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KDU691

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Chemical Structure| 1513879-19-0 同义名 : -
CAS号 : 1513879-19-0
货号 : A950283
分子式 : C22H18ClN5O2
纯度 : 99%+
分子量 : 419.864
MDL号 : MFCD28963927
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 145 mg/mL(345.35 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
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.