KDU691 是一种咪唑吡嗪类药物，对血阶段的裂殖体、配子体和肝期具有较强的抗寄生虫活性，它是PI4K抑制剂，选择性抑制双氢青蒿素预处理的恶性疟原虫。

KDU691 is a PI4K inhibitor.

KDU691 was evaluated for in vivo activity in rhesus macaques infected with P. cynomolgi sporozoites.?The prophylactically treated monkeys failed to become blood smear positive, while untreated control animals showed normal parasitemia development (primary parasitemia at day 8.9 p.i., with the first relapse within a month).?Thus, 5-day oral treatment with 20 mg/kg of KDU691 shortly after infection eradicated all liver-stage parasites, including hypnozoites.

Sporozoites were harvested from P. cynomolgi-infected mosquitoes, washed with phosphate-buffered saline (PBS), and diluted to 100,000 sporozoites (spz)/ml in PBS. One-milliliter aliquots of sporozoites were prepared and injected into monkeys via intravenous injection. During treatment, monkeys were weighed daily and received the compound via gavage, followed by gastric feeding. Monkeys in the prophylaxis groups were treated 20 min after the i.v. sporozoite injection. The other monkeys were treated when all the monkeys in the experiment (except those in the prophylaxis group) were blood-stage patent (at day 11 p.i.). To kill the blood-stage parasites, all monkeys received a 5-day treatment of 7.5 mg/kg of body weight of chloroquine (CQ), during compound dosing. KDU691 was formulated in 0.5% methylcellulose and 0.5% Tween 80 in water. LMV599 was formulated as a solid dispersion in a solution containing 5.6% (wt/wt) Tween 80 44.4% hydroxypropyl methylcellulose (HPMC) E3 38.9% Soluplus 11.1% vitamin E d-alphatocopheryl polyethylene glycol 1000 succinate.

1513879-19-0

C22H18ClN5O2

419.87

DMSO:150 mg/mL (357.26 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years