Atuveciclib racemate

Alias: BAY1143572 S-Enantiomer; BAY 1143572 S-Enantiomer; BAY-1143572S-Enantiomer
Cat No.:V3689 Purity: ≥98%
Atuveciclib racemate (formerly BAY-1143572 racemate) is the racemic mixture of Atuveciclib, which is novel, potent, oral and highly selective PTEFb/CDK9 inhibitor currently in Phase I clinical trial to treat cancer.
Atuveciclib racemate Chemical Structure CAS No.: 1414943-88-6
Product category: CDK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
5mg
10mg
25mg
50mg
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Other Forms of Atuveciclib racemate:

  • Atuveciclib (BAY-1143572)
  • Atuveciclib S-Enantiomer (BAY-1143572 S-Enantiomer)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Atuveciclib racemate (formerly BAY-1143572 racemate) is the racemic mixture of Atuveciclib, which is novel, potent, oral and highly selective PTEFb/CDK9 inhibitor currently in Phase I clinical trial to treat cancer. With an IC50 of 385 nM, it prevents AML cell lines from proliferating. Moreover, it inhibits GSK3 kinase, with IC50 values for GSK3α and GSK3β of 45 nM and 87 nM, respectively.

Biological Activity I Assay Protocols (From Reference)
Targets
CDK9 (IC50 = 13 nM); GSK-3α (IC50 = 45 nM); GSK3β (IC50 = 87 nM)
ln Vitro

Atuveciclib (BAY-1143572) induces apoptosis and has a median IC50 of 385 nM (range 230-1100 nM), which inhibits the proliferation of seven AML cell lines that are positive and negative for MLL rearrangements[1]. With a minimum of 50-fold selectivity against other CDKs, atuveciclib (BAY-1143572) exhibits strong and highly selective PTEFb-kinase inhibitory activity in the low nanomolar range against PTEFb/CDK9. A panel of non-CDK kinases exhibits good selectivity towards ateveciclib (BAY-1143572). With IC50 values that are sub-micromolar, it exhibits broad antiproliferative activity against a panel of tumor cell lines. Concentration-dependent inhibition of RNA polymerase II phosphorylation is observed, followed by a downstream decrease in MYC mRNA and protein levels[2].

ln Vivo
Atuveciclib (BAY-1143572), when taken orally once daily, shows single agent efficacy at tolerated doses in 4 out of 5 AML xenograft tumor models in mice and in 2 out of 2 AML xenograft tumor models in rats. In a number of models, partial or even total remissions could be accomplished[1]. Blood cells from rats treated with Atuveciclib (BAY-1143572) also show inhibition of MYC mRNA, suggesting the potential clinical use of MYC in blood cells as a pharmacodynamic marker in clinical development. When combined with multiple chemotherapeutics, the in vivo efficacy of Atuveciclib (BAY-1143572) is markedly increased in various solid tumor models[2].
Animal Protocol

Immunocompromized NOD/Shi-scid/IL-2Rγ null (NOG) mice xenografted with patient-derived ATL cells and in vivo pharmacokinetic in rats
References

[1]. BAY 1143572, a first-in-class, highly selective, potent and orally available inhibitor of PTEFb/CDK9 currently in Phase I, shows convincing anti-tumor activity in preclinical models of acute myeloid leukemia (AML).

[2]. BAY 1143572: A first-in-class, highly selective, potent and orally available inhibitor of PTEFb/CDK9 currently in Phase I, inhibits MYC and shows convincing anti-tumor activity in multiple xenograft models by the induction of apoptosis.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C18H18FN5O2S
Molecular Weight
387.43
Exact Mass
387.12
Elemental Analysis
C, 55.80; H, 4.68; F, 4.90; N, 18.08; O, 8.26; S, 8.27
CAS #
1414943-88-6
Related CAS #
Atuveciclib;2923012-24-0;Atuveciclib S-Enantiomer;2250279-81-1
Appearance
Solid powder
SMILES
COC1=C(C=CC(=C1)F)C2=NC(=NC=N2)NC3=CC=CC(=C3)CS(=N)(=O)C
InChi Key
ACWKGTGIJRCOOM-UHFFFAOYSA-N
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)
Chemical Name
4-(4-fluoro-2-methoxyphenyl)-N-[3-[(methylsulfonimidoyl)methyl]phenyl]-1,3,5-triazin-2-amine
Synonyms
BAY1143572 S-Enantiomer; BAY 1143572 S-Enantiomer; BAY-1143572S-Enantiomer
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: >100 mg/mL
Water: <1mg/mL
Ethanol: <1mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.45 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 25.0 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: ≥ 2.5 mg/mL (6.45 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 25.0 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.45 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 25.0 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 2.5811 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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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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