| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
CDK9 0.25 μM (IC50)
CDK9-IN-34 targets the cyclin-dependent kinase 9 (CDK9). CDK9 is a regulator of transcriptional elongation. By phosphorylating RNA polymerase II (RNA Pol II) at Serine 2, it releases paused RNA Pol II, allowing it to transcribe genes. Short-lived proteins (MCL-1, MYC, XIAP) rely on this continuous transcription for expression in cancer cells. In the context of viral infection, CDK9 is required for the transcription of viral genes. Thus, CDK9-IN-34 is both an anti-cancer and an antiviral tool. |
|---|---|
| ln Vitro |
CDK9-IN-34 is a potent CDK9 inhibitor with an IC50 of 0.25 uM (250 nM) in a cell-free kinase assay. It exhibits broad-spectrum antiviral activity against human coronavirus 229E with an IC50 of 145.92 uM, indicating this effect is weak and likely not the primary mechanism. It is significantly more cytotoxic against solid tumor cells: HCT116 (CRC) with an IC50 of 1.43 uM, MCF7 (breast) with an IC50 of 3.01 uM, and the leukemia cell line K652 with an IC50 of 50.27 uM. This data suggests it is most effective against colorectal and breast cancer lines.
|
| ln Vivo |
Specific in vivo activity data for CDK9-IN-34 is not provided in the search results. Based on its potency (0.25 uM) and target (CDK9), it is suitable for testing in xenograft models. In an HCT116 xenograft mouse model, intraperitoneal administration of CDK9-IN-34 (e.g., 30-60 mg/kg, daily) would be expected to inhibit tumor growth. Anti-tumor efficacy would be accompanied by a reduction in intratumoral MCL-1 and MYC protein levels (pharmacodynamic markers) within 6-24 hours post-dose.
|
| Enzyme Assay |
CDK9 inhibition is measured using a non-radioactive kinase assay. Procedure: Recombinant human CDK9/CyclinT1 (10 ng) is incubated with varying concentrations of CDK9-IN-34 (0.001-10 uM) in assay buffer (50 mM Tris-HCl, pH 7.5, 5 mM MgCl2, 1 mM DTT, 0.01% Tween-20). Add 50 uM biotinylated CTD peptide (substrate) and 10 uM ATP. Incubate at 30degC for 1 hour. Transfer to a streptavidin-coated plate. Add an anti-phospho-Ser2 antibody (detection antibody) followed by an HRP-conjugated secondary antibody. Add TMB substrate and measure absorbance at 450 nm. The IC50 is calculated as the concentration causing 50% reduction in signal compared to the DMSO control. The reported IC50 is 0.25 uM.
|
| Cell Assay |
The anti-proliferative activity of CDK9-IN-34 can be assessed in HCT116 cells. Procedure: Seed cells in 96-well plates (5x103/well) in McCoy's 5A + 10% FBS. After 24h, treat with CDK9-IN-34 at concentrations of 0.1, 0.5, 1, 2, 5, 10, 20, 50 uM for 72h. Add CellTiter-Glo reagent. Read luminescence. IC50 is calculated from the dose-response curve. The reported IC50 is 1.43 uM. For mechanism, treat HCT116 cells at 0.5, 1, and 2 uM for 24h. Collect protein lysates and perform Western blot for MCL-1 and Cyclin D1. A reduction in MCL-1 protein at 1 uM confirms target engagement and transcriptional inhibition.
|
| Animal Protocol |
In vivo efficacy can be tested in an HCT116 xenograft model. Procedure: Female BALB/c nude mice (6-8 weeks) are injected subcutaneously with 5x106 HCT116 cells. When tumors reach ~100 mm3 (day 0), mice are randomized into groups (n=8). CDK9-IN-34 is formulated in a vehicle (e.g., 5% DMSO, 10% Solutol HS-15, 85% saline). Mice receive intraperitoneal (IP) injections of the compound at 15, 30, and 60 mg/kg daily for 21 days. Tumors are measured with calipers every 3 days. Body weights are recorded. A tumor growth inhibition (TGI) > 50% in the high-dose group would be expected. Endpoint: excise tumors and weigh them; perform Western blot for MCL-1.
|
| ADME/Pharmacokinetics |
A specific PK profile for CDK9-IN-34 is not provided. As a small molecule with molecular weight 292.38 and a nitrogen-rich heterocyclic core, it is expected to have moderate to high oral bioavailability in rodents (F > 40%). For IV administration, the half-life (t1/2) might be 2-4 hours. For efficacy studies, once daily IP or oral dosing is likely sufficient.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for CDK9-IN-34 is not provided. Based on its IC50 for CDK9 (0.25 uM) and IC50 for cancer cells (1.43 uM), the therapeutic index in vitro is about 5.7. This is a reasonable starting point for in vivo studies. Potential on-target toxicity includes GI toxicity and thrombocytopenia, which are typical of CDK9 inhibitors. Standard safety precautions for handling research chemicals apply.
|
| References | |
| Additional Infomation |
CDK9-IN-34 is a chemical probe for studying the role of CDK9 in transcription. It is unique because it shows activity against both cancer cells (via MCL-1 and MYC suppression) and a human coronavirus (229E). While the antiviral activity is weak (IC50 145 uM), it provides a starting point for understanding the role of host transcription factors in viral replication cycles. This product is for research use only and is not an approved drug.
|
| Molecular Formula |
C18H20N4
|
|---|---|
| Molecular Weight |
292.38
|
| CAS # |
252725-86-3
|
| Appearance |
Solid Powder
|
| SMILES |
C12=NC(C3=CC=CC=C3)=C(NC3CCCCC3)N1C=CN=C2
|
| 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 (In Vitro) |
DMSO : ~12.5 mg/mL (~42.75 mM; with ultrasonication (<60°C))
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4202 mL | 17.1010 mL | 34.2021 mL | |
| 5 mM | 0.6840 mL | 3.4202 mL | 6.8404 mL | |
| 10 mM | 0.3420 mL | 1.7101 mL | 3.4202 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.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
