| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4). By inhibiting MAP4K4 activity, the compound modulates downstream signaling pathways such as JNK and NF-κB, which are involved in cell survival, motility, and inflammatory responses.
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| ln Vitro |
MAP4K4 is a serine/threonine protein inhibitor that antidiabetic medications may find useful to target [1].
In kinase assay, MAP4K4-IN-3 demonstrates potent inhibitory activity with an IC50 of 14.9 nM. In cell-based assays, the compound shows an IC50 of 470 nM. The compound exhibits a selectivity profile that supports its use in dissecting MAP4K4-dependent signaling networks. |
| ln Vivo |
Compound 2 (MAP4K4-IN-3; 25 mg/kg, dose) has a 5-day telemetry stability. There are numerous unfavorable drug responses. During the trial, there was a significant reduction in sleep and weight (7%) as compared to the controls. Treatment with MAP4K4-IN-3 increased maximal heart rate by 25 bpm for cardiovascular endpoints [2].
Oral dosing in telemetered rats for 5 days with MAP4K4-IN-3 at 25 mg/kg twice daily results in several adverse effects, including substantial weight loss of approximately 7% and body temperature increases of 0.4°C relative to controls. Maximal heart rate increases of 25 beats per minute are also induced by treatment. |
| Enzyme Assay |
Kinase activity assays are performed to determine the IC50 value against MAP4K4. Recombinant MAP4K4 enzyme is incubated with varying concentrations of the compound and a peptide substrate in the presence of ATP. The phosphorylation level of the substrate is measured, and the IC50 is calculated from the dose-response curve.
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| Cell Assay |
Cellular assays are conducted to evaluate the inhibitory effect of MAP4K4-IN-3 in cell-based systems. Cells are treated with varying concentrations of the compound, and the inhibition of MAP4K4-mediated cellular signaling is assessed. The cellular IC50 is determined to be 470 nM.
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| Animal Protocol |
In vivo studies are performed in telemetered rats to assess the pharmacological effects and safety profile. The compound is administered orally at 25 mg/kg twice daily for 5 days. Body weight, body temperature, and cardiovascular parameters including heart rate are monitored throughout the study.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of MAP4K4-IN-3 have not been extensively reported in the available literature. As a small molecule kinase inhibitor, the compound is expected to be amenable to oral administration based on the in vivo studies conducted in rats. Further PK characterization would be required for comprehensive profiling.
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| Toxicity/Toxicokinetics |
In telemetered rats, oral administration of MAP4K4-IN-3 at 25 mg/kg twice daily for 5 days results in mechanism-based safety concerns, including substantial weight loss (~7%), body temperature increases (0.4°C), and heart rate increases (up to 25 bpm). These findings suggest potential on-target or off-target toxicities that warrant further investigation.
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| References |
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| Additional Infomation |
MAP4K4-IN-3 is primarily a research tool for studying MAP4K4 biology and evaluating the therapeutic potential of MAP4K4 inhibition in diabetes and metabolic disorders. The compound is not approved for clinical use and is intended for research purposes only. Further studies are needed to fully elucidate its therapeutic potential and safety profile.
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| Molecular Formula |
C15H12CLN5
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|---|---|
| Molecular Weight |
297.742280960083
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| Exact Mass |
297.078
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| CAS # |
1811510-58-3
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| PubChem CID |
127036775
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.3
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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 |
2
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| Heavy Atom Count |
21
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| Complexity |
326
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)C1C(N)=NC=C(C2=CN=C(N)N=C2)C=1
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| InChi Key |
KSQDIECZAQKQQW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H12ClN5/c16-12-3-1-9(2-4-12)13-5-10(6-19-14(13)17)11-7-20-15(18)21-8-11/h1-8H,(H2,17,19)(H2,18,20,21)
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| Chemical Name |
5-[6-amino-5-(4-chlorophenyl)pyridin-3-yl]pyrimidin-2-amine
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| Synonyms |
MAP4K4IN3; MAP4K4 IN 3
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~10 mg/mL (~33.59 mM)
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| 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 | 3.3586 mL | 16.7932 mL | 33.5864 mL | |
| 5 mM | 0.6717 mL | 3.3586 mL | 6.7173 mL | |
| 10 mM | 0.3359 mL | 1.6793 mL | 3.3586 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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