LDC000067 (Synonyms: LDC067) |
| Katalog-Nr.GC17067 |
LDC000067 ist ein hochspezifischer CDK9-Inhibitor mit einem IC50-Wert von 44±10 nM in vitro.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1073485-20-7
Sample solution is provided at 25 µL, 10mM.
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LDC000067 (LDC067) is a novel specific inhibitor of CDK9 with IC50 value of 44 ± 10 nM [1].
Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase. CDK9 and cyclin T form the positive transcription elongation factor b (P-TEFb) complex for RNA polymerase II and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II [1].
LDC000067 (LDC067) is a novel and highly specific CDK9 inhibitor. LDC000067 exhibited selectivity for CDK9 over other CDKs in the range of 55-fold (vs. CDK2) to over 230-fold (vs. CDK6 and CDK7). LDC067 also inhibited transcription in a dose-dependent and ATP-competitive manner. In whole cells, LDC000067 induced the tumor suppressor protein p53 activation and apoptosis. LDC000067 also selectively reduced short-lived mRNAs, including those that encode regulators of apoptosis and proliferation such as MYC and MCL1 [1].
Reference:
[1]. Albert TK, Rigault C, Eickhoff J, et al. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br J Pharmacol, 2014, 171(1): 55-68.
| Kinase experiment [1]: | |
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Inhibitory activities |
Kinase inhibition by LDC000067 was measured in a radio metric assay, which directly measured kinase catalytic activity towards a specific substrate. Briefly, 10 μM LDC000067 or DMSO as solvent control, were added to base reaction buffer (10 mM MgCl2, 1 mM EDTA, 20 mM HEPES pH 7.5, 2 mM DTT, 0.02 mg·mL-1 BSA, 0.1 mM Na3VO4, 0.02% Brij35, 1% DMSO), containing cofactors and substrates, which were required by the individual kinase. 10 μCi of [γ-33P]-APP (10mCi·mL-1, 3000Ci·mmol-1, Perkin Elmer) was added to the reaction mixture. And such kinase reaction incubated for 120min at room temperature. Reactions were found on P81 ion exchange paper, and filters generally washed in 0.75% phosphoric acid before radiometric quantification. Each protein kinase was measured in duplicate, and its catalytic activity expressed as residual kinase activity, which shows the percentage of average substrate phophorylation in contrast with the solvent control reaction. |
| Cell experiment [1]: | |
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Cell lines |
HEK293T cells, THP1 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
Competitive kinase binding displacement assay: 90 min.DNA microarray analysis assay: 90 min. |
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Applications |
LDC000067 inhibits CDK9 with an IC50 value of 44(10 nM, and its selectivity for CDK9 over other CDKs is in the range of 55-fold to over 230-fold, especially higher selectivity in an ATP-competitive kinase binding assay. Besides, effects of LDC000067 in whole cells contain induction of the tumour suppressor protein p53 and apoptosis. Moreover, gene expression profiling of cells treated with LDC000067 demonstrate selective reduction of short-lived mRNAs, which encode regulators of proliferation and apoptosis, such as MCL1 and MYC. |
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References: [1]. T K Albert1, C Rigault1, J Eickhoff, K Baumgart, C Antrecht1, B Klebl, G Mittler and M Meisterernst. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. British Journal of Pharmacology. 2014, 171: 55–68. | |
| Cas No. | 1073485-20-7 | SDF | |
| Überlieferungen | LDC067 | ||
| Chemical Name | (3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methanesulfonamide | ||
| Canonical SMILES | COC1=CC=CC=C1C2=CC(NC3=CC=CC(CS(N)(=O)=O)=C3)=NC=N2 | ||
| Formula | C18H18N4O3S | M.Wt | 370.43 |
| Löslichkeit | ≥ 18.52mg/mL in DMSO | Storage | Desiccate at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6996 mL | 13.4978 mL | 26.9957 mL |
| 5 mM | 539.9 μL | 2.6996 mL | 5.3991 mL |
| 10 mM | 270 μL | 1.3498 mL | 2.6996 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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