Delving into the Latest Updates on NO-Ursodeoxycholic Acid with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

,no-udca, NO-ursodiol

+ [2]

Target

caspase 3 x caspase 8 x caspase 9

Action

inhibitors

Mechanism

caspase 3 inhibitors(Caspase-3 inhibitors), caspase 8 inhibitors(Caspase-8 inhibitors), caspase 9 inhibitors(Caspase-9 inhibitors)

Therapeutic Areas

Digestive System Disorders

Active Indication-

Inactive Indication

Hypertension, Portal

Originator Organization

Nicox SA

Active Organization-

Inactive Organization

Nicox SAForest Laboratories, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC38H55NO10

InChIKeyWTAVOESJEWSDJC-DNVPPMEBSA-N

CAS Registry301828-26-2

AbstractBackgroundUrsodeoxycholic acid (UDCA), statins, and ezetimibe (EZE) have demonstrated beneficial effects against non-alcoholic fatty liver disease (NAFLD). We investigated the efficacy of the combination of UDCA and the mix of rosuvastatin (RSV)/EZE in the treatment of NAFLD.MethodsNAFLD mouse models were developed by injecting thioacetamide, fasting, and high-carbohydrate refeeding, high-fat diet, and choline-deficient L-amino acid-defined high-fat diet (CDAHFD). Low-dose UDCA (L-UDCA; 15 mg/kg) or high-dose UDCA (H-UDCA; 30 mg/kg) was administered with RSV/EZE. We also employed an in vitro model of NAFLD developed using palmitic acid-treated Hepa1c1c7 cells.ResultsCo-administration of RSV/EZE with UDCA significantly decreased the collagen accumulation, serum alanine aminotransferase (ALT) levels, and mRNA levels of fibrosis-related markers than those observed in the vehicle group in thioacetamide-treated mice (all P < 0.01). In addition, in the group fasted and refed with a high-carbohydrate diet, UDCA/RSV/EZE treatment decreased the number of apoptotic cells and serum ALT levels compared with those observed in the vehicle group (all P < 0.05). Subsequently, H-UDCA/RSV/EZE treatment decreased the number of ballooned hepatocytes and stearoyl-CoA desaturase 1 (SCD-1) mRNA levels (P = 0.027) in the liver of high-fat diet-fed mice compared with those observed in the vehicle group. In the CDAHFD-fed mouse model, UDCA/RSV/EZE significantly attenuated collagen accumulation and fibrosis-related markers compared to those observed in the vehicle group (all P < 0.05). In addition, UDCA/RSV/EZE treatment significantly restored cell survival and decreased the protein levels of apoptosis-related markers compared to RSV/EZE treatment in palmitic acid-treated Hepa1c1c7 cells (all P < 0.05).ConclusionCombination therapy involving UDCA and RSV/EZE may be a novel strategy for potent inhibition of NAFLD progression.

01 Jan 2011·International Journal of Hepatology

NCX 1000 Alone or in Combination with Vitamin E Reverses Experimental Nonalcoholic Steatohepatitis in the Rat Similarly to UDCA

Article

Author: Brault, Antoine ; Vallerand, Diane ; Haddad, Yara ; Haddad, Pierre S. ; Spénard, Jean

We explored the therapeutic effect of NCX 1000, a derivative of ursodeoxycholic acid (UDCA) with nitric oxide (NO) donating properties, alone or in combination with vitamin E, in an experimental model of NASH in the rat.Methods. A control group was fed a standard liquid diet (Control), and the NASH groups were fed a high-fat liquid diet for 12 weeks without (NASH) or with simultaneous daily gavage with either NCX 1000 at 15 or 30 mg/kg (N15 and N30, resp.), or N15 plus vitamin E 100 mg/kg (N15 + VitE) for the last 6 weeks; UDCA 17.2 mg/kg was used as a reference.Results. NASH rats developed all key features of the disease. Treatments with N30 improved liver histology, decreased lipid peroxidation, and completely suppressed increases in LDH release, plasma insulin, and TNF-α. It also decreasedO2∙-release and returned liver weight and glutathione back to normal. All effects were similar to the reference treatment, UDCA. The N15 treatment was less efficient than the N30 group, but became comparable to the latter when combined to vitamin E.Conclusion. Our study demonstrates that NCX 1000 has potent cytoprotective, antioxidant, and hypoinsulinemic properties that can be enhanced by combination with vitamin E.

01 Dec 2010·Yao xue xue bao = Acta pharmaceutica Sinica

[Synthesis and biological evaluation of nitrate-oleanolic acid hybrids as inhibitors of HepG2 cell apoptosis].

Article

Author: Chen, Li ; Shang, Juan ; Zhang, Yi-hu ; Tian, Ji-de ; Wang, Zhi-feng

To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.

100 Deals associated with NO-Ursodeoxycholic Acid

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External Link

KEGG	Wiki	ATC	Drug Bank
-	NO-Ursodeoxycholic Acid	-	DB16026

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension, Portal	Phase 2	Spain	Forest Laboratories, Inc.	01 Nov 2005

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


PANURSO STUDY (UEGW2021)	Not Applicable	Pancreatitis	422	UDCA	exxchmvped(vpttyduflc) = kmjuwxkdwr pllyczoetz (fgvmcrvrzw, 660 - 790) View more	Positive	02 Oct 2021
				No UDCA	exxchmvped(vpttyduflc) = umabamhsju pllyczoetz (fgvmcrvrzw, 525 - 664)
EHA2017	Not Applicable	Thrombotic Microangiopathies	671	Ursodeoxycholic acid	ehhxpxcqin(fumetiaabp) = ufhavianzu ljflpxhglq (ivmpuormyz, 5.9 - 14.3)	-	18 May 2017
				Non-ursodeoxycholic acid	ehhxpxcqin(fumetiaabp) = qbuvvszjfi ljflpxhglq (ivmpuormyz, 11.7 - 18.1)