KLH45 Chemical Properties

Boiling point:

561.0±60.0 °C(Predicted)

Density 

1.29±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO:30.0(Max Conc. mg/mL);65.43(Max Conc. mM)
Ethanol:30.0(Max Conc. mg/mL);65.43(Max Conc. mM)

form 

Solid-Liquid Mixture

pka

-1.76±0.20(Predicted)

color 

Off-white to light yellow

KLH45 Usage And Synthesis

Description

KLH45 is an inhibitor of the phospholipase DDHD domain containing 2 (DDHD2; IC₅₀ = 1.3 nM). It is selective for DDHD2 over greater than 50 serine hydrolases, including DDHD1 and Sec23ip, but does inhibit α/β-hydrolase domain-containing protein 6 (ABHD6). It inhibits DDHD2 and ABHD6 in Neuro2A cells when used at a concentration of less than 10 nM and inhibits DDHD2 by greater than 95% at a concentration of 25 nM. KLH45 (2 μM) prevents increases in triacylglycerol (TAG) hydrolase activity in HEK293T cell lysates expressing recombinant DDHD2 and incubated with a radiolabeled TAG substrate. It decreases TAG levels in the CNS of mice when administered at a dose of 20 mg/kg twice per day for four days. KLH45 (2 μM) also reverses DDHD2-induced lipid droplet reduction in COS-7 cells expressing recombinant DDHD2 and loaded with oleic acid.

Uses

KLH45 is a novel selective inhibitor of DDHD2.

in vivo

References

[1] JORDON M INLOES. The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111 41: 14924-14929. DOI: 10.1073/pnas.1413706111
[2] JORDON M. INLOES,  Benjamin F. Cravatt*. Functional Contribution of the Spastic Paraplegia-Related Triglyceride Hydrolase DDHD2 to the Formation and Content of Lipid Droplets[J]. Biochemistry Biochemistry, 2017, 57 5: 827-838. DOI: 10.1021/acs.biochem.7b01028