BiochemProbe — Life Science Research Reagents

DSM705 free base · Synonyms: DSM-705 · DSM 705

DSM705 is a pyrrole-based Dihydroorotate Dehydrogenase inhibitor.

For research use only. Not for human or veterinary use.

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DSM705 structure

CAS No.: 2653225-38-6

Download structure (.mol)

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Description

DSM705 is a pyrrole-based Dihydroorotate Dehydrogenase (DHODH) inhibitor. DSM705 exhibits nanomolar potency against Plasmodium DHODH and Plasmodium parasites, with no inhibition of mammalian DHODHs. DSM705 is a potent antimalarial compound.

Biological activity

In Vitro DSM705 shows inhibitory activity against P. falciparum DHODH (PfDHODH, IC50=95 nM), P. vivax DHODH (PvDHODH, IC50=52 nM) and Pf3D7 cells (EC50=12 nM), with no inhibition of the human enzyme. In Vivo DSM705 (3-200 mg/kg; p.o. twice a day for 6 days) provides the maximum rate of parasite killing at the dose of 50 mg/kg and fully suppresses parasitemia by days 7-8. DSM705 (2.6 and 24 mg/kg; a single p.o.) exhibits high oral bioavailability (74%, 70%), apparent t1/2 (3.4, 4.5 h) and Cmax (2.6, 20 μM) in Swiss outbred mice. DSM705 (2.3 mg/kg; a single i.v.) exhibits plasma clearance (CL=2.8 mL/min/kg) and Vss (1.3 L/kg) in mice.

Identifiers

SMILES
C[C@H](C1=NC=NN1)NC(C2=C(C(C3(C4=CC=C(N=C4)C(F)(F)F)CC3)=CN2)C)=O
InChIKey
JUBPRXDFKLPILK-LLVKDONJSA-N

Specifications

MW (average)
404.3890
Formula
C19H19F3N6O
CAS No.
2653225-38-6
Physical state
Other
Color
other
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage
Powder -20℃ 2 years; In solvent -20℃ 1 month;

Solubility

Soluble in DMSO

References

[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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