Delving into the Latest Updates on PG-116800 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [1]

Target

MMPs

Mechanism

MMPs inhibitors(Matrix metalloproteinase inhibitors)

Therapeutic Areas

Immune System DiseasesCardiovascular DiseasesSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

CardiomegalyHeart FailureMyocardial Infarction+ [1]

Originator Organization

Procter & Gamble Co.

Active Organization-

Inactive Organization

Procter & Gamble, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC24H27N3O7S

InChIKeyJAYVKNDQKXUNOJ-UHFFFAOYSA-N

CAS Registry291533-11-4

Contemporary treatments for osteoarthritis (OA) pursue only to alleviate the pain caused by the illness. Discovering disease-modifying osteoarthritis drugs (DMOADs) that can induce the repair and regeneration of articular tissues would be of substantial usefulness. The purpose of this manuscript is to review the contemporary role of DMOADs in managing OA. A narrative literature review on the subject, exploring the Cochrane Library and PubMed (MEDLINE) was performed. It was encountered that many publications have analyzed the impact of several DMOAD methods, including anti-cytokine therapy (tanezumab, AMG 108, adalimumab, etanercept, anakinra), enzyme inhibitors (M6495, doxycycline, cindunistat, PG-116800), growth factors (bone morphogenetic protein-7, sprifermin), gene therapy (micro ribonucleic acids, antisense oligonucleotides), peptides (calcitonin) and others (SM04690, senolitic, transient receptor potential vanilloid 4, neural EGFL-like 1, TPCA-1, tofacitinib, lorecivivint and quercitrin). Tanezumab has been demonstrated to alleviate hip and knee pain in individuals with OA but can cause major adverse events (osteonecrosis of the knee, rapid illness progression, augmented prevalence of total joint arthroplasty of involved joints, particularly when tanezumab is combined with nonsteroidal anti-inflammatory drugs. SM04690 (a Wnt inhibitor) has been demonstrated to be safe and efficacious in alleviating pain and ameliorating function as measured by the Western Ontario and McMaster Universities Arthritis Index. The intraarticular injection of lorecivivint is deemed safe and well tolerated, with no important reported systemic complications. In conclusion, even though DMOADs seem promising, their clinical effectiveness has not yet been demonstrated for managing OA. Until forthcoming studies can proved the medications' capacity to repair and regenerate tissues affected by OA, physicians should keep using treatments that only intend to alleviate pain.

01 Nov 2008·Journal of Cardiac FailureQ2 · MEDICINE

Matrix Metalloproteinase Inhibition Attenuates Atrial Remodeling and Vulnerability to Atrial Fibrillation in a Canine Model of Heart Failure

Q2 · MEDICINE

Article

Author: Xudong Hu ; Gordon W. Moe ; Liia Doumanovskaia ; Gabriel Laurent ; Paul Dorian ; Andrea Konig

BACKGROUNDAtrial structural remodeling occurs in evolving heart failure (HF) and is an important substrate for the development of atrial fibrillation (AF). The matrix metalloproteinases (MMPs) play a role in extracellular remodeling, and recent studies have demonstrated increased atrial MMP activity in HF. Whether increased MMP activity directly contributes to atrial remodeling and AF in the setting of HF remains unclear. The current study examined the effects of MMP inhibition on atrial structural remodeling and AF vulnerability during HF progression.METHODS AND RESULTSThree groups of dogs (n = 5 each)--control normal dogs (controls) and 10 dogs subjected to simultaneous atrioventricular pacing (SAVP) for 2 weeks to induce HF and randomly assigned to treatment with placebo (SAVP-placebo) or a MMP inhibitor PGE-7113313, a MMP-1-sparing MMP inhibitor, 6 mg/kg orally twice daily (SAVP-MMPi)--were studied. SAVP-MMPi dogs had less AF inducibility (percent of burst attempts leading to AF episodes: 1.7 +/- 2.9 seconds vs. 23+/-19 seconds, mean +/- SD, P < .05) and maintenance (AF duration: 253 [105 to 326] vs. 1932 [1296 to 2724] seconds, median [25th-75th quartile], P < .05) than SAVP-placebo dogs. The SAVP-MMPi dogs had significantly smaller increases in atrial myocyte cross sectional area, collagen area fraction, and MMP-9 activity relative to controls than SAVP-placebo. There were, however, no significant differences in the changes in chamber dimension and function in the left atrium.CONCLUSIONSThis unique finding of an attenuation of the vulnerability to AF in conjunction with reduced myocyte hypertrophy and fibrosis after MMP inhibition suggests that heightened MMP activity in the atria contributes to atrial structural remodeling and AF promotion during evolving HF.

01 Jan 2007·Arthritis Research & TherapyQ2 · MEDICINE

The quest for the Holy Grail: a disease-modifying osteoarthritis drug

Q2 · MEDICINE

OA

Author: Francis Berenbaum

The unfortunate story of the matrix metalloproteinase inhibitor PG116800, which had no effect on the osteoarthritic process but had unexpected side effects, highlights the following. First, reality does not always match the theory. Second, cell biology data must be interpreted within the context of a specific environment. Third, the specificity of an enzyme inhibitor is always relative. Finally, a critical evaluation of the benefit/risk ratio of a drug must be carefully conducted and checked before and after launch. Well designed post-marketing surveillance is mandatory.

100 Deals associated with PG-116800

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05495

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cardiomegaly	Phase 2	US	Procter & Gamble, Inc.	01 Sep 2003
Cardiomegaly	Phase 2	PL	Procter & Gamble, Inc.	01 Sep 2003
Cardiomegaly	Phase 2	CA	Procter & Gamble, Inc.	01 Sep 2003
Heart Failure	Phase 2	CA	Procter & Gamble, Inc.	01 Sep 2003
Heart Failure	Phase 2	PL	Procter & Gamble, Inc.	01 Sep 2003
Myocardial Infarction	Phase 2	US	Procter & Gamble, Inc.	01 Sep 2003
Myocardial Infarction	Phase 2	PL	Procter & Gamble, Inc.	01 Sep 2003
Myocardial Infarction	Phase 2	CA	Procter & Gamble, Inc.	01 Sep 2003
Osteoarthritis, Knee	Phase 2	GB	Procter & Gamble, Inc.	01 Jul 2002
Osteoarthritis, Knee	Phase 2	HU	Procter & Gamble, Inc.	01 Jul 2002

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00041756 (CTgov)	Phase 2	Osteoarthritis, Knee	395	PG-530742 (25 mg PG-530742)	exyzuvodsc(dtgqrpyagd) = rtuhjhmwja lqusdarlyu (txiuktftfu, skcwbfwvjn - ooyxzydhpa) View more	-	08 Nov 2011
NCT00041756 (CTgov)	Phase 2	Osteoarthritis, Knee	395	50 mg PG-530742 (50 mg PG-530742)	exyzuvodsc(dtgqrpyagd) = xrvibjeckb lqusdarlyu (txiuktftfu, uftfddutsd - suasrnxuif) View more	-	08 Nov 2011
NCT00067236 (CTgov)	Phase 2	Myocardial Infarction \| Cardiomegaly \| Heart Failure	253	PG-116800 (given as PG-530742)	jrsqppuuue(qpmurnofbt) = aagkhhftqu inakzxlkir (tzgmrqfpjk, afymriiysm - pyyymelilu) View more	-	04 Nov 2011