Table 1.

Summary of publications that used PKR inhibitor imidazolo-oxindole compound also known as C16 or Imoxim, which acts as an ATP-binding site directed inhibitor of PKR.

Field	Mode of administration	Concentration used	Model	Readout	Disease	Reference
Metabolism	Not given	5 μM for cells treatments	H9C2 cells treated with high concentrated glucose	Levels of pJNK/JNK↓,PKR↓and Caspase 3↓, mRNA levels of NFκB↓, JNK↓ and caspase-3↓. Measurements of ROS↓, nitrite levels↓, LDH↓	Diabetes	Udumula et al., 2018
	NA	5 μM (Imoxim)	NRK-52E cells treated with high fructose	Levels of PKR↓, caspase 3↓, Measurements of ROS levels↓. Apoptosis↓, JNK↓	Hypertension	Kalra et al., 2018
	Subcutaneous injection (Imoxim)	0.5 mg/kg (Imoxim)	Lean and obese male mice and MEF with TNFα	Glucose homeostasis↑ TNFα↓ and IL-6↓ mRNA in WTA. In MEF pPKR/PKR↓, pJNK/JNK↓, pIRS1S307/IRS1↓	Obesity	Nakamura et al., 2014
Immunology	NA	C16 400nM	THP1 macrophages	mRNA levels of GADD34↓, IL-8↓, IL-β↓	Inflammation	Dabo et al., 2017
	i.p.	100–500 μg/kg	Male BALB/C mice (7–8 weeks old) treated with intratracheal administration of LPS	Levels of TNF-α↓,IL-1β↓, IL-6↓, pPKR/actin↓, pIKK/IKK↓, pIkBα/IκB↓, pNFκB/actin↓, caspase3↓. Apoptosis↓ assessed by TUNEL↓ and pPKR↓ and pNFκB↓ by immunohistochemistry analysis. Analysis of lung injury↓ by hematoxylin and eosin stain	Acute lung injury	Li et al., 2017
	i.p.	150 μg/kg	Male SD Rats treated with Freund’s adjuvant	Limb swelling↓. Protein and mRNA levels a of HMGB1↓ and PKR↓ in blood and synovium	Rheumatoid arthritis	Wang et al., 2015
	NA	500 nM	mDC and BMDM derived from cybb+/+, cybb-/- mice, pkr+/+ and pkr-/-	IFNβ mRNA↓ and pPKR/PKR↓	Parasite infection (Chlamydia trachomatis)	Webster et al., 2016
Neuroscience	NA	500 nM	SH-SYSY and UM1242-G cells exposed to EtOH	Cell viability↑	Alcohol use	Duncan et al., 2016
	i.p.	600 μg/Kg	Male Wistar rats treated with QA	Levels of pPKR/PKR↓, peIF2α/eIF2α↓. Assessment of neurodegeneration by hematoxylin and eosin stain↓. Immunofluorescence of cleaved caspase-3↓	Neuroinflammation	Tronel et al., 2014
	NA	1 μM	Hippocampus-derived neuronal culture treated with AβO	Synapse loss↓ assessed by immunocytochemistry against synapsin and PSD95	Alzheimer’s disease and diabetes	Lourenco et al., 2013
	i.p.	0.5 μ/kg	APPswePS1dE9	Levels of pPKRT451/PKR↓, pNFκBS536/NFκB↓, BACE↓ and TNFα mRNA↓, IL-1β mRNA↓	Alzheimer’s disease	Couturier et al., 2012
	NA	210 nM	Primary murine mixed co-cultures treated with Aβ42	Levels of pPKRT451/Actin↓, pNFκBS536/NFκB↓, pIκB32/36/IκB↓, pro-caspase3/cleaved caspase3↓ and levels of TNFα↓, IL-1β↓, IL-6↓	Alzheimer’s disease	Couturier et al., 2011
	i.p.	0.27 mg/kg	Mice treated with 3-NP	Assessment of neurodegeneration↓ by Cresyl violet staining	Huntington’s disease	Chen et al., 2008
	NA	500 nM	Cerebellar granular neurons from rats treated with amprolium (thiamine depletion)	Levels of peIF2α/eIF2α↓ and cell viability↑	Vitamin B1 deficiency	Wang et al., 2007
	i.p.	0.335, 3.35, 33.5, or 167.5 μg/kg	Sprague-Dawley rats (7 days old, 1, 2, 4, 6, 9, and 12 months old)	Levels of pPKRThr446/PKR↓, peIF2α/eIF2α↓, pmTOR/mTOR (-), p70S6KThr389/p70S6K(-) and pPERK/PERK(-)	Neuroprotection	Ingrand et al., 2007
	i.p. and local microinjection	167.5 μ/kg, 50 μM for hippocampal slices and local injection	Male Wistar rats, PKR-KO and WT (129SvEv) Hippocampal slices	CTA↑, NT↑ Levels of peIF2α/eIF2α↓, pPKRThr451/PKR↓	Memory	Stern et al., 2013
	i.p.	0.1 mg/kg	Ifn-γ-/- and WT CF57BL/6 mice	Synchronized EEG and inhibition↓, FC (Auditory and Context)↑	Memory	Zhu et al., 2011

The inhibitor C16 was acquired from Calbiochem (cat. # 527450) or from Sigma Aldrich (cat. # I9785). ↑ up-regulation. ↓ down-regulation. (-) no change. NOR, Novel Objet Recognition; FC, Fear conditioning; MWM, Morris Water Maze; mDC, human monocyte-derived dendritic cells; BMDM, murine bone marrow derived monocytes; CTA, Conditioned taste aversion; NT, Novel taste; WAT, white adipose tissue; MEF, Mice Embryonic Fibroblasts; QA, quinolinic acid; NA, not applicable; AβO, Aβ oligomers.