Pyruvate kinase (PK) catalyzes the last step of glycolysis and exists as four isoenzymes: PK, liver, PK, red blood cell, PK, muscle (PKM1 and PKM2). Pyruvate kinase isoenzyme type M2 (PKM2, M2-PK) plays a key role in modulating glucose metabolism to support cell proliferation. PKM2, like other PK isoforms, catalyzes the last energy-generating step in glycolysis, but is unique in its capacity to be regulated.[1]. PKR-IN-C16 is a specific protein kinase (PKR) inhibitor. PKR-IN-C16 is able to inhibit the autophosphorylation of PKR and unlock the translation blockade induced by PKR in primary neuronal cultures. It binds the ATP-binding site of PKR and blocks autophosphorylation with an IC50 value of 186-210 nM. PKR-IN-C16 protects human neuroblastoma cells against cell damage triggered by tunicamycin-mediated endoplasmic reticulum stress[2].
PKR-IN-C16 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HeLa cells
0-96 μM
2.5 hours
To evaluate the activation of GCN2 by the PKR inhibitor C16, results showed that C16 activated GCN2 between 0.19 to 1.5 μM and inhibited GCN2 at higher concentrations.
Nat Commun. 2023 Sep 8;14(1):5535.
Retinal endothelial cells
2 µM
To investigate whether PKR inhibition regulates the NLRP3 inflammasome pathway, results showed that PKR inhibition significantly reduced NLRP3, cleaved caspase 1, and IL-1β levels.
J Inflamm Res. 2019 Jun 12;12:153-159.
Retinal endothelial cells
2 µM
16 hours
To determine the optimal dose of C16 for inhibiting PKR phosphorylation, results showed that 2 µM C16 effectively reduced PKR phosphorylation.
J Inflamm Res. 2019 Jun 12;12:153-159.
U-2 OS cells
1μM
48 hours
C16 attenuates phosphorylation of p53 on Ser46 and Ser392 and prevents or attenuates upregulation of innate immunity genes.
Cell Signal. 2020 May;69:109552.
A549 cells
1μM
48 hours
C16 inhibits phosphorylation of p53 on Ser46 and Ser392 and prevents upregulation of innate immunity genes.
Cell Signal. 2020 May;69:109552.
Huh7 cells
0, 500, 1000, 2000, 3000 nM
24 hours
To evaluate the effect of C16 on HCC cell proliferation. C16 suppressed proliferation of HCC cells in a dose-dependent manner, with maximum effects seen at >2000 nM.
Sci Rep. 2020 Mar 20;10(1):5133.
HT29 cells
100, 500, 1000 nM
24 hours
C16 suppressed the proliferation of HT29 cells in a dose-dependent manner.
Sci Rep. 2024 Apr 19;14(1):9029.
HCT116 cells
100, 500, 1000 nM
24 hours
C16 suppressed the proliferation of HCT116 cells in a dose-dependent manner.
Sci Rep. 2024 Apr 19;14(1):9029.
PKR-IN-C16 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Tg26 transgenic mouse model
Intraperitoneal injection
10 µg/kg body weight
Three times weekly from 6 to 12 weeks of age
PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction.
Elife. 2024 Aug 29;12:RP91260
Nude mice
Xenograft model
Intraperitoneal injection
300 μg/kg
Once daily for 4 weeks
To evaluate the effect of C16 on HCC tumor growth. C16 significantly suppressed tumor growth and decreased angiogenesis in HCC tissue.
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