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| Targets |
CMK primarily targets RSK2 (ribosomal S6 kinase 2), a serine/threonine kinase involved in the MAPK signaling pathway. The compound acts as an irreversible inhibitor of the CTD of RSK2, showing similar potency to the related inhibitor FMK. CMK also potently inhibits a Fyn mutant in which Val285 is replaced with Cys, with an IC₅0 of 1 nM. Additionally, CMK inhibits the growth of Cdc5 (L158G) with an IC₅0 of 36 nM, demonstrating significant selectivity over wild type Cdc5 (>30 microM). The compound has been reported to target hrr25, a thr4 kinase involved in transcription termination of specific classes of noncoding snoRNA genes.
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| ln Vitro |
CMK inhibits Cdc5 (L158G) growth with an IC50 value of 36 nM, which is higher than the wild type Cdc5 IC50 of 30 μM. In the cdc5-as1 strain, CMK exhibits a concentration-dependent first cell cycle mitotic arrest with an IC50 of 1.1 μM. Anaphase I of the first cell cycle is arrested, and anaphase spindle migration is delayed as a result of CMK inhibition of Cdc5 (L158G)[1].
CMK demonstrates potent in vitro inhibitory activity against RSK2 kinase. The compound inhibits the growth of Cdc5 (L158G) with an IC₅0 of 36 nM, which is significantly more effective than its action on wild type Cdc5 (>30 microM). CMK also potently inhibits a Fyn mutant in which Val285 was replaced with Cys, with an IC₅0 of 1 nM. In cell-based assays, CMK causes a concentration-dependent first cell cycle mitotic arrest in the cdc5-as1 strain with an IC₅0 of 1.1 microM, and leads to anaphase arrest and delay in anaphase spindle migration. The compound shows similar potency to FMK but exhibits less chemical stability. |
| ln Vivo |
In vivo activity data for CMK are limited, as the compound is primarily used in cell-based and biochemical research applications. Based on its mechanism as an irreversible RSK2 kinase inhibitor, potential in vivo studies would evaluate its effects on RSK2-mediated signaling pathways, cell proliferation, and tumor growth in animal models. The compound has been formulated for in vivo administration using 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline at 3.3 mg/mL. However, comprehensive pharmacokinetic and pharmacodynamic studies in animal models have not been extensively reported. The compound is intended for research purposes only and has not been evaluated in clinical trials for therapeutic applications.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for CMK typically involves measuring its inhibitory activity against RSK2 kinase using kinase activity assays. The assay system includes purified RSK2 enzyme, a suitable peptide substrate, and ATP, with reaction progress monitored by measuring phosphorylation of the substrate using radiolabeled ATP (32P-ATP) or through luminescence-based detection methods. CMK is added at varying concentrations to determine IC₅0 values. The compound is pre-incubated with the enzyme to allow for irreversible binding before the addition of substrate and ATP. Assay buffer typically contains HEPES, magnesium chloride, sodium chloride, and DTT at physiological pH. Reactions are incubated at 30degC and terminated by addition of phosphoric acid or EDTA, followed by detection of phosphorylated product.
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| Cell Assay |
The in vitro cell-based assay for CMK involves culturing relevant cell lines (e.g., mammalian cells expressing RSK2 or mutant Cdc5 strains) and treating them with varying concentrations of the compound. Cells are typically seeded in multi-well plates and incubated for 24-72 hours in appropriate growth media at 37degC with 5% CO2. Following treatment, cell viability is assessed using standard assays such as MTT, CCK-8, or CellTiter-Glo to determine IC₅0 values. For cell cycle analysis, cells are fixed, stained with propidium iodide, and analyzed by flow cytometry to assess mitotic arrest and anaphase progression. The compound's effects on RSK2-mediated signaling can be evaluated by Western blot analysis of downstream phosphorylation targets. CMK is soluble in DMSO at 150 mg/mL.
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| Animal Protocol |
In vivo animal studies for CMK have not been extensively documented in the literature. Based on the compound's mechanism as an RSK2 kinase inhibitor, potential animal studies would typically involve administration of the compound via intraperitoneal, intravenous, or oral routes in rodent models. A suggested in vivo formulation uses 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline at a concentration of 3.3 mg/mL. Dosing would be determined based on preliminary pharmacokinetic data and solubility profiles. Common endpoints in such studies would include evaluation of RSK2 inhibition in target tissues, assessment of tumor growth inhibition in xenograft models, and monitoring of general toxicity parameters. However, comprehensive in vivo efficacy and toxicity studies have not been widely reported for this compound.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of CMK have not been fully characterized in the literature. Based on its physicochemical properties, the compound has a molecular weight of 358.82 g/mol and a molecular formula of C1₈H1₉ClN4O2. CMK shows good solubility in DMSO (150 mg/mL, 418.04 mM) and has been formulated for in vivo studies using 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. The compound has a predicted relative density of 1.39 g/cm3. For storage, CMK powder can be kept at -20degC for 3 years, and in solution at -80degC for 1 year. The compound exhibits less chemical stability compared with FMK.
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| Toxicity/Toxicokinetics |
Toxicity data for CMK are limited, as the compound is a research-use kinase inhibitor and has not undergone extensive toxicological characterization. Standard safety precautions should be followed when handling this compound, including the use of appropriate personal protective equipment such as gloves and lab coats to prevent skin contact and inhalation. The compound should be handled in a well-ventilated area or fume hood. In case of accidental exposure, rinse affected areas with plenty of water and seek medical attention if irritation persists. Proper waste disposal procedures should be observed in accordance with local regulations. As with all research chemicals, exposure should be minimized and the compound should be stored securely away from incompatible materials.
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| References | |
| Additional Infomation |
CMK (CAS#: 821794-90-5) is a research-grade RSK2 kinase inhibitor with a molecular formula of C1₈H1₉ClN4O2 and a molecular weight of 358.82. Also known as 1-[4-Amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-2-chloroethanone, CMK acts as an irreversible inhibitor of the CTD of RSK2 with similar potency to FMK but lower chemical stability. The compound inhibits the growth of Cdc5 (L158G) with an IC₅0 of 36 nM and causes concentration-dependent mitotic arrest. CMK also potently inhibits a Fyn mutant (IC₅0 = 1 nM). The compound is soluble in DMSO at 150 mg/mL and is intended for research purposes only. No clinical trials or regulatory approvals have been reported for this compound.
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| Molecular Formula |
C18H19CLN4O2
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| Molecular Weight |
358.82206
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| Exact Mass |
358.119
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| Elemental Analysis |
C, 60.25; H, 5.34; Cl, 9.88; N, 15.61; O, 8.92
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| CAS # |
821794-90-5
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| Related CAS # |
FMK;821794-92-7;FMK-MEA;1414811-15-6
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| PubChem CID |
16663089
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
647.5±55.0 °C at 760 mmHg
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| Flash Point |
345.4±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.670
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| LogP |
1.55
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
458
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CCl)C1N(CCCO)C2C(=C(N)N=CN=2)C=1C1C=CC(C)=CC=1
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| InChi Key |
PELFTNQHGSITLB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H19ClN4O2/c1-11-3-5-12(6-4-11)14-15-17(20)21-10-22-18(15)23(7-2-8-24)16(14)13(25)9-19/h3-6,10,24H,2,7-9H2,1H3,(H2,20,21,22)
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| Chemical Name |
1-[4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-6-yl]-2-chloroethanone
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| Synonyms |
821794-90-5
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~150 mg/mL (~418.0 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7869 mL | 13.9346 mL | 27.8691 mL | |
| 5 mM | 0.5574 mL | 2.7869 mL | 5.5738 mL | |
| 10 mM | 0.2787 mL | 1.3935 mL | 2.7869 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.
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