Previously, we revealed the dual enhancing effect of netoglitazone, an agonist of the peroxisome proliferator‐activated receptor γ, on adipogenesis and osteoblastogenesis, and reported that fatty acid synthase (FASN) knockdown selectively repressed its pro‐adipogenic effect. Here, we examined if a FASN inhibitor, C75, could selectively repress the pro‐adipogenic effect of netoglitazone. Surprisingly, C75 promoted the adipogenic differentiation of multipotent C3H10T1/2 cells but inhibited 3T3‐L1 preadipocytes. By identifying glycogen synthase kinase‐3β and intracellular cAMP levels as regulatory targets of C75, we ultimately found the differential expression of adenosine receptor 3 (AR3) and AR2a on these cells. Inhibition of AR3 on C3H10T1/2 and AR2a on 3T3‐L1 inhibited the effects of C75 on the differentiation of these cells. Our findings imply that cell‐type‐specific AR expression might account for the differential adipogenic effects of C75.

20 Apr 2019·AgingQ3 · MEDICINE

Cooperative impact of thiazolidinedione and fatty acid synthase on human osteogenesis

Q3 · MEDICINE

Article

Author: Lin, Feng-Huei ; Chen, Zih-Ying ; Wong, Zhe-Hong ; Chen, Ya-Ping ; Tseng, Kuo-Yun ; Wu, Hung-Ming ; Chen, Ching-Yun ; Chen, Ting-Yu ; Lin, Shankung ; Chen, Hsuan-Ying

Previous, we found that the small molecules capable of inhibiting the expression and the pro-adipogenic activity of ZNF521 might improve the osteogenic performance of aging human bone marrow MSCs (bmMSCs), and that fatty acid synthase (FASN) was a critical effector of ZNF521's pro-adipogenic activity. Here, by characterizing the netoglitazone (MCC-555), one of the thiazolidinediones known as adipogenic enhancers, as an inhibitor of ZNF521 expression, we found that MCC-555 indeed also harbored pro-osteoblastic effect. Investigation revealed that MCC-555 might function as a GSK3β inhibitor to promote osteoblastogenesis and bone formation. Importantly, combination of MCC-555 with FASN knockdown, but not with GW9662 (a PPARγ2 antagonist), blocked the pro-adipogenic but retained the pro-osteoblastic effect of MCC-555. Using a 3-dimentional culture system, we showed that MCC-555 facilitated the FASN-knockdown of aging human bmMSCs to form cell clusters in scaffolds, and to promote osteoblastic differentiation and biomineralization in cell clusters. These data indicated that MCC-555 promoted bmMSCs to produce bone-like tissues. Our data narrate a thiazolidinedione-based novel strategy to improve the osteogenic performance of aging bmMSCs to support the application of autologous aging bmMSCs in cell therapy and in producing bone-like tissues for repairing bone injury in the elderly.

02 Jul 2018·Current Drug Discovery Technologies

A Retrospect Study on Thiazole Derivatives as the Potential Antidiabetic Agents in Drug Discovery and Developments

Review

Author: Khatik, Gopal L. ; Mittal, Amit ; Kaur, Paranjeet ; Nayak, Surendra Kumar ; Ahsan, Waquar ; Vyas, Manish ; Datusalia, Ashok Kumar

BACKGROUNDHeterocycles containing thiazole, a moiety with sulfur and nitrogen is a core structure which is found in a number of biologically active compounds. The thiazole ring is notable as a component of the certain natural products, such as vitamin B1 (thiamine) and penicillins. Thiazole is also known as wonder nucleus and has uses in different biological fields. A number of new compounds contain heterocycle thiazole moieties, thus it is one of the important areas of research.METHODSWe searched the scientific database using relevant keywords. Among the searched literature only peer-reviewed papers were collected which addresses our questions. The retrieved quality research articles were screened and analyzed critically. The key findings of these studies were included along with their importance.RESULTSThe quality research articles included in this review were selected for the lifethreatening diseases i.e. diabetes, which is one of the serious issues all over the globe with an estimated worldwide prevalence in 2016 of 422 million people, which is expected to rise double to by 2030. Since 1995, there has been an explosion of the introduction of new classes of pharmacological agents having thiazole moieties. However, most of the drugs can cause noncompliance, hypoglycemia, and obesity. Thus, new antidiabetic drugs with thiazole moieties came up with improved compliance and reduced side effects such as pioglitazone (Actos), rosiglitazone (Avandia), netoglitazone, DRF-2189, PHT46, PMT13, DRF-2519. With such a great importance, research in thiazole is part of many academic and industrial laboratories worldwide.CONCLUSIONThe present review describes the importance of thiazole nucleus and its derivatives as antidiabetic agents with an emphasis on the past as well as recent developments.

100 Deals associated with Netoglitazone

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KEGG	Wiki	ATC	Drug Bank
D05150	Netoglitazone	-	DB09199

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	-	Mitsubishi Tanabe Pharma Corp.	-
Diabetes Mellitus, Type 2	Phase 2	JP	Mitsubishi Pharma Corp.	-

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