Delving into the Latest Updates on BQ-788 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BQ 788, BQ-788, BQ788

Target

ETB

Action

antagonists

Mechanism

ETB antagonists(Endothelin receptor type B antagonists)

Therapeutic Areas

Cardiovascular DiseasesNeoplasmsSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

HypertensionMetastatic melanoma

Originator Organization

Merck Serono SA

Active Organization-

Inactive Organization

Merck Serono SAMelcure SA (Switzerland)

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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

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100 Translational Medicine associated with BQ-788

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100 Patents (Medical) associated with BQ-788

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836

Literatures (Medical) associated with BQ-788

01 Aug 2026·BIOCHEMICAL PHARMACOLOGY

Bosentan confers cardioprotection against cisplatin toxicity: Involvement of β-arrestin-linked ETA receptor signaling

Article

Author: Mangmool, Supachoke ; Khine, Hnin Ei Ei ; Parichatikanond, Warisara

The endothelin system, primarily through activation of the endothelin A (ET_A) receptor, mediates vasoconstriction and triggers inflammatory and proliferative responses, positioning it as a key mediator and promising therapeutic target in cardiovascular injury. Bosentan, a dual ET_A/ET_B receptor antagonist, has been reported to act as a biased ligand at the ET_A receptor. This study investigated whether bosentan protects H9c2 cardiomyoblasts against cisplatin-induced cardiotoxicity by preferentially modulating β-arrestin-related signaling of ET_A receptor. Bosentan treatment suppressed cellular injury by attenuating reactive oxygen species (ROS) production, early apoptosis, and caspase-3/7 activity following cisplatin exposure. Bosentan preserved mitochondrial function by improving cellular respiration and glycolysis, as well as upregulating mitochondrial regulators OPA1 and ATP5A and anti-apoptotic BCL2, while downregulating mitochondrial fission-related DNM1 and pro-apoptotic BAX. Co-treatment with endothelin-1 (ET-1) synergistically aggravated cisplatin-induced cellular injury and diminished bosentan-mediated cardioprotection, supporting the involvement of ET receptors. ET_A receptor blockade (BQ-123) enhanced bosentan-mediated protection more effectively than ET_B receptor inhibition (BQ-788), suggesting ET_A receptor dominance. Inhibition of β-arrestin (barbadin) reduced bosentan's efficacy to a greater extent than G_αq protein inhibition (FR900359), highlighting a greater contribution of β-arrestin-mediated pathways. In addition, ERK1/2 and PI3K/AKT inhibition each impaired bosentan-enhanced pro-survival response, indicating the parallel involvement of both survival cascades. Although bosentan antagonizes both ET_A and ET_B receptors and modulates β-arrestin and G_αq signaling, its protective effect appears primarily mediated by ET_A receptor antagonism and β-arrestin-linked pro-survival signaling. This potential mechanism of bosentan may provide a basis for further investigation into therapeutic strategies for chemotherapy-induced cardiotoxicity.

01 May 2026·JOURNAL OF BIOLOGICAL CHEMISTRY

Endothelin-1 induces Zfp36 family RNA-binding proteins and restrains cytokine and chemokine production in reactive astrocytes

Article

Author: Koyama, Yutaka ; Michinaga, Shotaro ; Izumi, Yasuhiko ; Takahashi, Nagi ; Izumikawa, Eri ; Hamada, Chisato ; Nishiuma, Aina ; Hishinuma, Shigeru

Zinc-finger protein 36 (Zfp36) family RNA-binding proteins, such as tristetraprolin (TTP/Zfp36), butyrate response factor (BRF)-1/Zfp36L1, and BRF-2/Zfp36L2, regulate the expression of cytokine/chemokine mRNA with AU-rich elements. In traumatic brain injury (TBI), reactive astrocytes produce various cytokines and chemokines that induce neuroinflammation. However, despite their importance in neuroinflammation, little is known about the regulation of cytokine and chemokine production by the Zfp36 family proteins in astrocytes. Endothelin-1 (ET-1), which promotes the conversion to reactive astrocytes, stimulates astrocytic cytokine and chemokine production. In the present study, we examined the effects of ET-1 on Zfp36 family protein expression in astrocytes and the roles of these proteins in cytokine/chemokine production. ET-1 (100 nM) increased the expression of TTP and BRF-1 in cultured astrocytes. In a mouse model of TBI, expression of TTP and BRF-1 increased, which was reduced by intracerebroventricular administration of BQ788, an ET_B antagonist. Immunohistochemical analyses showed that TTP and BRF-1 were present in reactive astrocytes. Knockdown of TTP by siRNA enhanced the production of ET-induced CCL2 and IL-6 in cultured astrocytes, while BRF-1 knockdown enhanced the CCL2, CXCL1, and CX3CL1 production. RNA immunoprecipitation/PCR analyses showed that ET-1 stimulated TTP binding to CCL2 and IL-6 mRNAs, and BRF-1 binding to CCL2, CXCL1, and CX3CL1 mRNAs. These results suggest that ET-1 stimulates the induction of TTP and BRF-1 in astrocytes and that the production of some astrocytic chemokine/cytokine is negatively regulated by the increments in TTP and BRF-1 production.

01 Mar 2026·Journal of Orthopaedic Translation

Endothelin-1/endothelin B receptor signalling mediates Prx1+ skeletal stem cells senescence: A driver of osteoporotic bone loss

Article

Author: Zou, Zhou ; Gong, Weiyuan ; Wen, Chunyi ; Lu, Xuan ; Lin, Junxin ; Zhang, Yuqi ; Au, Manting ; Ouyang, Hongwei ; Xiao, Guozhi ; Tang, Bin

Background:

Stem cells residing in the perivascular niche are critical for skeletal homeostasis. Vascular endothelin-1 (ET-1) controls stem cell fate in development, but its role in the exhaustion of skeletal stem cells (SSCs) and subsequent bone degeneration in osteoporosis remains poorly understood. This study aimed to determine whether ET-1 signalling drives SSCs senescence and to elucidate the underlying mechanisms.

Methods:

We utilised a combination of human single-cell RNA sequencing datasets, murine models of ageing and ovariectomy (OVX), and an endothelial-specific ET-1 overexpression transgenic (TET-1) mouse model. In vitro studies on mesenchymal stem cells (MSCs) employed ET-1 challenge with and without receptor-specific antagonists (BQ123 for ET_AR, BQ788 for ET_BR). The mechanism was further probed using transcriptomic profiling and validated in vivo through Prx1⁺ SSCs-specific ET_BR knockout (Prx1-Cre;ET_BR ^fl/fl ) and pharmacological inhibition with the ET_BR antagonist BQ788.

Results:

In aged and OVX mice, ET_BR expression was significantly upregulated in SSCs concurrent with bone loss. Transgenic ET-1 overexpression recapitulated an aged bone phenotype, inducing SSCs senescence and accelerating bone loss. In vitro, ET-1 triggered MSCs senescence and reactive oxygen species (ROS) accumulation. Such effects were specifically abrogated by ET_BR, but not ET_AR. Transcriptomic analysis revealed that ET-1/ET_BR signalling synergistically dysregulates the PI3K-AKT and p53 pathways to orchestrate senescence. Critically, both genetic knockout of ET_BR in Prx1⁺ SSCs and pharmacological inhibition with BQ788 mitigated oxidative stress, reduced cellular senescence, and preserved bone mass in OVX and aged mice.

Conclusion:

This study identified the ET-1/ET_BR signalling axis as a critical driver of osteoporosis by promoting ROS-mediated SSCs senescence. We established a link between vascular ageing and skeletal decline.

The translational potential of this article:

This study positioned ET_BR blockade as a promising novel therapeutic strategy for osteoporosis. By targeting the upstream driver of SSCs exhaustion, ET_BR inhibition offers a potential paradigm shift from palliative care to proactive rejuvenation of the osteogenic niche. This approach could counteract both postmenopausal and age-related bone loss by restoring the bone-forming potential of the skeleton, addressing a significant unmet clinical need.

100 Deals associated with BQ-788

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hypertension	Phase 2	-	Merck Serono SA	-
Metastatic melanoma	Phase 1	-	Melcure SA (Switzerland)	01 May 2011

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Clinical Result

Indication

Phase

Evaluation

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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)	ujcpknpyhk(rvliurdfhu) = fuwvqkvgni ulrrksqkkb (swgarplvwy, ozvywynqba - zfzkuvqrlq) 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)	ujcpknpyhk(rvliurdfhu) = jhhgyrazww ulrrksqkkb (swgarplvwy, hpaobvbaql - qayybsvjyp) View more	-	06 Dec 2018
NCT02442466 (Pubmed \| Oncologist) Manual	Phase 1	Melanoma	5	BQ788	ayoarasnml(mxcvwqsnak) = pbrmhbuovm qzbncvjnah (jptjbcejyp )	Positive	01 Oct 2015