Delving into the Latest Updates on BQ-788 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

ETB

Mechanism

ETB antagonists(Endothelin receptor type B antagonists)

Therapeutic Areas

Cardiovascular DiseasesNeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

HypertensionMelanoma

Originator Organization

Merck Serono SA

Active Organization-

Inactive Organization

Merck Serono SAMelCure

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC34H51N5O7

InChIKeyLPAHKJMGDSJDRG-DJYQTOCQSA-N

CAS Registry173326-37-9

Patients with vasculitis commonly develop cardiovascular disease. The reasons for this are not clear and is not adequately treated with current drugs. It is thus understand the reasons why patients with vasculitis develop cardiovascular disease in order to develop new drugs to reduced this risk.
Endothelin is a chemical produced by blood vessels that contributes to the development of hypertension and cardiovascular disease Higher than normal levels of endothelin are seen in patients with vasculitis but how this contributes to cardiovascular disease in patients with vasculitis is not clear. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') the investigators can hopefully reduce the risk of cardiovascular disease in patients with vasculitis. The purpose of the study is to ascertain if endothelin receptor antagonists improve blood vessel function in patients with vasculitis.

Start Date01 Aug 2016

Sponsor / Collaborator

The University of Edinburgh

[+1]

100 Clinical Results associated with BQ-788

Login to view more data

100 Translational Medicine associated with BQ-788

Login to view more data

100 Patents (Medical) associated with BQ-788

Login to view more data

989

Literatures (Medical) associated with BQ-788

31 Dec 2024·Blood Pressure

Endothelin-1- and acetylcholine-mediated effects in human and rat vessels: impact of perivascular adipose tissue, diabetes, angiotensin II, and chemerin

Article

Author: Danser, A. H. Jan ; Tan, Lunbo ; Cruz-López, Edwyn O. ; Verdonk, Koen ; Stolk, Daniël G. ; van den Bogaerdt, Antoon J.

OBJECTIVETo study the role of perivascular adipose tissue (PVAT) in the reactivity of rat and human vessels.METHODSIliac and mesenteric arteries were obtained from normotensive Sprague-Dawley rats, hypertensive transgenic (mRen2)27 rats overexpressing mouse renin, and (mRen2)27 rats made diabetic with streptozotocin. Human coronary arteries were obtained from donors. Concentration-response curves were constructed to endothelin-1 and acetylcholine with and without PVAT. The contribution of NO and endothelium-dependent hyperpolarization (EDH) were determined making use of the NO synthase inhibitor L-NAME and the EDH inhibitors apamin + TRAM-34. The endothelin type A and type B (ET_A, ET_B) receptor blockers BQ123 and BQ788, the chemerin inhibitors α-NETA and pravastatin, and the angiotensin receptor blocker losartan were also used.RESULTSIn rat iliac arteries, PVAT diminished endothelin-induced constriction, while the opposite was true in human coronaries. Coronary effects were unaltered by α-NETA, pravastatin, or losartan. ET_B receptor-mediated relaxation in iliac arteries occurred only with PVAT, and BQ123 blocked endothelin-1-induced constriction. Diabetes upregulated the anticontractile effects of PVAT. In rat mesenteric arteries, acetylcholine-induced relaxation with PVAT relied on NO, and on NO + EDH without PVAT. Diabetes upregulated the EDH component exclusively with PVAT.CONCLUSIONPVAT modulates ET-1-induced constriction in a vessel type-dependent manner. Its enhancing effects in coronaries involved neither chemerin nor angiotensin II. Its anticontractile effects in rat iliac arteries involved ET_B receptor-mediated relaxation. Diabetes upregulated PVAT's anticontractile effects. In mesenteric arteries, PVAT counterbalanced the EDH component of the relaxant effect of acetylcholine. Diabetes reversed this effect by upregulating the EDH component.

06 Nov 2024·Clinical Science

Complex regulation of tau phosphorylation by the endothelin system in brain microvascular endothelial cells (BMVECs): link to barrier function

Article

Author: Ergul, Adviye ; Jamil, Sarah ; Abdul, Yasir ; Albayram, Onder ; Edwards, Jazlyn ; Karakaya, Eda

AbstractEndothelin-1 (ET-1), the most potent vasoconstrictor identified to date, contributes to cerebrovascular dysfunction. ET-1 levels in postmortem brain specimens from individuals diagnosed with Alzheimer’s disease (AD) and related dementias (ADRD) were shown to be related to cerebral hypoxia and disease severity. ET-1-mediated vascular dysfunction and ensuing cognitive deficits have also been reported in experimental models of AD and ADRD. Moreover, studies also showed that ET-1 secreted from brain microvascular endothelial cells (BMVECs) can affect neurovascular unit integrity in an autocrine and paracrine manner. Vascular contributions to cognitive impairment and dementia (VCID) is a leading ADRD cause known to be free of neuronal tau pathology, a hallmark of AD. However, a recent study reported cytotoxic hyperphosphorylated tau (p-tau) accumulation, which fails to bind or stabilize microtubules in BMVECs in VCID. Thus, the study aimed to determine the impact of ET-1 on tau pathology, microtubule organization, and barrier function in BMVECs. Cells were stimulated with 1 μM ET-1 for 24 h in the presence/absence of ETA (BQ123; 20 μM) or ETB (BQ788; 20 μM) receptor antagonists. Cell lysates were assayed for an array of phosphorylation site-specific antibodies and microtubule organization/stabilization markers. ET-1 stimulation increased p-tau Thr231 but decreased p-tau Ser199, Ser262, Ser396, and Ser214 levels only in the presence of ETA or ETB antagonism. ET-1 also impaired barrier function in the presence of ETA antagonism. These novel findings suggest that (1) dysregulation of endothelial tau phosphorylation may contribute to cerebral microvascular dysfunction and (2) the ET system may be an early intervention target to prevent hyperphosphorylated tau-mediated disruption of BMVEC barrier function.

01 Sep 2024·Journal of Neuroimmunology

Sexual dimorphism of hypothalamic serotonin release during systemic inflammation: Role of endothelin-1

Article

Author: Costa, Regina Azevedo ; Stern, Cristina Aparecida Jark ; de Oliveira Guaita, Gisele ; Zampronio, Aleksander Roberto ; Branco, Luiz Guilherme Siqueira ; Amatnecks, Jefferson Angulski

The hypothalamus receives serotonergic projections from the raphe nucleus in a sex-specific manner. During systemic inflammation, hypothalamic levels of serotonin (5-hydroxytryptamine [5-HT]) decrease in male rats. The present study evaluated the involvement of endothelin-1 (ET-1) in the febrile response, hypolocomotion, and changes in hypothalamic 5-HT levels during systemic inflammation in male and female rats. An intraperitoneal injection of lipopolysaccharide (LPS) induced a febrile response and hypolocomotion in both male and female rats. However, although LPS reduced hypothalamic levels of 5-HT and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in male rats, it increased these levels in female rats. An intracerebroventricular injection of the endothelin-B receptor antagonist BQ788 significantly reduced LPS-induced fever and hypolocomotion and changes in hypothalamic 5-HT and 5-HIAA levels in both male and female rats. The i.c.v. administration of ET-1 induced a significant fever and hypolocomotion, but reduced the hypothalamic levels of 5-HT and 5-HIAA in both males and females. These results suggest an important sexual dimorphism during systemic inflammation regarding the release of 5-HT in the hypothalamus. Moreover, ET-1 arises as an important mediator involved in the changes in hypothalamic 5-HT levels in both male and female rats.

100 Deals associated with BQ-788

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	BQ-788	-	-

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Phase 2	-	MelCure	01 May 2011
Hypertension	Phase 2	-	Merck Serono SA	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01395329 (NETS, CTgov)	Phase 4	Hypertension \| Prehypertension	42	FBF response to Sodium Nitroprusside+Nebivolol+ACh+BQ-788+BQ-123 (Nebivolol)	vydxsauaov(xgywdskuaj) = vivkmfwcsr zphhacokxy (oozmillpyt, trubdqbhgp - iitizblgtk) View more	-	06 Dec 2018
NCT01395329 (NETS, CTgov)	Phase 4	Hypertension \| Prehypertension	42	FBF response to Sodium Nitroprusside+Metoprolol+ACh+BQ-788+BQ-123 (Metoprolol)	vydxsauaov(xgywdskuaj) = lkrvnrpiha zphhacokxy (oozmillpyt, dvdxupotxt - sgtvqydwnz) View more	-	06 Dec 2018
NCT02442466 (Pubmed \| Oncologist) Manual	Phase 1	Melanoma	5	BQ788	(jzhitwtrua) = iyuarwldsn einbcowdyr (yckiqqeryn )	Positive	01 Oct 2015