Measurement and cardiovascular relevance of partial agonist activity (PAA) involving β1- and β2-adrenoceptors

Cruickshank, J. M.

doi:10.1016/0163-7258(90)90093-h

Cited by 11 publications

(3 citation statements)

References 321 publications

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“…Syrosingopine, used as an anti-hypertensive drug for over 40 years [ 19 ], has recently revealed its potential in cancer treatment. Don Benjamin et al first reported the synthetic lethality effect of syrosingopine combined with metformin in granulocytic leukemia, sarcoma, and multiple myeloma, providing crucial clues for subsequent antitumor studies [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response

Li,

Song,

Shi

et al. 2024

Cell Death Dis

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Non-small cell lung cancer (NSCLC) presents a global health challenge due to its low five-year survival rates, underscoring the need for novel therapeutic strategies. Our research explored the synergistic mechanisms of syrosingopine and UK-5099 in treating NSCLC. In vitro experiments showed that the combination of syrosingopine and UK-5099 significantly synergized to suppress NSCLC proliferation. Further experiments revealed that this combination induced cell cycle arrest and promoted apoptosis in NSCLC cells. In vivo experiments demonstrated that the combination of syrosingopine and UK-5099 markedly inhibited tumor growth. Mechanistic studies revealed that this drug combination promoted mitochondrial damage by inducing lactate accumulation and oxidative stress. Additionally, the combination triggered an integrated stress response (ISR) through the activation of heme-regulated inhibitor kinase (HRI). Importantly, our findings suggested that the synergistic suppression of NSCLC by syrosingopine and UK-5099 was dependent on ISR activation. In summary, our study proposed a promising therapeutic approach that involved the combination of Syrosingopine and UK-5099 to activate ISR, significantly hindering NSCLC growth and proliferation.

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Section: Discussionmentioning

confidence: 99%

Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response

Li,

Song,

Shi

et al. 2024

Cell Death Dis

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“…An important difference is observed between betas-selective blockers with moderate (epanolol) or high (xamoterol) beta 1 partial agonism. The latter drug does not lower blood pressure and the former causes only a minimal, i.e., 6/4 mmHg, fall in blood pressure [35]. Furthermore prenalterol, a nonselective agent with partial agonist activity equivalent to xamoterol, does not reduce blood pressure either.…”

Section: Central and Peripheral Hemodynamicsmentioning

confidence: 92%

“…For example, a recent review of the potential benefits of beta blockers with partial agonism concludes that with: "The beta blockers with a higher level of ISA, such as pindolol, blood pressure falls in parallel with a reduction in total peripheral resistance to below the pre-treatment level" [33]. This statement is true for pindolol but not true for epanolol, which, although having only slightly less PAA than pindolol, has minimal effects on blood pressure, presumably because the partial agonism is beta I selective [35]. Another reviewer concludes, "In no instance has I.S.A.…”

Section: Concepts and Detinitionsmentioning

confidence: 94%

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes

Jd¹

1991

Cardiovasc Drug Ther

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Despite the fact that beta blockers were introduced into clinical practice 25 years ago, new beta blockers with differing kinetic and dynamic profiles continue to be developed and marketed. This overview assesses some of the more extensively studied agents from the point of view of proof of utility and the validity of claims for therapeutic advances. The clinical data suggests that despite the expectations of improvements based on kinetic and dynamic consideration, none of the newer agents have been shown unequivocally, either in terms of efficiency or tolerability, to be an advance over the reference agents, the beta 1 antagonists atenolol and metoprolol. This may be either because such improvements will not occur or because of shortcomings in the design and duration of comparative studies. There are trends to suggest that celiprolol has lesser effects on bronchial function and that it has a lesser impact on lipoprotein profiles. Approaches are suggested that might enable clinicians to appraise for themselves the validity of claims for the improved efficiency of new beta blockers.

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Beta-Adrenergic Blockers

Frishman¹,

Cheng-Lai²,

Chen³

2000

Current Cardiovascular Drugs

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Measurement and cardiovascular relevance of partial agonist activity (PAA) involving β1- and β2-adrenoceptors

Cited by 11 publications

References 321 publications

Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response

Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes

Beta-Adrenergic Blockers

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