MMV693183
MMV693183 is an orally active inhibitor of Plasmodium falciparum acetyl-CoA synthetase (AcAS), with an IC50 of 300 nM against Plasmodium falciparum. MMV693183 exhibits potent inhibitory activity against clinical isolates of malaria parasites, including Artemisinin (HY-B0094)-resistant strains. MMV693183 is metabolized in vivo into the active antimetabolite CoA-MMV693183, which exerts effects of killing asexual blood-stage parasites and blocking transmission to Anopheles mosquitoes by binding to and inhibiting the function of acetyl-CoA synthetase, thereby reducing the levels of acetyl-CoA and 4'-phosphopantetheine. In humanized mouse models, MMV693183 shows favorable in vivo efficacy, drug-like properties, and no significant cytotoxicity or off-target activity against human cells. MMV693183 is widely used in malaria-related research as a parasiticide and metabolic disruptor.
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- CAS No.: 2446681-27-0
- 화학식: C16H21F3N2O4
- 분자량:362.34
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Biological Activity
MMV693183 potently inhibits the in vitro asexual blood-stage growth of Plasmodium falciparum strains with an IC50 of 2.1-2.8 nM; it also inhibits the in vitro growth/schizont maturation of clinical isolates of Plasmodium falciparum and P. vivax with low nanomolar activity[1].
MMV693183 inhibits the viability of Plasmodium falciparum NF54-HGL gametocytes, with an IC50 of 17.8-38.8 nM at 72 h. MMV693183 also potently inhibits female gametocyte activation (IC50=12 nM), but shows weak activity against male gametogenesis (IC50=1 μM)[1].
MMV693183 (1.5 nM, 500 nM; 72 h) renders AcAS conditional knockdown Plasmodium falciparum parasites 5-fold hypersensitive under AcAS knockdown conditions[1].
MMV693183 (10 μM) exhibits no in vitro cytotoxicity in human hepatocytes or HepG2 cells, and shows no significant off-target activity against human receptors, enzymes or channels at the concentration of 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Human hepatocytes or HepG2 cells
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Concentration:10 µM
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Incubation Time:72 h
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Result:Exhibited no in vitro cytotoxicity in human hepatocytes or HepG2 cells.
MMV693183 clears P. falciparum parasitemia to undetectable levels in humanized NSG mice within 4-6 days, with a modeled MIC of 3.2 ng/mL and MPC90 of 38.4 ng/mL[1].
MMV693183 (10-50 mg/kg; daily; 4 days) does not cause hemolytic toxicity in G6PD-A-deficient human erythrocyte-engrafted NSG mice[1].
MMV693183 (10-1000 mg/kg; p.o.; daily; 3-8 days) is well tolerated in Wistar Han rats at doses up to 1000 mg/kg for 3 days, with a >30-fold exposure safety margin at 30 mg/kg/day relative to predicted human efficacious exposure[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NSG (female, humanized with G6PD-A-deficient human erythrocytes to achieve >60% human erythrocytes)[1]
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Dosage:10 mg/kg; 25 mg/kg; 50 mg/kg
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Administration:daily; 4 days
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Result:Showed no signs of hemolytic toxicity; did not induce hemolysis of G6PD-A-deficient human erythrocytes.
Chemical Information
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CAS No. 2446681-27-0
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분자량 362.34
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화학식 C16H21F3N2O4
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SMILES
OCC(C)(C)[C@@H](O)C(NC[C@H](C)NC(C1=C(C=C(C(F)=C1)F)F)=O)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MMV693183 Related Classifications
HY-182685 Related Classifications
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