transgenic

PD146176 (NSC-168807) is an inhibitor of 15-Lipoxygenase (15-LO) , it inhibits rabbit reticulocyte 15-LO with Ki of 197 nM and IC50 of 0.54 μM. PD146176 reverses cognitive impairment, brain amyloidosis, and tau pathology by stimulating autophagy in aged triple transgenic mice.

DGAT-1 inhibitor 2 is an effective DGAT-1 inhibitor and anti-obesity drug. DGAT-1 (acyl-CoA: diacylglycerol acyltransferase 1) is one of two known DGAT enzymes that catalyze the final step of triglyceride synthesis. Transgenic mice and pharmacological studies indicate that inhibiting DGAT1 is a promising strategy for treating obesity and type 2 diabetes.

BMS 433796 is a γ-secretase inhibitor that demonstrates Aβ-lowering activity in a transgenic mouse model of Alzheimer's disease.

GSK-3 inhibitor 3 is a selective, orally active, brain-permeable GSK-3 inhibitor that inhibits GSK-3α and GSK-3β with IC50s of 0.35 nM and 0.25 nM, respectively.GSK-3 inhibitor 3 reduces the phosphorylation level of tau protein S396 with an IC50 of 10 nM in a triple transgenic mouse model of Alzheimer's disease. GSK-3 inhibitor 3 reduced the phosphorylation level of tau protein S396 in a triple transgenic mouse model of Alzheimer's disease, with an IC50 of 10 nM.GSK-3 inhibitor 3 can be used for the study of neurological diseases.

Tamoxifen Citrate is an orally active selective estrogen receptor modulator (SERM) that blocks estrogen activity in breast cells while activating estrogen signaling in cells such as those of the bone, liver, and uterus. As an Hsp90 activator, it enhances the ATPase activity of the Hsp90 chaperone complex, induces autophagy and apoptosis, and can be used to generate gene knockout models in CreER(T2) transgenic mice as well as liver injury models.

1. Octyl Gallate is an antioxidant approved by the US Food and Drug Administration (FDA) as a food additive. 2. Octyl Gallate has antimetastatic activity. 3. Octyl Gallate shows antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 ug/mL. 4. Combination therapy with octyl gallate and ferulic acid improves cognition and neurodegeneration in a transgenic mouse model of Alzheimer's disease.5. Octyl Gallate is a potential anticancer agent, it exhibited decreased MCF-7 & MDA-MB-231 survival and induced apoptosis, with IC50 value of 40 uM. 6. Octyl gallate (Octyl 3,4,5-trihydroxybenzoate) has antiviral activity, it shows an inhibitory effect on the growth of herpes simplex virus type 1 (HSV-1) in HEp-2 or Vero cells. 7. Octyl gallate shows antifungal activity against Saccharomyces cerevisiae ATCC7754 and Zygosaccharomyces bailii ATCC 60483.

D-688 serves as an inhibitor of Tau and Aβ. It can reverse the cytotoxicity in SH-SY5Y cells induced by Aβ1–42, displaying significant neuroprotective characteristics. Additionally, D-688 enhances the survival rate of transgenic fruit flies expressing the human tau protein isoform (2N4R).

Nav1.7-IN-18 (Compound 31) is a Nav1.7 inhibitor with a Ki value of 4.9 nM and an IC50 of 13 nM, demonstrating analgesic effects in transgenic mice with inherited erythromelalgia (IEM).

TKB272 is an orally active antiviral agent that selectively targets the main protease (Mpro) of SARS-CoV-2, effectively inhibiting the infection and replication of various strains, including Omicron variants (such as XBB.1.5 and EG.5.1). It exhibits an enzyme inhibitory activity with an IC50 of 0.7 µM against SARS-CoV-2WK-521 Mpro and shows potent antiviral activity at the cellular level with an EC50 as low as 2.6 nM in HeLahACE2-TMPRSS2 cells against the BQ.1.1 strain. TKB272 also has a CC50 of 98 µM, indicating low cytotoxicity. Furthermore, it demonstrates a significant suppression of SARS-CoV-2XBB.1.5 replication in the B6.Cg-Tg(K18-hACE2)2-Prlmn/J transgenic mouse model, suggesting potential use in the research of SARS-CoV-2 infections.

Ponasterone A is an ecdysteroid with high affinity for the ecdysteroid receptor. It enables rapid switching on and off of reporter genes and is a potent regulator of gene expression in cells and transgenic animals.

PRT-060318 (PRT318) dihydrochloride is a potent, highly selective tyrosine kinase Syk inhibitor with an IC50 of 3 nM, and is orally bioavailable. It inhibits the activation and migration of B cells in chronic lymphocytic leukemia (CLL) and induces apoptosis. Additionally, PRT-060318 dihydrochloride offers potential therapeutic applications by preventing heparin-induced thrombocytopenia and thrombosis in transgenic mouse models, making it useful in studies of chronic lymphocytic leukemia and thrombosis.

Physostigmine is an alkaloid extracted from the poison bean (Physostigma venenosum) and acts as a reversible acetylcholinesterase (AChE) inhibitor. Physostigmine inhibits the action of acetylcholinesterase, increasing acetylcholine levels, and thus serves as an antidote for anticholinergic poisoning. Physostigmine crosses the blood-brain barrier and stimulates central cholinergic neurotransmission. Physostigmine can reverse memory deficits in transgenic mice with Alzheimer's disease.

Sudemycin D6 is a potent pre-mRNA splicing modulator with significant antitumor activity. It alters the splicing site utilization of DUSP11 and SRRM1 precursor mRNA. Sudemycin D6 reduces the survival rate and alters the cell cycle of hematopoietic cells expressing mutant U2AF1. It also diminishes mutant U2AF1-induced hematopoietic progenitor cell expansion in U2AF1(S34F) transgenic mice. Sudemycin D6 is applicable in cancer research.

JAY2-22-33, as a neuroprotective agent, can act by significantly reducing Aβ toxicity by delaying paralysis and improving cognitive performances in a transgenic mouse model of AD.

JWB1-84-1 3HCl, as a neuroprotective agent, can act by improving cognitive performances in a transgenic mouse model of AD.

OAB-14 is a Bexarotene derivative that improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. OAB-14 effectively ameliorates the dysfunction of the endosomal-autophagic-lysosomal(EAL) pathway in APP/PS1 transgenic mice [1] [2].

SAR502250 is a potent, selective, ATP-competitive, orally active, and brain-penetrant GSK3 inhibitor with a human GSK-3β IC50 value of 12 nM, exhibiting antidepressant-like activity and being researched for potential application in Alzheimer's disease (AD) treatment.

Pinolenic acid is a polyunsaturated fatty acid found in Korean pine (Pinus orientalis) and maritime pine (Pinus pinaster) seed oils, which exhibit lipid-lowering properties. In transgenic mice expressing human ApoA1, a diet containing maritime pine seed oil (MPSO) reduced high-density lipoprotein and ApoA1 levels and diminished cholesterol efflux in vitro. Korean pine seed oil supplements may aid in reducing obesity by decreasing appetite, as evidenced by increased levels of satiety hormones CCK and GLP-1 and reduced desire to eat. Pinolenic acid, which is not metabolically converted to arachidonic acid, can lower arachidonic acid levels in the phosphatidylinositol fraction of HepG2 cells from 15.9% to 7.0%. The neutral, more lipophilic form of pinolenic acid is pinolenic acid ethyl ester.

Peroxisome proliferator-activated receptors (PPARs) α, δ, γ are ligand-activated nuclear transcription factors involved in the regulation of energy homeostasis as well as insulin sensitivity and glucose metabolism. Pharmacologies of PPARδ receptor agonists, though relatively obscure, have recently been reported to elevate high-density lipoprotein (HDL) cholesterol and lower plasma triglyceride (TG) levels in obese insulin resistant rhesus monkeys. CAY10592 is a full PPARδ agonist (EC50 = 30 nM) in a fatty acid oxidation assay of rat L6 muscle cells with desirable oral pharmacokinetic properties. In a transactivation assay using human PPAR receptors, CAY10592 acts as a selective partial PPARδ agonist (EC50 = 53 nM) with no effect on PPARα or PPARγ activity up to 30 μM. Chronic treatment of high fat fed ApoB100/CETP-transgenic mice with CAY10592 at a dose of 20 mg/kg increases HDL levels, decreases LDL and TG levels, and improves insulin sensitivity.

AAA is an antagonist of G protein-coupled receptor 75 (GPR75).1It increases basal GPR75 protein levels and inhibits 20-HETE-induced reductions in GPR75 protein levels in PC3 cells. AAA (5 and 10 μM) also reduces 20-HETE-induced phosphorylation of EGFR, NF-κB, and Akt in, and cell migration of, PC3 cells.In vivo, AAA (10 mg/kg per day) reduces systolic blood pressure, albuminuria, renal angiotensin II levels, and cardiac hypertrophy in a Cyp1a1-Ren-2 transgenic rat model of malignant hypertension when administered prior to induction or after establishment of hypertension.2 1.Cárdenas, S., Colombero, C., Panelo, L., et al.GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cellsBiochim. Biophys. Acta Mol. Cell Biol. Lipids1865(2)158573(2020) 2.Sedláková, L., Kikerlová, S., Husková, Z., et al.20-Hydroxyeicosatetraenoic acid antagonist attenuates the development of malignant hypertension and reverses it once established: a study in Cyp1a1-Ren-2 transgenic ratsBiosci. Rep.38(5)BSR20171496(2018)

Ceramide phosphoethanolamine (CPE) is an analog of sphingomyelin that contains ethanolamine rather than choline as the head group. It is the principal membrane phospholipid in invertebrates such as Drosophila, which lacks sphingomyelin. It is only produced in small amounts in mammalian cells, accounting for approximately 0.02 mol% of total phospholipids in mouse testis and brain. In Drosophila, CPE is biosynthesized by CPE synthase from ceramide and cytidine diphosphate-ethanolamine in the Golgi lumen. In mammals, it is biosynthesized by sphingomyelin synthase 2 (SMS2) in the plasma membrane and by sphingomyelin synthase-related protein (SMSr) in the endoplasmic reticulum (ER). In Drosophila, CPE has a role in glial ensheathment of axons. Disrupting CPE synthesis by depleting SMSr in vitro in mammalian cells leads to an accumulation of ER ceramides, which are then mislocalized to the mitochondria, inducing apoptosis. However, ceramide levels are not altered in transgenic mice lacking SMSr catalytic activity. CPEs (bovine) is a mixture of CPEs with variable N-acyl chain lengths.

5(Z),11(Z),14(Z)-Eicosatrienoic acid is a polyunsaturated fatty acid found in various natural sources including maritime pine (Pinus pinaster) seed oil (MPSO), gymnospermae leaves and seeds, and freshwater gastropods. A diet containing MPSO lowered high-density lipoprotein and ApoA1 levels in transgenic mice expressing human ApoA1. MPSO was found to diminish cholesterol efflux in vitro. 5(Z),11(Z),14(Z)-Eicosatrienoic acid methyl ester, when topically applied, reduces inflammatory processes, potentially by displacing arachidonic acid from phospholipid pools and reducing downstream inflammatory products such as prostaglandin E2 and leukotrienes.

CuATSM is a cell-permeable copper complex and PET tracer for selective hypoxia imaging. It also exhibits neuroprotective potential in ALS and Parkinson's disease by mitigating oxidative damage.

Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988). Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4 References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988).