Journal: Frontiers in Behavioral Neuroscience

Article Title: Intranasal Neuropeptide Y as a Potential Therapeutic for Depressive Behavior in the Rodent Single Prolonged Stress Model in Females

doi: 10.3389/fnbeh.2021.705579

Figure Lengend Snippet: Effects of NPY processing on the high dose requirement for prevention of stress-elicited behavior. The experimental protocol is shown (A) . Animals were infused intranasally with either the vehicle for OMR and NPY (SPS/V), NPY 600 μg (SPS/NPY 600 μg ), dipeptidyl peptidase IV inhibitor omarigliptin (SPS/OMR), or both (SPS/OMR+NPY) immediately after the SPS stressors. The SPS/NPY 600 μg and SPS/OMR groups also received the vehicle for the other drug treatment given as separate infusions (SDS = OMR vehicle; dH 2 O = NPY vehicle). Alongside unstressed controls, the animals were tested for social interaction, anxiety on the EPM, and depressive-like behavior on the FST 19, 21, and 28 days after the SPS stressors, respectively. The animals were measured for (B) percent duration immobile on the FST and (C) percent duration social interaction. On the EPM, animals were tested for (D) percent entries into the open arms (OA); (E) percent duration in the OA; (F) anxiety index. Each point represents values for an individual animal. Means ± SEM are shown. One-way ANOVA was performed and post hoc Tukey was used to determine differences between groups. * p < 0.05, ** p < 0.01.

Article Snippet: Rats while under the influence of ether (the last SPS stressor) were administered a single intranasal infusion of NPY (ABclonal Science Inc., Woburn, MA, USA) freshly dissolved in distilled water and/or 1,200 μg omarigliptin (Selleck Chemicals, Houston, TX, USA) dissolved in 2.5% ( w/v ) sodium dodecyl sulfate.

Techniques:

Journal: Frontiers in Behavioral Neuroscience

Article Title: Intranasal Neuropeptide Y as a Potential Therapeutic for Depressive Behavior in the Rodent Single Prolonged Stress Model in Females

doi: 10.3389/fnbeh.2021.705579

Figure Lengend Snippet: Schematic of intranasal NPY treatment and role of NPY cleavage in females. (A) The first 2 N-terminal amino acids of NPY are cleaved by dipeptidyl peptidase IV (DPP4), changing it from a pan-receptor agonist to a Y2R and Y5R selective agonist. Omarigliptin (OMR) blocks the activity of DPP4, preventing NPY’s cleavage. (B) Without any exogenous delivery of the drug, DPP4 cleaves NPY resulting in a low concentration of the full-length NPY peptide. (C) Delivery of a high dose of intranasal NPY rapidly reaches the central nervous system and results in a higher concentration of the full-length NPY peptide in the synapse, despite some cleavage by DPP4. (D) Intranasal administration of OMR and a lower dose of NPY results in a similar concentration of the full-length NPY peptide as compared to delivery of a high dose of intranasal NPY in part due to the inhibition of its cleavage. Higher synaptic availability of the full-length NPY peptide is likely able to have greater activation of Y1R, compared to the NPY cleavage product. Illustration created with BioRender © .

Article Snippet: Rats while under the influence of ether (the last SPS stressor) were administered a single intranasal infusion of NPY (ABclonal Science Inc., Woburn, MA, USA) freshly dissolved in distilled water and/or 1,200 μg omarigliptin (Selleck Chemicals, Houston, TX, USA) dissolved in 2.5% ( w/v ) sodium dodecyl sulfate.

Techniques: Activity Assay, Concentration Assay, Inhibition, Activation Assay

Journal: Biochemical Pharmacology

Article Title: Dipeptidyl peptidase 4 inhibitors: Applications in innate immunity?

doi: 10.1016/j.bcp.2021.114517

Figure Lengend Snippet: Selective DPP4 inhibitors approved for the clinical management of type-2 diabetes.

Article Snippet: Omarigliptin (MK-3102) , Merck & Co , Japan 2015 , , 1.6 , >6.7x10 4 , >6.7x10 4 , .

Techniques:

Journal: Cell reports

Article Title: Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer

doi: 10.1016/j.celrep.2023.113198

Figure Lengend Snippet: KEY RESOURCES TABLE

Article Snippet: Omarigliptin , Cayman Chemical , Cat# 1226781-44-7.

Techniques: Recombinant, Protease Inhibitor, Plasmid Preparation, SYBR Green Assay, ISH Cell Assay, Sequencing, Software

Journal: Current Diabetes Reviews

Article Title: Addressing Unmet Medical Needs in Type 2 Diabetes: A Narrative Review of Drugs under Development

doi: 10.2174/1573399810666141224121927

Figure Lengend Snippet: Marketed Drugs for T2D.

Article Snippet: The once-weekly dipeptidyl peptidase-4 (DPP4) inhibitors omarigliptin (Merck - ML-3102) and trelagliptin (Takeda - SYR-472) are currently in Phase 3 development.

Techniques: Activation Assay, Modification