A review of berotralstat for the treatment of hereditary angioedema

Farkas, Henriette; Balla, Zsuzsanna

doi:10.1080/1744666x.2023.2150611

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…The stimulation of plasma kallikrein leads to the plasma kallikrein/kinin system activation and enhancement. This activation plays a role in the classical complement cascade pathway, the alternative complement pathway, and blood coagulation 81 – 84 . Nevertheless, no previous reports have documented the anti-cancer properties of berotralstat.…”

Section: Resultsmentioning

confidence: 99%

StackER: a novel SMILES-based stacked approach for the accelerated and efficient discovery of ERα and ERβ antagonists

Schaduangrat,

Homdee,

Shoombuatong

2023

Sci Rep

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The role of estrogen receptors (ERs) in breast cancer is of great importance in both clinical practice and scientific exploration. However, around 15–30% of those affected do not see benefits from the usual treatments owing to the innate resistance mechanisms, while 30–40% will gain resistance through treatments. In order to address this problem and facilitate community-wide efforts, machine learning (ML)-based approaches are considered one of the most cost-effective and large-scale identification methods. Herein, we propose a new SMILES-based stacked approach, termed StackER, for the accelerated and efficient identification of ERα and ERβ inhibitors. In StackER, we first established an up-to-date dataset consisting of 1,996 and 1,207 compounds for ERα and ERβ, respectively. Using the up-to-date dataset, StackER explored a wide range of different SMILES-based feature descriptors and ML algorithms in order to generate probabilistic features (PFs). Finally, the selected PFs derived from the two-step feature selection strategy were used for the development of an efficient stacked model. Both cross-validation and independent tests showed that StackER surpassed several conventional ML classifiers and the existing method in precisely predicting ERα and ERβ inhibitors. Remarkably, StackER achieved MCC values of 0.829–0.847 and 0.712–0.786 in terms of the cross-validation and independent tests, respectively, which were 5.92–8.29 and 1.59–3.45% higher than the existing method. In addition, StackER was applied to determine useful features for being ERα and ERβ inhibitors and identify FDA-approved drugs as potential ERα inhibitors in efforts to facilitate drug repurposing. This innovative stacked method is anticipated to facilitate community-wide efforts in efficiently narrowing down ER inhibitor screening.

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Section: Resultsmentioning

confidence: 99%

StackER: a novel SMILES-based stacked approach for the accelerated and efficient discovery of ERα and ERβ antagonists

Schaduangrat,

Homdee,

Shoombuatong

2023

Sci Rep

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“…Kallikrein produces bradykinin by acting on high-molecular-weight kininogens; therefore, kallikrein inhibitors suppress the subsequent bradykinin-mediated responses. [15] Kallikrein inhibitors berotralstat [20] and lanadelumab [21] are an oral formulation and a subcutaneous formulation with a considerably longer duration of effect, respectively.…”

Section: Discussionmentioning

confidence: 99%

A single-blind, randomized, crossover study on the efficacy of icatibant for sweating-induced dermal pain (icatibant for sweating-induced dermal pain)

et al. 2023

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Introduction: Severe dermal pain triggered by sweating stimuli, such as bathing, exercise, and mental stress, significantly affects patients’ daily lives. The pathomechanism underlying the sweating-induced dermal pain remains poorly understood and there exists no standard treatment for such pain. This study aims to evaluate the effectiveness of icatibant as an analgesic, a bradykinin B2 receptor antagonist, in treating sweating-induced dermal pain, and to establish the role of bradykinin in pain induction. Methods/design: A multicenter, exploratory, crossover, single-blinded, placebo-controlled randomized, comparative study will be conducted to evaluate the efficacy of subcutaneous icatibant injection (30 mg) in treating sweating-induced dermal pain. Ten patients will be enrolled and assigned randomly in a 1:1 ratio to either the icatibant-placebo or placebo-icatibant groups. The primary endpoint is the change in the visual analog scale scores for dermal pain induced by thermal load before and after treatment with icatibant or placebo. Secondary endpoints include changes in the duration of dermal pain, blood and plasma histamine levels, serum angiotensin-converting enzyme levels, and histological evaluation of skin tissue samples at the site of dermal pain. Discussion: The effectiveness of icatibant against sweating-induced dermal pain would provide clear evidence for the involvement of the bradykinin-bradykinin B2 receptor pathway in the pathogenesis of this condition. This finding may contribute to a better understanding of the underlying mechanisms of dermal pain associated with sweating stimuli and has the potential to improve patients’ quality of life by suggesting potential treatment options, specifically, using drugs that inhibit bradykinin or suppress its production.

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“…Osnovni cilj lečenja C1-INH-HAE je da se obezbedi da pacijenti mogu da vode normalan život. Najefikasniji način da se to uradi je da se spreči nastanak napada angioedema [7]. Deklarišući faktori za nastanak HAE su različiti, a izdvaja se: traumatizam (ORL ili stomatološke intervencije), infekcija, fizički napor, neki lekovi npr.…”

Section: Prikaz Slučaja/case Reportunclassified

“…U slučaju gastrointestinalne manifestacije, zabeleženi su slučajevi hirurškog opserviranja i lečenja pacijenata zbog sumnje na akutno abdominalno oboljenje, a klasičnu manifestaciju sa respiratornom simptomatologijom i otocima na licu, lako je zameniti za alergijski, histaminom posredovan angioedem. Uobičajena terapija kortikosteroidima, antihistaminskim lekovima, čak i adrenalinom, u slučaju HAE ne dovodi do otklanjanja simptoma, pa u slučaju akutnog napada neregistrovanog pacijenta možemo faktički samo ugroziti, nehotičnim odlaganjem adekvatnog terapijskog postupka [10,7]. Prva manifestacija oboljenja obično se javlja u detinjstvu, sa edemima koji zahvataju bilo koji deo kože, ali su najčešći na licu i na ekstremitetima.…”

Section: Prikaz Slučaja/case Reportunclassified

A case of angioedema of hereditary origin in a rural clinic near Subotica

Gavrilović,

Momirović-Stojković,

Budimski-Soldat

2023

ABC - čas urg medicine

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Introduction: Hereditary angioedema (HAE) is inherited in an autosomal dominant manner. It manifests with bradykinin-mediated swelling due to a deficiency of C1 inhibitor. Managing these patients is challenging during acute edema and the onset of asphyxiation. Transportation to the hospital takes 25 minutes. Objective: To present a patient with HAE for whom specific therapy has only recently become available. Case Presentation: A female patient presented with difficulty breathing, swelling of the lips, and periorbital edema. Status: visibly distressed, talkative, facial and lip swelling, visible mucosa without edema, uvula and pharynx calm. Respiratory movements symmetric, without the use of accessory muscles. Auscultation revealed normal breath sounds, tachycardic heart action, clear tones without murmurs, and no urticaria. Blood pressure 120/70 mmHg, heart rate 100/min., respiratory rate 30/min., SpO2 98%, capillary refill time (CRT) 2 sec. Treatment: infusion, Methylprednisolone 40 mg IV. She was transported with monitoring. During transport, the condition worsened: blood pressure 105/60 mmHg, heart rate 130/min., respiratory rate 40/min., SpO2 94%, CRT 2 sec. Oxygen at 15 L/min. was initiated, an additional IV line was opened, and capnography showed ETCO2 of 36 mmHg. Methylprednisolone was increased to 80 mg. Preparation for difficult intubation was initiated. Parameters did not worsen, and the patient was transferred to the emergency department of the General Hospital Subotica. Conclusion: Since specific therapies, such as human C1 inhibitor concentrate or bradykinin receptor antagonists, have been approved for self-administration at home during acute attacks, the treatment of these patients has been facilitated, minimizing the potential fatal outcomes and morbidity.

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A review of berotralstat for the treatment of hereditary angioedema

Cited by 6 publications

References 37 publications

StackER: a novel SMILES-based stacked approach for the accelerated and efficient discovery of ERα and ERβ antagonists

StackER: a novel SMILES-based stacked approach for the accelerated and efficient discovery of ERα and ERβ antagonists

A single-blind, randomized, crossover study on the efficacy of icatibant for sweating-induced dermal pain (icatibant for sweating-induced dermal pain)

A case of angioedema of hereditary origin in a rural clinic near Subotica

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