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| Targets |
MMV008138 targets IspD (2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase), an enzyme in the MEP (non-mevalonate) pathway of Plasmodium falciparum. The MEP pathway is essential for isoprenoid biosynthesis in the malaria parasite and is absent in humans, making it an attractive antimalarial target. MMV008138 is species-selective for PfIspD with an IC₅0 of 44 nM.
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| ln Vitro |
MMV008138 targets the Plasmodium falciparum MEP pathway's IspD enzyme[1]. Human IspD is not the target of MMV008138[1].
MMV008138 demonstrates potent in vitro antimalarial activity. It inhibits the growth of P. falciparum Dd2 strain with an IC₅0 of 250 nM. The compound shows species-selective inhibition of PfIspD with an IC₅0 of 44 nM. It is a selective antimalarial agent. Purity is typically >98%. |
| ln Vivo |
In vivo, MMV008138 is used as a research tool to study the MEP pathway and antimalarial drug development. Further in vivo studies in animal models of malaria would be required to fully characterize its therapeutic potential, efficacy, and pharmacokinetic properties. The compound is a promising lead for antimalarial drug development.
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| Enzyme Assay |
In vitro enzyme assays for MMV008138 typically employ recombinant PfIspD enzyme and measure its activity by monitoring the cytidylyltransferase reaction. Enzyme activity is assessed by coupling the reaction to a detection system (e.g., pyrophosphate detection) or by measuring substrate consumption. Inhibition is assessed by incubating varying concentrations of MMV008138 with the enzyme and substrates. IC₅0 values are determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for MMV008138 involve treating P. falciparum-infected erythrocytes with varying concentrations of the compound (typically 0.001-100 microM range) for 48-72 hours. Parasite growth is assessed by microscopy, flow cytometry, or metabolic activity assays (e.g., [3H]-hypoxanthine incorporation). IC₅0 values are determined from dose-response curves. Cytotoxicity against host cells is evaluated to assess selectivity.
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| Animal Protocol |
In vivo animal studies for MMV008138 would typically employ mouse models of malaria (e.g., P. berghei or P. falciparum-infected mice). Infected animals would be administered MMV008138 via appropriate routes at various doses. Efficacy would be assessed by measuring parasitemia, survival, and clinical signs. Pharmacodynamic studies would assess target engagement.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MMV008138 are characteristic of small molecule antimalarial agents. With a molecular weight of 361.22, the compound is a small molecule. PK parameters including half-life, Cmax, Tmax, and AUC would be determined via LC-MS/MS analysis following administration in appropriate animal models.
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| Toxicity/Toxicokinetics |
MMV008138 is a research-grade compound for laboratory use only. As with all research chemicals, standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. The compound is not intended for human therapeutic use. Comprehensive toxicology data is not publicly available.
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| References |
[1]. Ghavami M, et al. Biological Studies and Target Engagement of the 2- C-Methyl-d-Erythritol 4-Phosphate Cytidylyltransferase (IspD)-Targeting Antimalarial Agent (1 R,3 S)-MMV008138 and Analogs. ACS Infect Dis. 2018 Apr 13;4(4):549-559.
[2]. Yao ZK, et al. Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies. Bioorg Med Chem Lett. 2015 Apr 1;25(7):1515-9. |
| Additional Infomation |
MMV008138 (CAS# 1679333-73-3) is a species-selective antimalarial agent targeting PfIspD (IC₅0 = 44 nM). It inhibits the growth of P. falciparum Dd2 strain (IC₅0 = 250 nM). The compound is not approved for clinical use and is for research purposes only. It is typically stored at -20degC.
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| Molecular Formula |
C18H14CL2N2O2
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|---|---|
| Molecular Weight |
361.221962451935
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| Exact Mass |
360.043
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| CAS # |
1679333-73-3
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| PubChem CID |
987146
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
492
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1[C@H](N[C@@H](C2=C1C3=CC=CC=C3N2)C4=C(C=C(C=C4)Cl)Cl)C(=O)O
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| InChi Key |
ZJDRIKAAFJMYGX-JKSUJKDBSA-N
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| InChi Code |
InChI=1S/C18H14Cl2N2O2/c19-9-5-6-11(13(20)7-9)16-17-12(8-15(22-16)18(23)24)10-3-1-2-4-14(10)21-17/h1-7,15-16,21-22H,8H2,(H,23,24)/t15-,16+/m0/s1
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| Chemical Name |
(1R,3S)-1-(2,4-dichlorophenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid
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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 : ~125 mg/mL (~346.05 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.76 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 (5.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7684 mL | 13.8420 mL | 27.6840 mL | |
| 5 mM | 0.5537 mL | 2.7684 mL | 5.5368 mL | |
| 10 mM | 0.2768 mL | 1.3842 mL | 2.7684 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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