同义名 :	-
	CAS号 :	1513879-19-0
	货号 :	A950283
	分子式 :	C22H18ClN5O2
	纯度 :	99%+
	分子量 :	419.86
	MDL号 :	MFCD28963927
	存储条件：	Pure form Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

Phosphatidylinositol 4-kinases (PI4K) are enzymes responsible for the production of phosphatidylinositol 4-phosphates, important intermediates in several cell signaling pathways. PI4KIIα is the most abundant membrane-associated kinase in mammalian cells and is involved in a variety of essential cellular functions[3]. Phosphatidylinositol 4-kinases (PI4Ks) and small guanosine triphosphatases (GTPases) are essential for processes that require expansion and remodeling of phosphatidylinositol 4-phosphate (PI4P)-containing membranes, including cytokinesis, intracellular development of malarial pathogens, and replication of a wide range of RNA viruses[4]. KDU691, an imidazopyrazine with potent anti-parasitic activity against blood stage schizonts, gametocytes and liver stages, is a Plasmodium PI4K inhibitor. KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites (IC50=1.5nM)[5]. KDU691 is selective for P. vivax PI4K over recombinant human PI4KβIII and PI3Kα, -β, -ɣ, and -δ (IC50s = 7.9, 8.8, 2.4, 8, and 3.4 µM, respectively), as well as VPS34 (IC50 = >9.7 µM) and 36 additional kinases in a panel of lipid and protein kinases (IC50s = >10 µM)[6]. During the 5 days of dosing, the animals that are treated with KDU691 show a transient yellow skin color since the fourth day. The KDU691 radical-cure group (group 691-RC) becomes blood-stage positive again at 31.8 days p.i. (range, 31 to 32 days). Clinical chemistry analysis of the group 691-RC monkeys reveals that bilirubin levels accumulate during the 5-day radical-cure treatment with KDU691[7].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.38mL 0.48mL 0.24mL	11.91mL 2.38mL 1.19mL	23.82mL 4.76mL 2.38mL

参考文献

[1]Dembele L, Ang X, et al. The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites. Sci Rep. 2017 May 24;7(1):2325. [2]Zeeman AM, Lakshminarayana SB, et al. PI4 Kinase Is a Prophylactic but Not Radical Curative Target in Plasmodium vivax-Type Malaria Parasites. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2858-63. [3]Avanti Gokhale,et al. Identification of the Interactome of a Palmitoylated Membrane Protein, Phosphatidylinositol 4-Kinase Type II Alpha. Methods Mol Biol. 2016. 1376, 35-42. [4]John E Burke,et al. Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors. Science. 2014. 344(6187),1035-8. [5]Dembele L, et al. The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites. Sci Rep. 2017. 7(1), 2325. [6]Zou, B., Nagle, A., Chatterjee, A.K., et al. Lead optimization of imidazopyrazines: a new class of antimalarial with activity on Plasmodium liver stages. ACS Med. Chem. Lett. 2014. 5(8), 947-950. [7]Zeeman AM, et al. PI4 Kinase Is a Prophylactic but Not Radical Curative Target in Plasmodium vivax-Type Malaria Parasites. Antimicrob Agents Chemother. 2016. 60(5), 2858-2863.