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DSM705

Catalog No. T40291 CAS 2653225-38-6

Synonyms: DSM705

DSM705 is a pyrrole-based inhibitor of Dihydroorotate Dehydrogenase (DHODH). It demonstrates high potency in the nanomolar range against Plasmodium DHODH and Plasmodium parasites, while not interfering with mammalian DHODHs. DSM705 shows significant efficacy as an antimalarial compound.

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DSM705, CAS 2653225-38-6

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Biological Description

Chemical Properties

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Description	DSM705 is a pyrrole-based inhibitor of Dihydroorotate Dehydrogenase (DHODH). It demonstrates high potency in the nanomolar range against Plasmodium DHODH and Plasmodium parasites, while not interfering with mammalian DHODHs. DSM705 shows significant efficacy as an antimalarial compound.
Targets&IC50	DHODH (P. vivax):52 nM (IC50), DHODH (P. falciparum):95 nM (IC50)
In vitro	DSM705 exhibits inhibitory activity against both P. falciparum DHODH (Pf DHODH, IC50=95 nM) and P. vivax DHODH (Pv DHODH, IC50=52 nM), as well as Pf 3D7 cells (EC50=12 nM), without inhibiting the human counterpart of the enzyme[1].
In vivo	DSM705, when administered orally at doses ranging from 3-200 mg/kg twice daily for 6 days, achieves optimal parasite eradication at a 50 mg/kg dosage, completely eliminating parasitemia by the 7th or 8th day. In Swiss outbred mice, a single oral dose of DSM705 at 2.6 and 24 mg/kg demonstrates high oral bioavailability (74%, 70%), extended half-life (3.4, 4.5 hours), and peak concentration (C max) values of 2.6 and 20 μM, respectively. Furthermore, a single intravenous dose of 2.3 mg/kg in mice results in a clearance rate (CL) of 2.8 mL/min/kg and a steady-state volume of distribution (V ss) of 1.3 L/kg. The efficacy of DSM705 was tested in SCID mice inoculated with parasites, with oral doses (p.o.) administered twice daily for 6 days across varying concentrations (3, 10, 20, 50, 100, 200 mg/kg), demonstrating dose-dependent parasite eradication and complete suppression of parasitemia by days 7-8. Similarly, pharmacokinetic analysis in Swiss Outbred Mice with doses of 2.6 and 24 mg/kg for oral administration and 2.3 mg/kg for intravenous (i.v.) administration showed notable outcomes in bioavailability, half-life, concentration maxima, clearance, and distribution volume.

Synonyms	DSM705
Molecular Weight	404.397
Formula	C19H19F3N6O
CAS No.	2653225-38-6

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

References and Literature

1. Palmer MJ, et, al. Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series. J Med Chem. 2021 May 13;64(9):6085-6136.

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO (Master liquid 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 master liquid, next add μL PEG300， mix and clarify, next add μL Tween 80，mix and clarify, next add μL ddH₂O, mix and clarify.

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Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

DSM705 2653225-38-6 DSM 705 DSM-705 inhibitor inhibit

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