t-0070907 and Diabetes-Mellitus--Type-2

t-0070907 has been researched along with Diabetes-Mellitus--Type-2* in 2 studies

Other Studies

2 other study(ies) available for t-0070907 and Diabetes-Mellitus--Type-2

Article	Year
Arylalkynyl amide-type peroxisome proliferator-activated receptor γ (PPARγ)-selective antagonists covalently bind to the PPARγ ligand binding domain with a unique binding mode. Bioorganic & medicinal chemistry letters, 2022, 05-15, Volume: 64 Peroxisome proliferator-activated receptor γ (PPARγ) antagonists are drug candidates for the treatment of type 2 diabetes, obesity, and osteoporosis. Previously, we have designed and synthesized a series of substituted phenylalkynyl amide-type PPARγ antagonists. The representative compound, MMT-160, exhibited nanomolar-order PPARγ antagonistic activity. To understand the antagonistic mode of action of MMT-160, mass spectrometric and X-ray crystallographic analysis of MMT-160 in the presence of the PPARγ ligand binding domain (LBD) were performed. The mass spectrometry results clearly indicated that alkynyl amide-type PPARγ antagonists were covalently bound to the PPARγ LBD. The X-ray crystallographic analysis indicated that MMT-160 acted as a Michael acceptor and covalently bound to the PPARγ LBD via Cys285. In addition, MMT-160 bound to the PPARγ LBD with a binding mode that was different from the binding modes observed for PPARγ agonists and partial agonists. Topics: Amides; Diabetes Mellitus, Type 2; Humans; Ligands; PPAR gamma; Protein Domains	2022
Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ. Biochemistry, 2015, Nov-17, Volume: 54, Issue:45 Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. Topics: Benzamides; Carotid Artery Diseases; Cell Differentiation; Cells, Cultured; Chemotaxis; Combined Modality Therapy; Depression, Chemical; Diabetes Mellitus, Type 2; Down-Regulation; Endarterectomy, Carotid; Gene Expression Regulation; Humans; Macrophages; Pioglitazone; PPAR alpha; PPAR gamma; Pyridines; Receptors, CXCR; RNA Interference; RNA, Small Interfering; Rosiglitazone; Thiazolidinediones	2015

Article

Year

Arylalkynyl amide-type peroxisome proliferator-activated receptor γ (PPARγ)-selective antagonists covalently bind to the PPARγ ligand binding domain with a unique binding mode.

Bioorganic & medicinal chemistry letters, 2022, 05-15, Volume: 64

Peroxisome proliferator-activated receptor γ (PPARγ) antagonists are drug candidates for the treatment of type 2 diabetes, obesity, and osteoporosis. Previously, we have designed and synthesized a series of substituted phenylalkynyl amide-type PPARγ antagonists. The representative compound, MMT-160, exhibited nanomolar-order PPARγ antagonistic activity. To understand the antagonistic mode of action of MMT-160, mass spectrometric and X-ray crystallographic analysis of MMT-160 in the presence of the PPARγ ligand binding domain (LBD) were performed. The mass spectrometry results clearly indicated that alkynyl amide-type PPARγ antagonists were covalently bound to the PPARγ LBD. The X-ray crystallographic analysis indicated that MMT-160 acted as a Michael acceptor and covalently bound to the PPARγ LBD via Cys285. In addition, MMT-160 bound to the PPARγ LBD with a binding mode that was different from the binding modes observed for PPARγ agonists and partial agonists.

Topics: Amides; Diabetes Mellitus, Type 2; Humans; Ligands; PPAR gamma; Protein Domains

2022

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ.

Biochemistry, 2015, Nov-17, Volume: 54, Issue:45

Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ.

Topics: Benzamides; Carotid Artery Diseases; Cell Differentiation; Cells, Cultured; Chemotaxis; Combined Modality Therapy; Depression, Chemical; Diabetes Mellitus, Type 2; Down-Regulation; Endarterectomy, Carotid; Gene Expression Regulation; Humans; Macrophages; Pioglitazone; PPAR alpha; PPAR gamma; Pyridines; Receptors, CXCR; RNA Interference; RNA, Small Interfering; Rosiglitazone; Thiazolidinediones

2015