Delving into the Latest Updates on MK-0736 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

11β-HSD

Mechanism

11β-HSD inhibitors(11-beta-hydroxysteroid dehydrogenase inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

AtherosclerosisDiabetes Mellitus, Type 2Hypertension+ [1]

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck GmbH

Merck Sharp & Dohme Corp.

Merck & Co., Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC23H30F3N3O2S

InChIKeyORQZQBUNAMJFCY-UHFFFAOYSA-N

CAS Registry719272-79-4

A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of MK-0736 When Added to Ongoing Therapy With Angiotensin-Converting Enzyme (ACE) Inhibitor or Angiotensin Receptor Blocker (ARB) in Patients With Diabetes and Hypertension - MK-0736 Dose Ranging Study

Start Date18 Dec 2008

Sponsor / Collaborator

Merck & Co., Inc.

NCT00806585

/ TerminatedPhase 2

A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy & Tolerability of MK0736 When Added to Ongoing Therapy With Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) in Patients With T2DM and Hypertension

The study will assess the efficacy and tolerability of MK0736 in patients with Type 2 Diabetes Mellitus and Hypertension who are on ongoing therapy with Angiotensin-Converting Enzyme or Angiotensin Receptor Blocker. After a 3 to 5 week pre-randomization phase, patients will be randomized to either MK0736 (3 doses), placebo, or hydrochlorothiazide (HCTZ). The study will also include a 3 week, posttreatment follow-up period.

Start Date01 Dec 2008

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT00274716

/ CompletedPhase 2

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of MK0736 and MK0916 in Hypertensive Patients

The objective of this study is to evaluate the safety and efficacy of two investigational drugs (MK-0736 and MK-0916) in lowering blood pressure and body weight in patients with hypertension (high blood pressure).
This is an early phase trial and some specific protocol information is proprietary and not publicly available at this time. (Full information is available to trial participants).

Start Date01 Nov 2005

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with MK-0736

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100 Translational Medicine associated with MK-0736

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100 Patents (Medical) associated with MK-0736

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3

Literatures (Medical) associated with MK-0736

01 Jan 2013·MetabolismQ1 · MEDICINE

11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders?

Q1 · MEDICINE

Review

Author: Fotini Adamidou ; Panagiotis Anagnostis ; Marina Kita ; Vasilios G. Athyros ; Niki Katsiki ; Dimitri P. Mikhailidis ; Asterios Karagiannis

OBJECTIVEMetabolic syndrome (MetS) and Cushing's syndrome share common features. It has been proposed that increased glucocorticoid activity at peripheral tissues may play a role in the pathogenesis of MetS and obesity-related disorders. It is well-known that intracellular cortisol concentrations are determined not only by plasma levels but also by the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyzes the conversion of inactive cortisone to active cortisol, especially in the liver and adipose tissue. Another isoenzyme exists, the 11β-hydroxysteroid dehydrogenase type 2, which acts in the opposite direction inactivating cortisol to cortisone in the kidney. This review considers the significance of the 11β-HSD1 inhibition in the treatment of several features of MetS and provides current data about the development of 11β-HSD1 inhibitors, as new agents for this purpose.MATERIALS/METHODSUsing PubMed, we searched for publications during the last 20years regarding the development of 11β-HSD1 inhibitors.RESULTSEmerging data from animal and human studies indicate an association of 11β-HSD1 over-expression with obesity and disorders in glucose and lipid metabolism. This has led to the hypothesis that selective inhibition of 11β-HSD1 could be used to treat MetS and diabetes. Indeed, natural products and older agents such as thiazolidinediones and fibrates seem to exert an inhibitory effect on 11β-HSD1, ameliorating the cardiometabolic profile. In view of this concept, novel compounds, such as adamantyltriazoles, arylsulfonamidothiazoles, anilinothiazolones, BVT2733, INCB-13739, MK-0916 and MK-0736, are currently under investigation and the preliminary findings from both experimental and human studies show a favourable effect on glucose and lipid metabolism, weight reduction and adipokine levels.CONCLUSIONSMany compounds inhibiting 11β-ΗSD1 are under development and preliminary data about their impact on glucose metabolism and obesity-related disorders are encouraging.

01 May 2011·Journal of the American Society of Hypertension

Efficacy and safety of the selective 11β-HSD-1 inhibitors MK-0736 and MK-0916 in overweight and obese patients with hypertension

Article

Author: Kendra Gibson ; Peggy M.T. Hwang ; Gang Jia ; Nicholas W. Ryan ; John Zhang ; Peter U. Feig ; Rae Ann Ruck ; Anne Hermanowski-Vosatka ; Sukrut Shah ; Ronald B. Langdon

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be involved in several abnormalities associated with the metabolic syndrome. This study evaluated the antihypertensive efficacy and safety of two 11β-HSD1 inhibitors, MK-0736 and MK-0916, in overweight-to-obese hypertensive patients. Patients aged 18-75 years with sitting diastolic blood pressure (SiDBP) 90-104 mm Hg, systolic BP <160 mm Hg (after washout of prior antihypertensive medications), and BMI ≥27 to <41 kg/m(2) were randomized to receive 2 or 7 mg/d MK-0736, 6 mg/d MK-0916, or placebo for 12 weeks (n = 51-54/group). Patients with BMI ≥20 to <27 kg/m(2) received 6 mg/d MK-0916 or placebo for 24 weeks (n = 19/group). The primary endpoint was placebo-adjusted change from baseline in trough SiDBP in patients treated for 12 weeks with 7 mg/d MK-0736. The primary endpoint was not met (placebo-adjusted reduction = 2.2 mm Hg; P = .157). With 7 mg/d MK-0736, placebo-adjusted LDL-C decreased by 12.3%, high-density lipoprotein cholesterol by 6.3%, and body weight by 1.4 kg. Both 11β-HSD1 inhibitors were generally well tolerated. In overweight-to-obese patients with hypertension, reduction in SiDBP with MK-0736 was not statistically significant. Nonetheless, MK-0736 was well tolerated and did appear to modestly improve other BP endpoints, LDL-C, and body weight.

01 May 2010·IDrugs : the investigational drugs journal

American Society for Clinical Pharmacology and Therapeutics (ASCPT)-111th annual meeting. 17-20 March 2010, Atlanta, GA, USA.

Author: Veryard, Claire

The 111th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, held in Atlanta, included topics covering disclosures of new data in the field of pharmacokinetics and drug interactions. This conference report highlights selected presentations on pharmacokinetic studies of several investigational drugs, including evatanepag (Pfizer Inc), AEG-33773 (Aegera Therapeutics Inc), JNJ-16269110 (Johnson & Johnson Pharmaceutical Research & Development LLC), PF-3716539 (ViiV Healthcare), MK-0736 (Merck & Co Inc), a combination of Ginkgo biloba and cilostazol (Renexin SK Chemicals Co Ltd), PP-101 (Pacific Pharmaceuticals Co Ltd), ACT-178882 (Acetlion Ltd/Merck & Co Inc) and edoxaban (Daiichi Sankyo Co Ltd).

100 Deals associated with MK-0736

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15209

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	-	Merck Sharp & Dohme Corp.	01 Dec 2008
Hypertension	Phase 2	MX	Merck GmbH	-
Hypertension	Phase 2	ZA	Merck GmbH	-
Hypertension	Phase 2	EU	Merck GmbH	-
Hypertension	Phase 2	PH	Merck GmbH	-
Hypertension	Phase 2	AU	Merck GmbH	-
Hypertension	Phase 2	MY	Merck GmbH	-
Hypertension	Phase 2	US	Merck GmbH	-
Hypertension	Phase 2	PR	Merck GmbH	-
Hypertension	Phase 2	HK	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00274716 (0736-003, CTgov)	Phase 2	Hypertension	249	Placebo+MK0736 (High BMI:MK-0736 2mg→Placebo)	aaoqbhxtho(jzthanqapv) = mfjrdgjxqx cyiroqeutt (odzfpcqfut, fgndhipbau - arbhqhupet) View more	-	14 Feb 2014
				Placebo+MK0736 (High BMI:MK-0736 7mg→Placebo)	aaoqbhxtho(jzthanqapv) = edhwxiphvo cyiroqeutt (odzfpcqfut, msredfsrfb - uxzsbebjmp) View more
NCT00806585 (0736-007, CTgov)	Phase 2	Diabetes Mellitus, Type 2 \| Hypertension	620	MK-0736 (MK-0736 0.5 mg)	zqmxrjqalf(phozkcipbw) = hysjxkeiel efqgahrqgf (ijiifiajin, hmkcsmrklo - jupwvwpuhz) View more	-	11 Dec 2013
				MK-0736 (MK-0736 2.0 mg)	zqmxrjqalf(phozkcipbw) = bammszujdg efqgahrqgf (ijiifiajin, weakyvmgvn - cqcmgpwarw) View more