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Chemical Structure| 654671-77-9 Chemical Structure| 654671-77-9
Chemical Structure| 654671-77-9

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CAS No.: 654671-77-9

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Sitagliptin Phosphate Monohydrate is a potent inhibitor of DPP4 with IC50 of 19 nM in Caco-2 cell extracts.

Synonyms: MK-0431; MK-0431 phosphate monohydrate

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Mani, Vasudevan ; Arfeen, Minhajul ;

Abstract: Background/Objectives: Diabetes mellitus (DM), a widespread endocrine disorder charac_x005f_x0002_terized by chronic hyperglycemia, can cause nerve damage and increase the risk of neurodegenerative diseases such as Alzheimer’s disease (AD). Effective blood glucose management is essential, and sitagliptin (SITG), a dipeptidyl peptidase-4 (DPP-4) inhibitor, may offer neuroprotective benefits in type 2 diabetes mellitus (T2DM). Methods: T2DM was induced in rats using nicotinamide (NICO) and streptozotocin (STZ), and biomarkers of AD and DM-linked enzymes, inflammation, oxidative stress, and apoptosis were evaluated in the brain. Computational studies supported the in vivo findings. Results: SITG significantly reduced the brain enzyme levels of acetylcholinesterase (AChE), beta-secretase-1 (BACE-1), DPP-4, and glycogen synthase kinase-3β (GSK-3β) in T2DM-induced rats. It also reduced inflammation by lowering cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). Additionally, SITG improved oxidative stress markers by reducing malondialdehyde (MDA) and enhancing glutathione (GSH). It increased anti-apoptotic B-cell lymphoma protein-2 (Bcl-2) while reducing pro-apoptotic markers such as Bcl-2-associated X (BAX) and Caspace-3. SITG also lowered blood glucose levels and improved plasma insulin levels. To explore potential molecular level mechanisms, docking was performed on AChE, COX-2, GSK-3β, BACE-1, and Caspace-3. The potential binding affinity of SITG for the above-mentioned target enzymes were 10.8, 8.0, 9.7, 7.7, and 7.9 kcal/mol, respectively, comparable to co-crystallized ligands. Further binding mode analysis of the lowest energy conformation revealed interactions with the critical residues. Conclusions: These findings highlight SITG’s neuroprotective molecular targets in T2DM-associated neurodegeneration and its potential as a therapeutic approach for AD, warranting further clinical investigations.

Keywords: sitagliptin ; type 2 diabetes mellitus ; Alzheimer’s disease ; brain enzymes ; inflammation ; oxidative stress ; apoptosis ; molecular docking

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Product Details of [ 654671-77-9 ]

CAS No. :654671-77-9
Formula : C16H20F6N5O6P
M.W : 523.32
SMILES Code : O=C(N1CC2=NN=C(C(F)(F)F)N2CC1)C[C@H](N)CC3=CC(F)=C(F)C=C3F.O=P(O)(O)O.[H]O[H]
Synonyms :
MK-0431; MK-0431 phosphate monohydrate
MDL No. :MFCD19684081
InChI Key :GQPYTJVDPQTBQC-KLQYNRQASA-N
Pubchem ID :11591741

Safety of [ 654671-77-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310
 

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