PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists), PPARγ partial agonists(Peroxisome proliferator-activated receptor γ partial agonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 2

Inactive Indication-

Originator Organization

Dr. Reddy's Laboratories Ltd.

Active Organization

Nordic Bioscience A/S

Inactive Organization

CCBR Clinical Research (Beijing) Co., Ltd.Rheoscience Aps

Dr. Reddy's Laboratories Ltd.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

Structure

Molecular FormulaC20H17N3O4S

InChIKeyIETKPTYAGKZLKY-UHFFFAOYSA-N

CAS Registry199113-98-9

Clinical Trials associated with Balaglitazone

NCT00515632 / CompletedPhase 3

A Randomized, Double-blind, Parallel-group, Placebo and Active Comparator (Pioglitazone)-Controlled Clinical Study to Determine the Efficacy and Safety of Balaglitazone in Patients With Type 2 Diabetes on Stable Insulin Therapy

Type 2 diabetes mellitus is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. People with type 2 diabetes are at high risk of many serious diabetic complications, including cardiovascular disease, blindness, nerve damage and kidney damage. Balaglitazone is a thiazolidinedione derivative that is being developed as an oral anti-diabetic drug to improve blood glucose control in patients with type 2 diabetes. The purpose of this study is to assess if additional treatment with balaglitazone in patients with type 2 diabetes on stable insulin treatment will improve blood glucose control and decrease the daily insulin dose compared to placebo, but with less impact on weight gain and oedema than pioglitazone (Actos®) 45 mg.

Start Date01 Jul 2007

Sponsor / Collaborator

Rheoscience Aps

100 Clinical Results associated with Balaglitazone

100 Translational Medicine associated with Balaglitazone

100 Patents (Medical) associated with Balaglitazone

Literatures (Medical) associated with Balaglitazone

01 Oct 2017·Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

Balaglitazone reverses P-glycoprotein-mediated multidrug resistance via upregulation of PTEN in a PPARγ-dependent manner in leukemia cells

Article

Author: Azimi, Ako ; Yousefi, Bahman ; Badalzadeh, Reza ; Samadi, Nasser ; Majidinia, Maryam ; Baradaran, Behzad ; Shafiei-Irannejad, Vahid ; Zarghami, Nosratollah

Multidrug resistance in tumor cells is still a big challenge in cancer treatment. Therefore, identification ofsafe and effective multidrug resistance-reversing compounds with minimal side effects is an important approach in cancer treatment. Here, we investigated the role and potential mechanisms of peroxisome proliferator-activated receptor γ in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. The effect of doxorubicin on cell viability following treatment with balaglitazone, a peroxisome proliferator-activated receptor γ agonist, was evaluated using trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Rhodamine123 assay was used to determine the activity of two common drug efflux membrane transporters P-glycoprotein and multidrug resistance protein-1. P-glycoprotein, multidrug resistance protein-1, and phosphatase and tensin homolog deleted on chromosome 10 messenger RNA/protein expression levels were measured by quantitative reverse transcription polymerase chain reaction and western blot analyses. Annexin V/fluorescein isothiocyanate assay was also employed to investigate apoptosis. We showed that balaglitazone considerably enhanced the cytotoxicity of doxorubicin. Balaglitazone also significantly downregulated P-glycoprotein expression and activity in K562/DOX cells and reduced multidrug resistance through elevation of intracellular doxorubicin in cells. Furthermore, upon balaglitazone treatment, phosphatase and tensin homolog deleted on chromosome 10 expression could be restored in K562/DOX cells in a peroxisome proliferator-activated receptor γ-dependent manner. We concluded that peroxisome proliferator-activated receptor γ agonist, balaglitazone, could reverse multidrug resistance by inducing phosphatase and tensin homolog deleted on chromosome 10 and peroxisome proliferator-activated receptor/ phosphatase and tensin homolog deleted on chromosome 10 signaling pathway. These findings suggest that targeting peroxisome proliferator-activated receptor γ might serve as an effective approach for circumventing multidrug resistance in chemotherapy of cancerous patients.

01 Jan 2017·DiabetologiaQ1 · MEDICINE

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

Q1 · MEDICINE

Article

Author: Genovese, Federica ; Riis, Bente J ; Nielsen, Mette J ; Byrjalsen, Inger ; Henriksen, Kim ; Schuppan, Detlef ; Leeming, Diana J ; Christiansen, Claus ; Karsdal, Morten A

AIMS/HYPOTHESIS:

The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of procollagen type VI (also called Pro-C6), is involved in both adipose tissue matrix remodelling and metabolic control. We established a serum assay for endotrophin to assess if this novel adipokine could identify type 2 diabetic patients who respond optimally to PPARγ agonists, improving the risk-to-benefit ratio.

METHODS:

The BALLET trial (NCT00515632) compared the glucose-lowering effects and safety of the partial PPARγ agonist balaglitazone with those of pioglitazone in individuals with type 2 diabetes on stable insulin therapy. The per protocol population (n = 297) was stratified into tertiles based on baseline endotrophin levels. Participants were followed-up after 26 weeks, after which correlational analysis was carried out between endotrophin levels and measures of glucose control. This is a secondary post hoc analysis.

RESULTS:

Endotrophin was significantly associated with therapeutic response to balaglitazone and pioglitazone. At week 26, only individuals in the upper two tertiles showed significant reductions in HbA_1c and fasting serum glucose compared with baseline. The OR for a 1% and a 0.5% reduction in HbA_1c for individuals in the upper two tertiles were 3.83 (95% CI 1.62, 9.04) p < 0.01, and 3.85 (95% CI 1.94, 7.61) p < 0.001, respectively. Endotrophin levels correlated with adipose tissue mass, insulin resistance and fatty liver index. Notably, PPARγ-associated adverse effects, such as moderate-to-severe lower extremity oedema, only occurred in the lower tertile.

CONCLUSIONS/INTERPRETATION:

Elevated endotrophin serum levels predict response to two insulin sensitisers and reduce the risk of associated adverse effects, thereby, identifying patients with type 2 diabetes who may profit from PPARγ agonist treatment.

01 Aug 2012·British journal of pharmacologyQ2 · MEDICINE

Submaximal PPARγ activation and endothelial dysfunction: new perspectives for the management of cardiovascular disorders

Q2 · MEDICINE

Review

Author: Pitchai Balakumar ; Sonam Kathuria

PPARγ activation plays an important role in glucose metabolism by enhancing insulin sensitization. PPARγ is a primary target for thiazolidinedione‐structured insulin sensitizers like pioglitazone and rosiglitazone employed for the treatment of type 2 diabetes mellitus. Additionally, PPARγ activation inhibits adhesion cascades and detrimental vascular inflammatory events. Importantly, activation of PPARγ plays a distinctive role in regulating the physiology and expression of endothelial nitric oxide synthase (eNOS) in the endothelium, resulting in enhanced generation of vascular nitric oxide. The PPARγ activation‐mediated vascular anti‐inflammatory and direct endothelial functional regulatory actions could, therefore, be beneficial in improving the vascular function in patients with atherosclerosis and hypertension with or without diabetes mellitus. Despite the disappointing cardiac side effect profile of rosiglitazone‐like PPARγ full agonists, the therapeutic potential of novel pharmacological agents targeting PPARγ submaximally cannot be ruled out. This review discusses the potential regulatory role of PPARγ on eNOS expression and activation in improving the function of vascular endothelium. We argue that partial/submaximal activation of PPARγ could be a major target for vascular endothelial functional improvement. Interestingly, newly synthesized partial agonists of PPARγ such as balaglitazone, MBX‐102, MK‐0533, PAR‐1622, PAM‐1616, KR‐62776 and SPPARγM5 are devoid of or have a reduced tendency to cause the adverse effects associated with full agonists of PPARγ. We propose that the vascular protective properties of pharmacological agents, which submaximally activate PPARγ, should be investigated. Moreover, the therapeutic opportunities of agents that submaximally activate PPARγ in preventing vascular endothelial dysfunction (VED) and VED‐associated cardiovascular disorders are discussed.

100 Deals associated with Balaglitazone

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12781

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 3	DK	Rheoscience Aps	01 Jul 2007

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