ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors KDU691

KDU691

Product NameKDU691
CAS1513879-19-0
MFC22H18ClN5O2
MW419.86
EINECS
MOL File1513879-19-0.mol

Chemical Properties

Density	1.35±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO:PBS (pH 7.2) (1:9):0.1(Max Conc. mg/mL);0.24(Max Conc. mM) Ethanol:10.0(Max Conc. mg/mL);23.82(Max Conc. mM)
form	A crystalline solid
pka	14.59±0.46(Predicted)
color	White to off-white
InChI	1S/C22H18ClN5O2/c1-24-21(29)15-5-3-14(4-6-15)19-11-26-20-12-25-18(13-28(19)20)22(30)27(2)17-9-7-16(23)8-10-17/h3-13H,1-2H3,(H,24,29)
InChIKey	TYMFFISSODJRDV-UHFFFAOYSA-N
SMILES	O=C(N(C1=CC=C(Cl)C=C1)C)C(N=C2)=CN3C2=NC=C3C4=CC=C(C(NC)=O)C=C4

Safety Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids

Usage And Synthesis

Description

KDU691 is an antimalarial compound. It inhibits recombinant P. vivax phosphatidylinositol 4-kinase (PI4K) with an IC₅₀ value of 1.5 nM. KDU691 is selective for P. vivax PI4K over recombinant human PI4KβIII and PI3Kα, -β, -γ, 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). It is active against P. falciparum and P. yoelii schizonts (IC₅₀s = 0.06 and 0.04 μM, respectively), as well as P. cynomolgi schizonts and hypnozoites (IC₅₀s = 0.11 and 0.2 μM, respectively). KDU691 completely prevents, but does not eradicate established, P. cynomolgi infection in rhesus monkeys when administered at a dose of 20 mg/kg.

Uses

KDU691, is a PI4K inhibitor.

in vivo

During the 5 days of dosing, no major weight changes are observed in the animals that receive KDU691 as prophylactic treatment (group 691-proph). From the fourth day of dosing, the animals that are treated with KDU691 show a transient yellow skin color. 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^[2].

IC 50

Plasmodium

References

[1] CASE W. MCNAMARA. Targeting Plasmodium PI(4)K to eliminate malaria[J]. Nature, 2013, 504 7479: 248-253. DOI: 10.1038/nature12782
[2] BIN ZOU*. Lead Optimization of Imidazopyrazines: A New Class of Antimalarial with Activity on Plasmodium Liver Stages[J]. ACS Medicinal Chemistry Letters, 2014, 5 8: 947-950. DOI: 10.1021/ml500244m
[3] A. ZEEMAN. PI4 Kinase Is a Prophylactic but Not Radical Curative Target in Plasmodium vivax-Type Malaria Parasites[J]. Antimicrobial Agents and Chemotherapy, 2016, 60 1: 2858-2863. DOI: 10.1128/aac.03080-15

KDU691 Supplier

KDU691 manufacturers

Related Product Information

Send Inquriy