LDC000067

CDK9 inhibitor, novel and highly specific CAS# 1073485-20-7

LDC000067

Catalog No. BCC5452----Order now to get a substantial discount!

Product Name & Size Price Stock
LDC000067: 5mg $58 In Stock
LDC000067: 10mg Please Inquire In Stock
LDC000067: 20mg Please Inquire Please Inquire
LDC000067: 50mg Please Inquire Please Inquire
LDC000067: 100mg Please Inquire Please Inquire
LDC000067: 200mg Please Inquire Please Inquire
LDC000067: 500mg Please Inquire Please Inquire
LDC000067: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of LDC000067

Number of papers citing our products

Chemical structure

LDC000067

3D structure

Chemical Properties of LDC000067

Cas No. 1073485-20-7 SDF Download SDF
PubChem ID 25104564 Appearance Powder
Formula C18H18N4O3S M.Wt 370.43
Type of Compound N/A Storage Desiccate at -20°C
Synonyms LDC067
Solubility DMSO : ≥ 47 mg/mL (126.88 mM)
*"≥" means soluble, but saturation unknown.
Chemical Name [3-[[6-(2-methoxyphenyl)pyrimidin-4-yl]amino]phenyl]methanesulfonamide
SMILES COC1=CC=CC=C1C2=CC(=NC=N2)NC3=CC=CC(=C3)CS(=O)(=O)N
Standard InChIKey GGQCIOOSELPMBB-UHFFFAOYSA-N
Standard InChI InChI=1S/C18H18N4O3S/c1-25-17-8-3-2-7-15(17)16-10-18(21-12-20-16)22-14-6-4-5-13(9-14)11-26(19,23)24/h2-10,12H,11H2,1H3,(H2,19,23,24)(H,20,21,22)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of LDC000067

DescriptionLDC000067 is a highly specific CDK9 inhibitor with an IC50 value of 44±10 nM in vitro.In Vitro:The selectivity of LDC000067 for CDK9 over other CDKs exceeds that of the known inhibitors flavopiridol and DRB. LDC000067 displayed 55/125/210/ >227/ >227-fold selectivity for CDK9 versus CDK2/1/4/6/7. LDC000067 inhibits in vitro transcription in an ATP-competitive and dose-dependent manner. Gene expression profiling of cells treated with LDC000067 demonstrates a selective reduction of short-lived mRNAs, including important regulators of proliferation and apoptosis[1].

References:
[1]. Albert TK, et al. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br J Pharmacol. 2014 Jan;171(1):55-68.

Protocol

Kinase experiment [1]:

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]:

Cell lines

HEK293T cells, THP1 cells

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.

Reacting condition

Competitive kinase binding displacement assay: 90 min.DNA microarray analysis assay: 90 min.

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.

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.

LDC000067 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

LDC000067 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of LDC000067

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.6996 mL 13.4978 mL 26.9957 mL 53.9913 mL 67.4891 mL
5 mM 0.5399 mL 2.6996 mL 5.3991 mL 10.7983 mL 13.4978 mL
10 mM 0.27 mL 1.3498 mL 2.6996 mL 5.3991 mL 6.7489 mL
50 mM 0.054 mL 0.27 mL 0.5399 mL 1.0798 mL 1.3498 mL
100 mM 0.027 mL 0.135 mL 0.27 mL 0.5399 mL 0.6749 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on LDC000067

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.

Featured Products
New Products
 

References on LDC000067

Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor.[Pubmed:24102143]

Br J Pharmacol. 2014 Jan;171(1):55-68.

BACKGROUND AND PURPOSE: The cyclin-dependent kinase CDK9 is an important therapeutic target but currently available inhibitors exhibit low specificity and/or narrow therapeutic windows. Here we have used a new highly specific CDK9 inhibitor, LDC000067 to interrogate gene control mechanisms mediated by CDK9. EXPERIMENTAL APPROACH: The selectivity of LDC000067 was established in functional kinase assays. Functions of CDK9 in gene expression were assessed with in vitro transcription experiments, single gene analyses and genome-wide expression profiling. Cultures of mouse embryonic stem cells, HeLa cells, several cancer cell lines, along with cells from patients with acute myelogenous leukaemia were also used to investigate cellular responses to LDC000067. KEY RESULTS: The selectivity of LDC000067 for CDK9 over other CDKs exceeded that of the known inhibitors flavopiridol and DRB. LDC000067 inhibited in vitro transcription in an ATP-competitive and dose-dependent manner. Gene expression profiling of cells treated with LDC000067 demonstrated a selective reduction of short-lived mRNAs, including important regulators of proliferation and apoptosis. Analysis of de novo RNA synthesis suggested a wide ranging positive role of CDK9. At the molecular and cellular level, LDC000067 reproduced effects characteristic of CDK9 inhibition such as enhanced pausing of RNA polymerase II on genes and, most importantly, induction of apoptosis in cancer cells. CONCLUSIONS AND IMPLICATIONS: Our study provides a framework for the mechanistic understanding of cellular responses to CDK9 inhibition. LDC000067 represents a promising lead for the development of clinically useful, highly specific CDK9 inhibitors.

Description

LDC000067 is a highly specific CDK9 inhibitor with an IC50 value of 44±10 nM in vitro.

Keywords:

LDC000067,1073485-20-7,LDC067,Natural Products,Cyclin-Dependent Kinases, buy LDC000067 , LDC000067 supplier , purchase LDC000067 , LDC000067 cost , LDC000067 manufacturer , order LDC000067 , high purity LDC000067

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: