| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
The primary targets of FMF-04-159-2 are cyclin-dependent kinases, specifically CDK14 (also known as PFTK1) and CDK16 (also known as PCTAIRE1). It also inhibits CDK2 with lower potency. As a covalent inhibitor, FMF-04-159-2 forms a covalent bond with its target kinases, leading to irreversible inhibition. By inhibiting CDK14 and CDK16, the compound modulates cell cycle progression, neuronal function, and signaling pathways such as Wnt/beta-catenin. Its ability to reduce alpha-synuclein aggregation in neurons highlights its potential in neurodegenerative disease research. The compound's selectivity for CDK14 and CDK16 over other kinases is a key feature of its mechanism.
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| ln Vitro |
HCT116 proliferation is inhibited by FMF-04-159-2, with an IC50 of 1,144±190 nM[1].
In vitro, FMF-04-159-2 is a potent inhibitor of CDK14 and CDK16. It inhibits CDK14 with an IC50 of 39.6 nM in cellular BRET assays and CDK16 with an IC50 of 10 nM in kinase activity inhibition assays. It also inhibits CDK2 with an IC50 of 256 nM. The compound reduces alpha-synuclein aggregation in neurons and attenuates the progression and metastasis of triple-negative breast cancer (TNBC) by weakening Wnt/beta-catenin signaling. Its potent and selective inhibition of CDK14 and CDK16 makes it a valuable tool for studying the role of these kinases in various cellular processes and diseases. |
| ln Vivo |
In vivo, FMF-04-159-2 has been shown to be effective in Parkinson's disease models by reducing alpha-synuclein aggregation in neurons. It also attenuates the progression and metastasis of triple-negative breast cancer (TNBC) by weakening Wnt/beta-catenin signaling. These in vivo effects highlight the compound's potential as a therapeutic agent for neurodegenerative diseases and cancer. Further studies are needed to evaluate its pharmacokinetics, toxicity, and efficacy in animal models. The compound's ability to target CDK14 and CDK16 makes it a promising candidate for further development.
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| Enzyme Assay |
The in vitro kinase inhibition activity of FMF-04-159-2 can be assessed using cell-free kinase assays with recombinant CDK14, CDK16, or CDK2 enzymes. A typical protocol involves incubating the kinase with a peptide substrate, ATP, and FMF-04-159-2 at various concentrations in a kinase buffer. The reaction is carried out at 30degC for 30-60 minutes. The amount of phosphorylated substrate is measured using a kinase activity assay kit, such as a luminescent ATP detection assay or a radioactive filter-binding assay. The IC50 value is determined by plotting the percentage of kinase activity remaining against the compound concentration. The selectivity of the compound can be assessed by testing its activity against a panel of related kinases.
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| Cell Assay |
For in vitro cellular experiments, cells (e.g., neurons, cancer cell lines) are cultured in appropriate media and treated with FMF-04-159-2 at various concentrations (typically 0.1-100 microM). After treatment, cells are harvested, and various endpoints are measured. For studies on alpha-synuclein aggregation, cells expressing alpha-synuclein are treated with the compound, and aggregation is assessed by immunostaining or biochemical assays. For studies on TNBC, cell proliferation, migration, and invasion are assessed using MTT, wound healing, and Transwell assays. Wnt/beta-catenin signaling is assessed by measuring the expression of target genes (e.g., Axin2, c-Myc) by qRT-PCR.
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| Animal Protocol |
In vivo animal experiments with FMF-04-159-2 would typically involve oral or intraperitoneal administration in mouse models of Parkinson's disease or triple-negative breast cancer. For Parkinson's disease models, the compound is administered to alpha-synuclein transgenic mice, and motor function, alpha-synuclein aggregation, and neurodegeneration are assessed. For TNBC models, the compound is administered to tumor-bearing mice, and tumor growth, metastasis, and survival are monitored. Pharmacokinetic and toxicity studies are also performed to characterize its safety profile. Further preclinical studies are needed to fully evaluate its in vivo activity.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for FMF-04-159-2 are not well-documented in the available literature. As a small molecule inhibitor with a molecular weight of approximately 750 g/mol, it is expected to have moderate lipophilicity. Its pharmacokinetic properties, including oral bioavailability, half-life, and tissue distribution, would need to be characterized in preclinical studies to support its development as a therapeutic agent. The compound is typically stored at -20degC and is stable for up to 3 years.
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| Toxicity/Toxicokinetics |
The toxicity profile of FMF-04-159-2 has not been extensively characterized. As a covalent kinase inhibitor, potential toxicities may include off-target effects on other kinases and irreversible inhibition of essential cellular processes. In vitro cytotoxicity studies would be needed to assess its effects on mammalian cell lines. In vivo toxicity studies in animal models would also be required to determine its safety profile. The compound should be handled with standard laboratory precautions and is intended for research use only.
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| References | |
| Additional Infomation |
FMF-04-159-2 is a potent covalent inhibitor of CDK14 and CDK16. It inhibits CDK14 with an IC50 of 39.6 nM and CDK16 with an IC50 of 10 nM. It also inhibits CDK2 with an IC50 of 256 nM. FMF-04-159-2 reduces alpha-synuclein aggregation in neurons and attenuates the progression and metastasis of triple-negative breast cancer by weakening Wnt/beta-catenin signaling. The compound is a valuable tool for studying the role of CDK14 and CDK16 in neurodegenerative diseases and cancer. It is available as a research compound and is not approved for clinical use.
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| Molecular Formula |
C28H30CL3N7O5S
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|---|---|
| Molecular Weight |
683.005701541901
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| Exact Mass |
681.109
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| CAS # |
2364489-81-4
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| Related CAS # |
2364489-81-4;
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| PubChem CID |
138454780
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| Appearance |
White to off-white solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
44
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| Complexity |
1140
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C=C(C=1C(NC1C=NNC=1C(NC1CCN(CC1)S(C1C=CC=C(C=1)NC(/C=C/CN(C)C)=O)(=O)=O)=O)=O)Cl)Cl
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| InChi Key |
HZPYSAHDRSBARR-QPJJXVBHSA-N
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| InChi Code |
InChI=1S/C28H30Cl3N7O5S/c1-37(2)10-4-7-24(39)33-19-5-3-6-20(15-19)44(42,43)38-11-8-18(9-12-38)34-28(41)26-23(16-32-36-26)35-27(40)25-21(30)13-17(29)14-22(25)31/h3-7,13-16,18H,8-12H2,1-2H3,(H,32,36)(H,33,39)(H,34,41)(H,35,40)/b7-4+
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| Chemical Name |
(E)-N-(1-((3-(4-(dimethylamino)but-2-enamido)phenyl)sulfonyl)piperidin-4-yl)-4-(2,4,6-trichlorobenzamido)-1H-pyrazole-3-carboxamide
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| Synonyms |
FMF-04-159-2FMF 04-159-2FMF04-159-2FMF-04 159-2
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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 |
| 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 : ~250 mg/mL (~366.03 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.05 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 20.8 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: ≥ 2.08 mg/mL (3.05 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 20.8 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 | 1.4641 mL | 7.3205 mL | 14.6411 mL | |
| 5 mM | 0.2928 mL | 1.4641 mL | 2.9282 mL | |
| 10 mM | 0.1464 mL | 0.7321 mL | 1.4641 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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