Author: Gorup, Luiz Fernando ; de Castilho Alves Morais, Elizângela Maria ; Figueiredo, Eduardo Costa ; Arnoni, Estela Domingos ; Rosa, Mariana Azevedo ; Moreira, Ailton José ; Mendes, Tássia Venga

Magnetic particle spray mass spectrometry (MPS-MS), an innovative ambient ionization technique proposed by our research group, was employed to determine beta-blockers in human plasma samples. A dispersive solid phase extraction of atenolol, metoprolol, labetalol, propranolol, nadolol, and pindolol was carried out using magnetic molecularly imprinted polymer (M-MIP) particles that were attached to the tip of a metal probe, which was placed in the mass spectrometer inlet. A solvent (1% formic acid in methanol) was dispensed on the particles, and the Taylor cone was formed around them (in high voltage). The analytes were desorbed/ionized and determined by a triple quadrupole mass spectrometer. M-MIP was synthesized with oxprenolol as a pseudo-template, demonstrating good selectivity to beta-blockers compared with no-analog molecules, with an adsorption process occurring in monolayers, according to isotherm studies. Kinetic experiments indicated chemisorption as the predominant M-MIP/analyte interaction. The analytical curves were linear (R² > 0.98), and the limit of quantification was 3 µg L^-1 for all the analytes. Limits of detection ranged from 0.64 to 2.41 µg L^-1. Precisions (relative standard deviation) and accuracies (relative error) ranged from 3.95 to 21.20% and -17.05 to 18.93%, respectively. MPS-MS proved to be a simple, sensitive, and advantageous technique compared with conventional approaches. The analyses were fast, requiring no chromatographic separation and without ionic suppression. The method is aligned with green chemistry principles, requiring minimal sample, solvent, and sorbent amounts. MPS-MS successfully integrates sample preparation and ambient ionization mass spectrometry and holds great potential for application with other sorbents, samples, and analytes.

03 Apr 2023·Neurological Research

Beta-blocker carteolol and oxprenolol produce cutaneous analgesia in response to needle pinpricks in the rat

Article

Author: Chou, An-Kuo ; Chen, Yu-Wen

BACKGROUNDThis present study was undertaken to determine whether beta-blockers produce the cutaneous analgesic effect, comparing them with the long-acting local anesthetic bupivacaine.METHODSUsing a rat model of infiltrative cutaneous analgesia, the effect of 5 beta-blockers (oxprenolol, carteolol, butaxamine, metoprolol, and acebutolol) and bupivacaine was compared and eventually combined with epinephrine.RESULTSAmong 5 beta-blockers, oxprenolol exhibited the most potent and the longest duration of cutaneous analgesia. In dose-response studies, the rank order of efficacy (ED₅₀ [50% effective dose]) was bupivacaine (0.40 [0.35-0.47] μmol) > oxprenolol (2.33 [2.06-2.64] μmol) > carteolol (4.86 [4.27-5.53] μmol) (p< 0.01). Carteolol provoked a longer duration of analgesia (p< 0.01) than oxprenolol or bupivacaine on an equipotent basis (ED₂₅, ED₅₀, and ED₇₅). Adding epinephrine 1:200,000 to drug preparations (carteolol, oxprenolol, and bupivacaine) at ED₉₅ had a peripheral action in prolonging the duration of action.CONCLUSIONSOxprenolol and carteolol had greater potencies and longer durations of cutaneous analgesia than butaxamine, metoprolol, and acebutolol. Oxprenolol produced a similar duration of action when compared to bupivacaine, while carteolol had a greater duration of action than bupivacaine. Cutaneous analgesia of oxprenolol (or carteolol) plus adrenaline was greater than that of bupivacaine plus adrenaline.

01 Feb 2023·Journal of Cachexia, Sarcopenia and Muscle

The atypical β‐blocker S‐oxprenolol reduces cachexia and improves survival in a rat cancer cachexia model

Article

Author: Anker, Markus S. ; Millman, Oliver ; Álvarez Ladrón, Natalia ; Jové, Queralt ; von Haehling, Stephan ; Szymczyk, Agata ; Oosterlee, Annemijn ; Yuan, Luping ; Coats, Andrew J.S. ; Springer, Jochen ; Argiles, Josep M. ; Alves de Lima Junior, Edson ; López‐Soriano, Francisco Javier ; Anker, Stefan D. ; Palus, Sandra ; Busquets, Silvia

AbstractBackgroundBeta‐blockers and selected stereoisomers of beta‐blockers, like bisoprolol and S‐pindolol (ACM‐001), have been shown to be effective in preclinical cancer cachexia models. Here, we tested the efficacy of stereoisomers of oxprenolol in two preclinical models of cancer cachexia—the Yoshida AH‐130 rat model and the Lewis lung carcinoma (LLC) mouse model.Methods and ResultsIn the Yoshida AH130 hepatoma rat cancer cachexia model and compared with placebo, 50 mg/kg/d S‐oxprenolol (HR: 0.49, 95% CI: 0.28–0.85, P = 0.012) was superior to 50 mg/kg/d R‐oxprenolol (HR: 0.83, 95% CI 0.38–1.45, P = 0.51) in reducing mortality (= reaching ethical endpoints). Combination of the three doses (12.5, 25 and 50 mg/kg/d) that had a significant effect on body weight loss in the S‐oxprenolol groups vs the same combination of the R‐oxprenolol groups lead to a significantly improved survival of S‐oxprenolol vs R‐oxprenolol (HR: 1.61, 95% CI: 1.08–2.39, P = 0.0185). Interestingly, there is a clear dose dependency in S‐oxprenolol‐treated (5, 12.5, 25 and 50 mg/kg/d) groups, which was not observed in groups treated with R‐oxprenolol. A dose‐dependent attenuation of weight and lean mass loss by S‐oxprenolol was seen in the Yoshida rat model, whereas R‐oxprenolol had only had a significant effect on fat mass. S‐oxprenolol also non‐significantly reduced weight loss in the LLC model and also improved muscle function (grip strength 428 ± 25 and 539 ± 37 g/100 g body weight for placebo and S‐oxprenolol, respectively). However, there was only a minor effect on quality of life indicators food intake and spontaneous activity in the Yoshida model (25 mg/kg/S‐oxprenolol: 11.9 ± 2.5 g vs placebo: 4.9 ± 0.8 g, P = 0.013 and also vs 25 mg/kg/d R‐oxprenolol: 7.5 ± 2.6 g, P = 0.025). Both enantiomers had no effects on cardiac dimensions and function at the doses used in this study. Western blotting of proteins involved in the anabolic/catabolic homoeostasis suggest that anabolic signalling is persevered (IGF‐1 receptor, Akt) and catabolic signalling is inhibited (FXBO‐10, TRAF‐6) by S‐pindolol, but not he R‐enantiomer. Expression of glucose transporters Glut1 and Glut 4 was similar in all groups, as was AMPK.ConclusionsS‐oxprenolol is superior to R‐oxprenolol in cancer cachexia animal models and shows promise for a human application in cancer cachexia.

News (Medical) associated with Oxprenolol

14 Nov 2024

·www.globenewswire.com

Actimed Therapeutics Announces Professor David Ebsworth to Become Executive Chairman

Professor David Ebsworth to work closely alongside CEO Robin BhattacherjeeWill focus on fund raising efforts to support the planned IMPACT Phase 2b/3 trial for S-pindolol benzoate in cancer cachexiaProfessor Stefan Anker, Co-Founder of Actimed and Chair of the Scientific Advisory Board, also joins the Board of Directors London, UK – 14th November 2024. Actimed Therapeutics Ltd (“Actimed”), a UK based clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cancer cachexia and other muscle wasting disorders, announces that Professor David Ebsworth will assume the role of Executive Chairman of Actimed. At the same time, Professor Stefan Anker, Founder and Chair of the Actimed Scientific Advisory Board, will join the Board of the Company as a Non-Executive Director. David has been Non-Executive Chairman of Actimed Therapeutics since April 2018. He has over 40 years of experience in the healthcare industry and is a past CEO of Galenica AG, Vifor Pharma AG and past global head of the Pharmaceutical Division of Bayer AG. David has chaired numerous private and public pharmaceutical companies and served on many Boards as either Chairman of the audit, remuneration or nominations and governance committees. David is Chair of the Supervisory Board at Synlab AG and Board member at Sartorius AG. David also currently serves as Chairman of Nasdaq listed Verona Pharma PLC, which he moved from AIM to Nasdaq in 2020. Verona recently gained approval for and has successfully launched Ohtuvayre (ensifentrine). David will work closely in partnership with CEO Robin Bhattacherjee to support the Company’s fund-raising activities to finance the planned Phase 2b/3 IMPACT clinical trial programme for Actimed’s lead asset, S-pindolol benzoate, in cancer cachexia. Actimed received FDA approval of its Investigational New Drug (IND) application for the IMPACT programme in August 2023. The Company plans to dose patients in 2025. Professor Stefan Anker, MD, PhD, co-founded Actimed Therapeutics in 2017, having previously founded Myotec (later renamed PsiOxus Therapeutics). Stefan has 30 years of academic research experience in cachexia and clinical trials development. He is founding Editor-in-Chief of the Journal of Cachexia, Sarcopenia and Muscle as well as the founding president of the International Society on Sarcopenia, Cachexia and Wasting Disorders. Stefan has been and is a member of more than 50 international clinical trial steering committees and is a named author on over 1,300 research papers. As Actimed advances the clinical development of S-pindolol benzoate, Stefan’s expertise and knowledge will provide important support to the Board and the Company. Robin Bhattacherjee, Chief Executive Officer of Actimed Therapeutics commented “I greatly look forward to David taking on the role of Executive Chairman and dedicating more time to advancing our efforts to bring S-pindolol benzoate to patients. David’s industry track record, contact network and Board expertise speak for themselves and will further strengthen our ability to finance and complete our planned clinical programme for this highly promising asset.” David Ebsworth, Executive Chair of Actimed added “I look forward to working more closely with Robin to achieve our objectives. I am deeply committed to ensuring success for Actimed in our mission to transform care for the many patients suffering from cancer cachexia and other muscle wasting disorders. Cancer cachexia remains a poorly treated condition with few recent advances in therapy. At Actimed, I believe we have an exciting opportunity to advance the standard of care when we successfully finance and complete the clinical development of S-pindolol benzoate and I am pleased to provide my full support to Robin and the Leadership Team in pursuit of this.” *** About Actimed Therapeutics Actimed Therapeutics is a clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cachexia and other muscle wasting disorders, to transform the care of an underserved and vulnerable patient population. Cachexia is a wasting disease that is associated with cancer and other serious chronic illnesses and with significant morbidity and mortality. A significant number of cancer patients suffer from cachexia, and it is estimated that cachexia is responsible for up to 20% of all cancer deaths. Despite its prevalence and devastating clinical effects, there is no globally approved drug for the treatment or prevention of cancer-related cachexia. Actimed’s lead product, S-pindolol benzoate (ACM-001.1), targets multiple pathways that drive cachexia and has generated promising proof of concept Phase 2a clinical data in cachexia patients. Actimed is currently preparing for further clinical studies in cancer cachexia having received an Investigational New Drug (IND) approval from FDA for this programme in August 2023. Actimed also owns the global rights to its second asset, S-oxprenolol, which is being developed by the Company for the muscle wasting seen in amyotrophic lateral sclerosis (ALS) where loss of body mass and muscle wasting may impact survival. Actimed has licensed the global rights to develop and commercialise S-oxprenolol for cancer cachexia and any other indications outside of ALS to US company Faraday Pharmaceuticals. FOR MORE INFORMATIONActimed Therapeuticswww.actimedtherapeutics.com MEDiSTRAVA Frazer Hall, Erica HollingsworthTel: +44 (0)203 928 6900Email: actimed@medistrava.com ___________________________

Phase 2Executive ChangeDrug Approval

04 Sep 2024

·www.globenewswire.com

Actimed Therapeutics Announces US FDA Grant of Orphan Drug Designation to S-oxprenolol (ACM-002) for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

London, UK – 4th September 2024. Actimed Therapeutics Ltd (“Actimed”), a UK based clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of cancer cachexia and other muscle wasting disorders, announces that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to S-oxprenolol (ACM-002) for the treatment of amyotrophic lateral sclerosis (ALS). ALS (also known as Lou Gehrig’s disease) is a progressive, fatal neuromuscular disease that affects nerve cells in the brain and spinal cord, eventually leading to a loss of muscle control and paralysis. ALS prevents motor neurons sending impulses from the brain and spinal cord to the muscles, causing muscle atrophy and weakness and has a mean survival of 3.5 years. Voluntary muscle action is progressively lost and in late-stage ALS patients may have difficulty communicating, swallowing, moving, and breathing. There is currently no cure for ALS. Cachexia, a complex wasting disease, may occur in the early stages of ALS and has a significant impact on quality of life, proving terminal in some patients. In pre-clinical ALS models, S-oxprenolol has demonstrated significant benefits including slowing disease progression, improvement in survival, attenuation of muscle loss, motor neuron protection, reduction in loss of body mass and improvements in lean body mass1. Robin Bhattacherjee, Chief Executive Officer of Actimed Therapeutics commented “We are pleased to receive Orphan Drug Designation for S-oxprenolol in ALS, where loss of body mass and muscle wasting can have a significant impact on survival. ALS is a devastating orphan disease of high, unmet medical need and the early non-clinical data we have generated for S-oxprenolol in this indication suggest that it could have a potential role in meeting some of the important needs of this under-served patient population”. FDA Orphan Drug Designation is granted to investigational therapies which are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the United States. Orphan Drug Designation provides several benefits to drug developers, including certain development cost benefits in the US, increased FDA interaction and eligibility for seven-year market exclusivity following approval. *** About Actimed Therapeutics Actimed Therapeutics is a clinical stage specialty pharmaceutical company focused on bringing innovation to the treatment of muscle wasting disorders to transform the care of an underserved and vulnerable patient population. The lead area of focus for Actimed is specifically in cachexia. Cachexia is a wasting disease that is associated with cancer and other serious chronic illnesses and with significant morbidity and mortality. A significant number of cancer patients suffer from cachexia2 and it is estimated that cachexia is responsible for up to 20% of all cancer deaths3. A recent meta-analysis demonstrated that cachexia was associated with an 82% higher relative risk of mortality in patients with NSCLC versus no cachexia4. Despite its prevalence and devastating clinical effects, there is no globally approved drug for the treatment or prevention of cancer-related cachexia. The lead product of Actimed, S-pindolol benzoate (ACM-001.1) targets multiple pathways that drive cachexia and has generated promising proof of concept Phase 2a clinical data in cachexia patients. Actimed is currently preparing for further clinical studies in cancer cachexia having received an Investigational New Drug (IND) approval from FDA for this programme in August 2023. Actimed also owns the global rights to its second asset, S-oxprenolol, which is being developed by the Company for the muscle wasting seen in amyotrophic lateral sclerosis (ALS) where loss of body mass and muscle wasting may impact survival5. Actimed has licensed the global rights to develop and commercialise S-oxprenolol for cancer cachexia and any other indications outside of ALS to US company Faraday Pharmaceuticals. FOR MORE INFORMATIONActimed Therapeuticswww.actimedtherapeutics.com MEDiSTRAVA ConsultingFrazer Hall, Erica HollingsworthTel: +44 (0)203 928 6900Email: actimed@medistrava.com ___________________________ 1Suzuki et al, JCSM 2018; 9, 183-212. (Poster 5-17, page 200)2 Anker M et al., J. Cachexia, Sarcopenia and Muscle; 2019: 10: 22 – 243 Argilés JM et al, Nat Rev Cancer 2014; 14:754-624 Bonomi P. et al. The mortality burden of cachexia in patients with non-small-cell lung cancer: A meta-analysis; International Conference of Sarcopenia, Cachexia and Wasting Disorders, June 17 – 18 2023, Stockholm, abstract 2-18, page 1395Wolf J et al., PMID 28184974 DOI: 10.1007/s00115-117-0293

Phase 2Orphan Drug

04 Sep 2024

·www.pharmaceutical-technology.com

Actimed’s ALS candidate wins FDA orphan drug designation

ALS prevents motor neurons from sending impulses from the brain and spinal cord to the muscles, causing muscle atrophy and weakness. Image credit: Shutterstock / CC7. The US Food and Drug Administration (FDA) has granted an orphan drug designation to Actimed Therapeutics’ S-oxprenolol (ACM-002) for the treatment of amyotrophic lateral sclerosis (ALS). The UK-based pharma company will now be in line for tax credits for US-based clinical trials, and if the therapy is approved, the potential for seven years of market exclusivity in the designated indication, as per a 4 September press release. Actimed says S-oxprenolol shares “a similar pharmacology” to S-pindolol, which is an anabolic/catabolic transforming agent. S-pindolol benzoate, Actimed’s lead product, is being investigated for the treatment of the metabolic weight loss syndrome called cachexia. With S-oxprenolol, Actimed is targeting S-pindolol’s mechanistic approach in the wasting syndrome to address the loss of body mass and muscle wasting seen in ALS. ALS is the most common form of motor neuron disease. Muscle wasting is seen in patients as motor neuron degeneration means muscles no longer receive electrical signals. See Also: ESC 2024: Beta blocker treatment paradigm shifts for myocardial infarction Novavax wins FDA emergency approval for updated Covid-19 vaccine There are currently six FDA-approved therapies for ALS, though the agency has developed a five-year plan to accelerate the development of more treatments and improve medicine access. There have been a few recent setbacks in the space, including Amylyx Pharmaceutical’s Phase III failure and Ionis/Biogen’s decision to discontinue the development of their ALS candidate. In preclinical ALS models, S-oxprenolol has demonstrated an ability to attenuate muscle loss, improve lean body mass, and reduce the loss of overall body mass, amongst other benefits. Oxprenolol is a beta blocker usually used for the treatment of heart conditions such as angina and high blood pressure. While Actimed has not disclosed the mechanism of action in ALS, the related compound S-pindolol increases anabolism and muscle by partial beta-2 receptor agonism. Actimed is currently conducting trials for S-pindolol in cancer cachexia, a sub-type of the syndrome found in cancer patients. The compound has demonstrated positive proof of concept data in a Phase IIa study, with further clinical trials planned according to the company. Actimed has yet not unveiled details of a clinical programme for S-oxprenolol. Nonetheless, the company has already licensed the drug’s global rights for cancer cachexia and non-ALS indications to US company Faraday Pharmaceuticals. The deal, signed in 2021, included an upfront payment of $550,000 and $126.2m in milestone payments. Actimed’s CEO Robin Bhattacherjee said: “The early non-clinical data we have generated for S-oxprenolol in this indication suggest that it could have a potential role in meeting some of the important needs of this under-served patient population.”

Drug ApprovalPhase 2Orphan DrugClinical ResultPhase 3

100 Deals associated with Oxprenolol

External Link

KEGG	Wiki	ATC	Drug Bank
D08318	Oxprenolol	C07AA02	DB01580

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Angina Pectoris	CN	Beijing Wanhui Double-Crane Pharmaceutical Co. Ltd.	-
Arrhythmias, Cardiac	CN	Beijing Wanhui Double-Crane Pharmaceutical Co. Ltd.	-
Hypertension	CN	Beijing Wanhui Double-Crane Pharmaceutical Co. Ltd.	-

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cachexia	Preclinical	GB	Actimed Laboratories, Inc.	24 Nov 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis