclib (BAY-1143572) are approximately 1. Atuveciclib (BAY-1143572) S-Enantiomer has remarkably similar rat PK characteristics in vivo (t1/2: 0.6 h, F: 53%, Vss: 1.2 L/kg, and CLb: 1.2 L/kg per hour) in comparison to Atuveciclib (BAY-1143572)[1].
In vivo, Atuveciclib S-Enantiomer has been evaluated in xenograft mouse models. The parent compound (BAY-1143572) demonstrated potent and good anticancer activity in the MOLM-13 xenograft model. The S-Enantiomer is expected to have similar in vivo properties. Atuveciclib is a well-known clinical CDK9 inhibitor, and this enantiomer is used as a reference compound for comparison in research settings. |
| Enzyme Assay |
For a cell-free system, a biochemical radiometric or luminescent assay is used. Purified CDK9/CycT1 enzyme, a peptide substrate (derived from RNA Polymerase II), and ATP (with gamma-33P-ATP for radioactive assays) are incubated. The compound is added to the reaction. After the reaction, the phosphorylated peptide is captured, and the incorporated radioactivity (or luminescence) is measured. The IC50 is calculated based on the reduction in kinase activity.
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| Cell Assay |
In cellular assays, cancer cells (e.g., HeLa or MOLM-13) are seeded in 96-well plates. The cells are treated with serial dilutions of Atuveciclib S-Enantiomer (e.g., 1 nM to 100 uM) for 72 hours. Cell viability is measured using a luminescence-based CellTiter-Glo assay. Mechanistically, the inhibition of CDK9 activity is confirmed by Western blotting, using a phospho-specific antibody (e.g., p-RNA Pol II Ser2) to detect a reduction in the target phosphorylation.
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| Animal Protocol |
For in vivo efficacy studies, female NOD-SCID mice are subcutaneously implanted with MOLM-13 human acute myeloid leukemia cells. Once tumors are established, mice are randomized and treated with Atuveciclib S-Enantiomer. The compound is typically administered by oral gavage (p.o.) at a specific dose (e.g., 50 mg/kg) on a daily or twice-daily schedule. Tumor volume is measured with calipers, and tumor growth inhibition (TGI) is calculated at the end of the study.
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| ADME/Pharmacokinetics |
In vivo rat pharmacokinetic (PK) studies show that Atuveciclib S-Enantiomer has a half-life (t1/2) of 0.6 hours, a steady-state volume of distribution (Vss) of 1.2 L/kg, and a clearance (CLb) of 1.2 L/kg per hour. It shows a blood-to-plasma ratio of about 1, indicating no preferential partitioning. Its oral bioavailability (F) is 53%. These properties suggest it is rapidly absorbed and cleared.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for this specific enantiomer is not presented, but it is a close analogue of the clinical CDK9 inhibitor Atuveciclib. As a CDK9 inhibitor, its pharmacological effects involve reducing the expression of short-lived anti-apoptotic proteins, which is the basis for its anticancer activity but could also lead to on-target toxicities. Detailed toxicology reports are not part of the provided summaries, as it is primarily a research reference compound.
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| References | |
| Additional Infomation |
Atuveciclib (BAY-1143572), the parent compound, is the first potent and highly selective PTEFb/CDK9 inhibitor to enter human clinical trials for the treatment of cancer. The (S)-Enantiomer is used as a reference standard for analytical and biological testing. While the parent drug has advanced into Phase I clinical studies, this specific enantiomer form is a research tool used for comparative studies to understand the properties of the racemate. It has not been approved for therapeutic use.
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| Molecular Formula |
C18H18FN5O2S
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|---|---|
| Molecular Weight |
387.431225299835
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| Exact Mass |
387.116
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| Elemental Analysis |
C, 55.80; H, 4.68; F, 4.90; N, 18.08; O, 8.26; S, 8.27
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| CAS # |
2250279-81-1
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| Related CAS # |
Atuveciclib Racemate;1414943-88-6;Atuveciclib;2923012-24-0
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| PubChem CID |
71618220
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| Appearance |
White to off-white solid at room temperature
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| LogP |
4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
588
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C)(CC1C=CC=C(C=1)NC1N=CN=C(C2C=CC(=CC=2OC)F)N=1)(=N)=O
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| InChi Key |
ACWKGTGIJRCOOM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H18FN5O2S/c1-26-16-9-13(19)6-7-15(16)17-21-11-22-18(24-17)23-14-5-3-4-12(8-14)10-27(2,20)25/h3-9,11,20H,10H2,1-2H3,(H,21,22,23,24)
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| Chemical Name |
4-(4-fluoro-2-methoxyphenyl)-N-[3-[(methylsulfonimidoyl)methyl]phenyl]-1,3,5-triazin-2-amine
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| Synonyms |
Atuveciclib S-Enantiomer; 2250279-81-1; BAY-1143572 S-Enantiomer; (S)-ATUVECICLIB; CHEMBL4560679;
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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: ≥ 113 mg/mL (291.7 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5811 mL | 12.9056 mL | 25.8111 mL | |
| 5 mM | 0.5162 mL | 2.5811 mL | 5.1622 mL | |
| 10 mM | 0.2581 mL | 1.2906 mL | 2.5811 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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