| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
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| Targets |
Manitimus targets dihydroorotate dehydrogenase (DHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway. DHODH catalyzes the conversion of dihydroorotate to orotate, which is a rate-limiting step in pyrimidine nucleotide synthesis. By inhibiting DHODH, Manitimus blocks pyrimidine synthesis, thereby inhibiting lymphocyte proliferation and exerting immunosuppressive effects. The compound's mechanism of action is similar to that of other DHODH inhibitors such as leflunomide and teriflunomide.
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| ln Vitro |
In vitro, Manitimus functions as an inhibitor of dihydroorotate dehydrogenase (DHODH). The compound exhibits immunosuppressive and antiproliferative activity. Manitimus is an experimental protein-protein interaction inhibitor that blocks the formation of specific tumor-related signaling protein complexes, thereby inhibiting downstream signaling and reducing tumor cell proliferation and survival. These in vitro properties make Manitimus a valuable tool for studying DHODH biology and immune function.
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| ln Vivo |
There were dose-related differential effects in rats treated with Manitimus: group 4 (Manitimus 5 mg/kg) had a mean survival of 15.7 days, while group 5 (Manitimus 10 mg/kg) had a mean survival of 19.1 days. Group 1's average survival duration was 25.4 days. 6 (50 mg/kg of manolimus) [1]. Comparing manitimus (15 mg/kg, p.o.) to control rats, the former resulted in a substantial decrease in neointimal area and percent stenosis, while the latter reduced the effects of CMV infection and increased intimal and medial cross-sectional area and medial wall thickness. graft [2].
In vivo, Manitimus has been studied in animal models for its immunosuppressive and antiproliferative effects. In Manitimus-treated rats, there is a dose-related, differential effect on survival: mean survival is 15.7 days at 5 mg/kg, 19.1 days at 10 mg/kg, and 25.4 days at 20 mg/kg. Manitimus (15 mg/kg, p.o.) results in significant effects in vivo. The compound prevents vascular remodeling after mechanical endothelial injury and has been studied for applications in transplant immunosuppression and autoimmune conditions. |
| Enzyme Assay |
Manitimus is not typically used in standard receptor binding assays. Its activity is assessed through DHODH enzyme inhibition assays or cell-based assays measuring lymphocyte proliferation. In enzyme inhibition assays, DHODH activity is measured by monitoring the conversion of dihydroorotate to orotate. Manitimus is incubated with the enzyme and substrate at varying concentrations, and product formation is quantified spectrophotometrically. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
Nonsecific activity is determined in control reactions without inhibitor. Cellular assays for Manitimus are performed using lymphocytes or other proliferating cells. Cells are cultured in appropriate media and treated with Manitimus at varying concentrations for defined time periods. Cell proliferation is assessed using standard assays such as [3H]-thymidine incorporation or BrdU incorporation. Cell viability is assessed using standard assays such as MTT or CellTiter-Glo. The compound's effects on pyrimidine synthesis may be assessed by measuring nucleotide levels.
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| Animal Protocol |
In vivo studies with Manitimus are conducted in animal models of transplantation, autoimmune disease, or cancer. Manitimus is administered via oral or intraperitoneal routes at defined doses and schedules. For transplantation studies, graft survival is monitored. For autoimmune studies, disease severity is assessed by clinical scoring and histology. For cancer studies, tumor growth is monitored. Pharmacokinetic parameters are determined from plasma samples collected at various time points. Manitimus has been studied in rat models with dose-related effects on survival.
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| ADME/Pharmacokinetics |
Manitimus has a molecular formula of C26H24N2O3 and a molecular weight of 412.48. The compound is an inhibitor of dihydroorotate dehydrogenase (DHODH). Detailed pharmacokinetic parameters, including oral bioavailability and half-life, have been characterized in preclinical studies. Manitimus contains an alkyne group and can undergo click chemistry reactions. The compound is soluble in DMSO. It should be stored at -20degC.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Manitimus are documented in preclinical studies. The compound is intended for research use only and is not approved for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines. The compound has a purity of ≥98%.
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| References |
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| Additional Infomation |
FK778 is a novel compound with multiple mechanisms of action. It has shown significant efficacy, good tolerability, and high safety in kidney transplant patients, and holds promise for a breakthrough in immunosuppressive therapy.
Drug Indications Investigations are underway for immunosuppression and transplant (rejection) treatment. Mechanism of Action FK778 exerts its immunosuppressive activity at the molecular level by inhibiting the de novo synthesis of pyrimidines. It inhibits the activity of dihydroorotate dehydrogenase (a key enzyme in this process), thereby inhibiting cell proliferation. Manitimus (FK778) is an inhibitor of dihydroorotate dehydrogenase (DHODH) and a potent immunosuppressive drug with immunosuppressive and antiproliferative activity. It prevents vascular remodeling after mechanical endothelial injury and can be used to study immune dysfunction. Manitimus has been studied for applications in cancer therapy, transplant immunosuppression, and autoimmune conditions. The compound is for research purposes only. |
| Molecular Formula |
CH4
|
|---|---|
| Molecular Weight |
16.0424604415894
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| Exact Mass |
308.077
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| CAS # |
202057-76-9
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| PubChem CID |
54686843
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
489.4±45.0 °C at 760 mmHg
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| Flash Point |
249.8±28.7 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.562
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| LogP |
3.49
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
540
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C#CCC/C(O)=C(C#N)/C(NC1=CC=C(C(F)(F)F)C=C1)=O
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| InChi Key |
IRELROQHIPLASX-SEYXRHQNSA-N
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| InChi Code |
InChI=1S/C15H11F3N2O2/c1-2-3-4-13(21)12(9-19)14(22)20-11-7-5-10(6-8-11)15(16,17)18/h1,5-8,21H,3-4H2,(H,20,22)/b13-12-
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| Chemical Name |
(Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]hept-2-en-6-ynamide
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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 (~811.00 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (20.28 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 62.5 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: ≥ 6.25 mg/mL (20.28 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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 | 62.3441 mL | 311.7207 mL | 623.4414 mL | |
| 5 mM | 12.4688 mL | 62.3441 mL | 124.6883 mL | |
| 10 mM | 6.2344 mL | 31.1721 mL | 62.3441 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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