LDC000067 (LDC067)

Alias: LDC067; LDC000067; LDC-000067; LDC-067; LDC 067; LDC 000067
Cat No.:V1544 Purity: ≥98%
LDC000067 (also called LDC-000067;LDC-067) is a novel, potent, highly selective and ATP-competitive inhibitor ofcyclin-dependent kinase (CDK9)with potential antineoplastic activity.
LDC000067 (LDC067) Chemical Structure CAS No.: 1073485-20-7
Product category: CDK
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

LDC000067 (also called LDC-000067; LDC-067) is a novel, potent, highly selective and ATP-competitive inhibitor of cyclin-dependent kinase (CDK9) with potential antineoplastic activity. With an IC50 of 44 nM, it suppresses CDK9. While CDK9 is a significant and highly effective therapeutic target for anticancer medications, the inhibitors that are currently on the market have limited therapeutic windows and/or low specificity. LDC000067 demonstrated a range of selectivity for CDK9 over other CDKs, from over 230-fold (versus CDK6 and CDK7) to 55-fold (versus CDK2). Additionally, LDC067 inhibited transcription in an ATP-competitive and dose-dependent manner. LDC000067 triggered apoptosis and the activation of the tumor suppressor protein p53 in whole cells. Additionally, LDC000067 specifically lowered short-lived mRNAs, such as MYC and MCL1, which encode regulators of apoptosis and proliferation.

Biological Activity I Assay Protocols (From Reference)
Targets
CDK9- Cyclin T1 (IC50 = 44 nM); cdk2-cyclin A (IC50 = 2441 nM); cdk1-cyclin B1 (IC50 = 5513 nM); cdk4-cyclin D1 (IC50 = 9242 nM); GSK3A (IC50 = 1460 nM); HGK/MAP4K4 (IC50 = 820 nM); ABL2/ARG (IC50 = 3640 nM)
ln Vitro

LDC000067 is more selective for CDK9 than other CDKs, even more so than flavopiridol and DRB, which are recognized inhibitors of CDK9. In comparison to CDK2/1/4/6/7, LDC000067 showed 55/125/210/ >227/ >227-fold selectivity for CDK9. LDC000067 inhibits transcription in vitro in a dose-dependent and ATP-competitive manner. Gene expression profiling of LDC000067-treated cells shows a selective reduction of short-lived mRNAs, such as significant regulators of apoptosis and proliferation[1].

ln Vivo

Enzyme Assay
The LANCE Ultra KinaSelect Ser/Thr kit, which uses fluorescence resonance energy transfer (FRET) to calculate IC50 values, is used to measure the effectiveness of different CDK inhibitors. In summary, a CDK-cyclin pair phosphorylates a particular ULight MBP peptide substrate (final concentration of 50 nM) in a buffer containing ATP at the concentration of the Km values of each individual kinase (50 mM HEPES-KOH pH 7.5, 10 mM MgCl2, 1 mM EGTA, and 2 mM dithiothreitol) for one hour at room temperature. Phosphorylation is then identified by adding particular anti-phospho-antibodies (2 nM) labeled with Eu; these antibodies bind to the phosphopeptide and produce a FRET signal. After that, FRET signals are recorded[1].
Cell Assay
Specifically, LDC000067 exhibits selectivity for CDK9 over other CDKs ranging from 55-fold to over 230-fold, with an IC50 value of 44(10 nM). Its ATP-competitive kinase binding assay further demonstrates this selectivity. Apoptosis and the tumour suppressor protein p53 are two additional effects of LDC000067 on whole cells. Furthermore, gene expression profiling of cells treated with LDC000067 reveals a selective reduction of short-lived mRNAs, such as MCL1 and MYC, which encode regulators of proliferation and apoptosis.
Animal Protocol


References

[1]. 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.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C18H18N4O3S
Molecular Weight
370.43
Exact Mass
370.11
Elemental Analysis
C, 58.36; H, 4.90; N, 15.13; O, 12.96; S, 8.65
CAS #
1073485-20-7
Appearance
Solid powder
SMILES
COC1=CC=CC=C1C2=CC(=NC=N2)NC3=CC=CC(=C3)CS(=O)(=O)N
InChi Key
GGQCIOOSELPMBB-UHFFFAOYSA-N
InChi Code
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)
Chemical Name
[3-[[6-(2-methoxyphenyl)pyrimidin-4-yl]amino]phenyl]methanesulfonamide
Synonyms
LDC067; LDC000067; LDC-000067; LDC-067; LDC 067; LDC 000067
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: ~74 mg/mL (~199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.6996 mL 13.4978 mL 26.9957 mL
5 mM 0.5399 mL 2.6996 mL 5.3991 mL
10 mM 0.2700 mL 1.3498 mL 2.6996 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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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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.
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Biological Data
  • LDC000067

    Inhibition ofin vitrotranscription by LDC067.2014 Jan;171(1):55-68.

  • LDC000067

    Microarray analysis of THP1 cells treated with LDC067.2014 Jan;171(1):55-68.

  • LDC000067

    Increase of RNAPII pausing atMYCin the presence of LDC067.

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