PDE4 inhibitors(Phosphodieterase 4 inhibitors), TGF-β1 inhibitors(Transforming growth factor beta 1 inhibitors), TNF inhibitors(Tumor necrosis factor inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication

Glomerulonephritis

Inactive Indication-

Originator Organization

Tsumura & Co.

Active Organization

Hokkaido University

Tsumura & Co.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC19H20N2O4

InChIKeyVNHQNKMWLMQDLQ-RMKNXTFCSA-N

CAS Registry637773-88-7

100 Clinical Results associated with TJN-598

100 Translational Medicine associated with TJN-598

100 Patents (Medical) associated with TJN-598

Literatures (Medical) associated with TJN-598

01 Feb 2011·Clinical and Experimental NephrologyQ3 · MEDICINE

Effects of TJN-598, a new selective phosphodiesterase type IV inhibitor on anti-Thy1 nephritis in rats

Q3 · MEDICINE

Article

Author: Hirobumi Maruyama ; Tomohisa Hattori ; Yoshio Kase ; Shuichi Takeda ; Hiroshi Takeda ; Yoshihiro Hasegawa ; Chiharu Sadakane ; Shoichiro Shindo ; Junichi Koseki

BACKGROUNDPhosphodiesterase type IV (PDEIV) plays an important role in the immune response and inflammation. However, it is well known that classical PDEIV inhibitors have systemic side effects, so the clinical and chronic use of these agents as therapy for glomerulonephritis is difficult. This study was performed to elucidate the anti-nephritic effects of TJN-598, a new chemical compound derived from herbal components, on experimental mesangial proliferative glomerulonephritis.METHODSWe first examined the effects of TJN-598 and captopril on mesangial expansion induced by anti-Thy1 serum in rats. Second, to investigate the effects of TJN-598 and rolipram, which are typical PDEIV inhibitors, on the production of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1, glomeruli were isolated from rats with anti-Thy1 nephritis and incubated with the test drugs in vitro for 48 h.RESULTSTreatment with TJN-598 prevented an increase in the mesangial area/total glomerular area, in the number of cells in the glomerular cross section and matrix index. TJN-598 also inhibited the increases in the expression of α-smooth muscle actin, the TGF-β1-positive area, in the number of ED-1 positive cells and proliferating cell nuclear antigen-positive cells in the glomeruli. Furthermore, administration of TJN-598 inhibited increases in the levels of TGF-β1 protein derived from glomeruli with anti-Thy-1 nephritis. The addition of both TJN-598 and rolipram to the culture supernatant inhibited both increased expression of TGF-β1 and increases in levels of TNF-α in glomeruli isolated from rats with anti-Thy1 nephritis in a dose-dependent manner.CONCLUSIONThese results suggest that TJN-598, a PDEIV inhibitor, is effective against expansion of mesangial cells, via the suppression of secretion of TGF-β1 and TNF-α from inflamed glomeruli.

100 Deals associated with TJN-598

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Glomerulonephritis	Phase 2	-	Tsumura & Co.	-
Glomerulonephritis	Phase 2	JP	-	-

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TJN-598

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