PK 11195, a ligand of this protein, acts as an anti-leishmanial agent.

At the same time, PK 11195 exhibits IC₅₀ values of 14.2 μM for L. amazonensis, 8.2 μM for L. major, and 3.5 μM for L. braziliensis, respectively. The selective index value for L. amazonensis is 13.7, indicating the safety of PK 11195 for future testing in mammals. PK11195 was found to reduce the viability of axenic promastigotes of three Leishmania species, which are known to cause cutaneous leishmaniasis, in a dose-dependent manner with low IC₅₀/48 h values.

Moreover, the percentage of infected cells significantly reducts after 48 h, with a median value of 1.37% (IQR = 0.68-2.05) for cells treated with 100 µM PK11195, compared with 86.88% (IQR = 81.5-90.94) for the control group.

Strikingly, the IC₅₀/48 h value pertaining to the effect on intracellular amastigotes of treatment with PK11195 at concentrations rangs from 6.25 to 175 µM was 46.55 ± 11.88 µM, almost four times lower than the CC₅₀/48 h value obtained in macrophages.

Again, Pre-treatment of macrophages with 75 µM PK11195 prior to Leishmania infection resulted in a significant reduction in O2 ●- production by plasma-membrane NADPH-dependent oxidase. Moreover, pre-treatment with 75 µM PK11195 results in a 5.0-fold reduction in O2 ●- production with LPS (500 ng/mL). This results in O2 ●- levels similar to those produced by untreated control macrophages.

PK11195 also acts as a specific PBR ligand.

PK11195 attenuates the occurrence of seizures, hyperactivity. It also increases in isoquinoline binding protein levels in the hippocampus, which usually follow kainic acid application.

Moreover, PK11195 and other ligands are currently being used as markers of neuroinflammation in PET imaging. PK11195, may act as agonists or antagonists depending on the ligand concentration and cell type.

Reference:

Guedes CES, et al. In vitro evaluation of the anti-leishmanial activity and toxicity of PK-11195. Mem Inst Oswaldo Cruz. 2018 Feb 5;113(4):e170345.

L Veenman, et al. PK 11195 attenuates kainic acid-induced seizures and alterations in peripheral-type benzodiazepine receptor (PBR) protein components in the rat brain.