DDD107498 is a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, targeting on PfeEF2 (P. falciparum translation elongation factor 2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. DDD107498 showed excellent activity against 3D7 parasites with EC50 value of 1nM. DDD107498 was more potent than artesunate in ex vivo assays against a range of clinical isolates of both P. falciparum with median EC50 value of 0.81nM and P. vivax with median EC50 value of 0.51nM. DDD107498 displayed excellent pharmacokinetic properties in preclinical species, including good oral bioavailability and long plasma half-life. DDD107498 was very active in several mouse models of malaria. It had a 90% reduction in parasitaemia (ED90) of 0.57mg/kg after a single oral dose in mice infected with the rodent parasite Plasmodium berghei. DDD107498 at concentration<1μM dose-dependently protein synthesis via eEF2, in the cytoplasm as opposed to the apicoplast, the site of action of tetracycline and azithromycin[3].
作用机制
DDD107498 targets protein synthesis via PfeEF2.[3]
Cabamiquine 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HepG2/C3A cells
3.58 nM(EC50)
24 h
To evaluate the inhibitory effect of Cabamiquine on hepatic stage Plasmodium infection. Results showed that Cabamiquine did not affect hepatocyte viability at tested concentrations and effectively inhibited Plasmodium growth.
ACS Infect Dis. 2025 Jan 10;11(1):69-79
Plasmodium falciparum clinical isolates
7.5 nM (15× EC50)
6 days
Evaluate the susceptibility of clinical isolates to Cabamiquine
Nat Commun. 2023 Aug 25;14(1):5205
Cabamiquine 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NMRI mice
P. berghei ANKA infection model
Oral
0.3 mg/kg, 0.6 mg/kg, 1.5 mg/kg
Single dose, monitored up to 37 days
To evaluate the preventive effect of Cabamiquine on hepatic stage Plasmodium infection in vivo. Results showed that Cabamiquine at 1.5 mg/kg completely prevented the appearance of blood stage parasites.
ACS Infect Dis. 2025 Jan 10;11(1):69-79
NOD/SCID/IL2rγnull (NSG) mice
Humanized mouse model
Oral
12 mg/kg
Single dose
Evaluate the antimalarial efficacy and resistance mutations of Cabamiquine in a mouse model
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