CDKI-73 (Synonyms: LS-007) |
| Catalog No.GC19096 |
CDKI-73 (LS-007) es un inhibidor de CDK9 muy eficaz y activo por vÍa oral, con valores de Ki de 4 nM, 4 nM y 3 nM para CDK9, CDK1 y CDK2, respectivamente.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1421693-22-2
Sample solution is provided at 25 µL, 10mM.
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CDKI-73 is a potent CDK9 inhibitor with Ki of 4 nM; shows selective toxicity to CLL cells(LD50=80 nM) versus normal B cell and normal CD34+ cell(LD50>20 uM).IC50 value: 4 nM/80 nM(Ki/LD50) [1]Target: CDK9 inhibitorin vitro: CDKI-73 was cytotoxic to all of the CLL samples tested (n = 38) with a mean LD50 value of 0.08uM ± 0.10 uM following exposure to drug for 48h. In contrast, normal B-lymphocytes (n = 10) and CD34+ normal bone marrow cells (n = 5) were significantly less susceptible to the cytotoxic effects of CDKI-73. Treatment of CLL cells with 0.1 uM CDKI-73 for 4h inhibited the phosphorylation of cdk9 and ser2 of RNA polymerase II. CDKI-73 induces a rapid loss of MCL1 protein and this is mediated by significant inhibition at the level of gene transcription. However, this inhibition is not restricted to MCL1 as similar reductions in XIAP and CCND2 were also observed following exposure to CDKI-73 for 4h [1]. CDKI-73 rapidly inhibited cellular CDK9 kinase activity and down-regulated the RNAPII phosphorylation. CDK9 shRNA was also found to down-regulate the Mnk1 expression. Both CDKI-73 and CDK9 shRNA decreased anti-apoptotic proteins Mcl-1 and Bcl-2 and induced apoptosis [2]. in vivo: CDKI-73 exhibited a favorable pharmacokinetic profile with oral bioavailability of F = 56% following a single intravenous bolus dose at 2 mg/kg and an oral dose at 10 mg/kg in mice [1].
References:
[1]. Xie S, et al. Antitumor action of CDK inhibitor LS-007 as a single agent and in combination with ABT-199 against human acute leukemia cells. Acta Pharmacol Sin. 2016 Nov;37(11):1481-1489.
[2]. Lam F, et al. Targeting RNA transcription and translation in ovarian cancer cells with pharmacological inhibitor CDKI-73. Oncotarget. 2014 Sep 15;5(17):7691-704.
| Cas No. | 1421693-22-2 | SDF | |
| Sinónimos | LS-007 | ||
| Canonical SMILES | CNC1=NC(C)=C(C2=C(F)C=NC(NC3=CC(S(=O)(N)=O)=CC=C3)=N2)S1 | ||
| Formula | C15H15FN6O2S2 | M.Wt | 394.45 |
| Solubility | DMSO : ≥ 52 mg/mL (131.83 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store 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 | 2.5352 mL | 12.6759 mL | 25.3518 mL |
| 5 mM | 0.507 mL | 2.5352 mL | 5.0704 mL |
| 10 mM | 0.2535 mL | 1.2676 mL | 2.5352 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)
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