Bronica (seratrodast) / Takeda - LARVOL DELTA

Visible-light-mediated decarboxylative allylation of vinylcyclopropanes with α-keto acids toward β,γ-alkenyl ketones. (PubMed, Org Biomol Chem) - "Mechanistic studies support a radical-polar crossover pathway involving photogenerated acyl radicals and ring-opening of VCPs. The synthetic utility of this method is demonstrated by the concise, five-step synthesis of the clinical drug Seratrodast."

Journal

Role of Milk Intake in Modulating Serum Lipid Profiles and Gut Metabolites. (PubMed, Metabolites) - "The results further confirmed that milk intake has a beneficial effect on blood lipid health by altering multiple metabolites in the serum and the gut. This study provides novel evidence that milk consumption is beneficial to health and is a reference for guiding people to a healthy diet."

Journal • Metabolic Disorders

Seratrodast inhibits ferroptosis by suppressing lipid peroxidation. (PubMed, Cell Death Dis) - "While seratrodast itself does not inhibit lipid peroxidation, it exhibits potent radical-trapping antioxidant activity upon reduction to its corresponding hydroquinone form-analogously to ubiquinone and vitamin K. Importantly, seratrodast ameliorated the severity of renal ischemia-reperfusion injury in mice. Together, this study provides a drug repurposing case, where seratrodast-a marketed drug-can undergo fast-forward preclinical/clinical development for the inhibition of ferroptosis in distinct degenerative diseases."

Journal • Asthma • Cardiovascular • CNS Disorders • Immunology • Pulmonary Disease • Reperfusion Injury • Respiratory Diseases

Doxorubicin alters G-protein coupled receptor-mediated vasocontraction in rat coronary arteries. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The vasocontractile responses by activation of endothelin receptor type A (ETA) and type B (ETB), serotonin receptor 1B (5-HT1B) and thromboxane A2 prostanoid receptor (TP) were investigated by a sensitive myography using specific agonists, while the specificity of the GPCR agonists was verified by applying selective antagonists (i.e. ETA and ETB agonist = 10- 14-10- 7.5 M endothelin-1 (ET-1); ETA antagonist = 10 µM BQ123; ETB agonists = 10- 14-10- 7.5 M sarafotoxin 6c (S6c) and ET-1; ETB antagonist = 0.1 µM BQ788; 5-HT1B agonist = 10- 12-10- 5.5 M 5-carboxamidotryptamine (5-CT); 5-HT1B antagonist = 1 µM GR55562; TP agonist = 10- 12-10- 6.5 M U46619; TP antagonist = 1 µM Seratrodast). Our results show that 0.5 µM Doxo incubation of LAD segments leads to an increased VSMC vasocontraction through the ETB, 5-HT1B and TP GPCRs, with a 2.2-fold increase in ETB-mediated vasocontraction at 10- 10.5 M S6c, a 2.0-fold increase in 5-HT1B-mediated..."

Journal • Preclinical • Cardiovascular • Oncology • EDN1 • EDNRA

Synthesis of 1,3-Dienes via Ligand-Enabled Sequential Dehydrogenation of Aliphatic Acids. (PubMed, J Am Chem Soc) - "Free aliphatic acids of varying complexities, including the antiasthmatic drug seratrodast, were found to be compatible with the reported protocol. Considering the high lability of 1,3-dienes and lack of protecting strategies, dehydrogenation of aliphatic acids to reveal 1,3-dienes at the late stage of synthesis offers an appealing strategy for the synthesis of complex molecules containing such motifs."

Journal • Asthma • Immunology

Ligand-Enabled Pd(II)-Catalyzed β-Methylene C(sp)-H Arylation of Free Aliphatic Acids. (PubMed, J Am Chem Soc) - "This new transformation provides a disconnection for alkylation of arenes with simple aliphatic acids. A variety of free aliphatic acids, including the antiasthmatic drug seratrodast, were compatible with the reported protocol."

Journal • Asthma • Immunology

Seratrodast, a thromboxane A2 receptor antagonist, inhibits neuronal ferroptosis by promoting GPX4 expression and suppressing JNK phosphorylation. (PubMed, Brain Res) - "Drug repurposing is a promising strategy for the rapid generation of new candidate drugs from the market drugs with new therapeutic indications, such as the best-selling drug thalidomide. Seratrodast increased the latency of seizures and reduced seizure duration in pentylenetetrazole-induced seizures. Our results suggest Seratrodast might be either a ferroptosis inhibitor or a novel lead compound for further optimization of novel drug discovery."

Journal • CNS Disorders • Epilepsy • GPX4

Eicosanoid receptors as therapeutic targets for asthma. (PubMed, Clin Sci (Lond)) - "Drugs targeting proinflammatory eicosanoid receptors, including CysLT1, the receptor for LTD4 (montelukast) and TP, the receptor for TXA2 (seratrodast) are currently in use, whereas antagonists of a number of other receptors, including DP2 (PGD2), BLT1 (LTB4), and OXE (5-oxo-ETE) are under investigation. This review summarizes the contributions of eicosanoid receptors to the pathophysiology of asthma and the potential therapeutic benefits of drugs that target these receptors. Because of the multifactorial nature of asthma and the diverse pathways affected by eicosanoid receptors, it will be important to identify subgroups of asthmatics that are likely to respond to any given therapy."

Journal • Asthma • Immunology • Multiple Sclerosis • Pulmonary Disease • Respiratory Diseases

Centruroides margaritatus scorpion complete venom exerts cardiovascular effects through alpha-1 adrenergic receptors. (PubMed, Comp Biochem Physiol C Toxicol Pharmacol) - "The direct vascular and probably the cardiac alpha-1 effects likely explain the transient hypertension and the maintenance of cardiac function, while interval lengthening may be due to K channel blockage. Afterwards, the effects of both the alpha-1 pathway and the K channel pathway converged, resulting in fatal cardiovascular shock. This knowledge could aid in understanding the dynamics of the effects of the venom and in designing treatments to address its cardiovascular effects."

Journal • Cardiovascular • Hypertension • ADRA1B

"thanks dear, any idea, can roflumilast/seratrodast can be of some help in covid hypoxia." (@drakchaurasia)

Effects of Displacement-Distortion of Potential Energy Surfaces on Nonadiabatic Electron Transfers via Conical Intersections: Application to SO2 and Trans-1,3,5-Hexatriene. (PubMed) - J Phys Chem A - "The validity of our formalism is verified through comparison with previous work in a certain limit of our results for case of displaced harmonic oscillator. Finally for illustration, the derived expressions have been applied to determine the electronic population dynamics at conical intersections for SO2 and trans-1,3,5-hexatriene molecules."

Journal • Biosimilar

Endothelium-dependent and endothelium-independent effects of 1-nitro-2-propylbenzene on rat aorta. (PubMed, Fundam Clin Pharmacol) - "Such potentiation was unaltered by the thromboxane-prostanoid receptor antagonist seratrodast, but was abolished by endothelium removal or by preincubation of endothelium-intact preparations with L-NAME, ODQ or by ruthenium red and HC-030031, blockers of subtype 1 of ankyrin transient receptor potential (TRPA ) channels...NPB has also endothelium-dependent potentiating properties on phenylephrine-induced contractions, a phenomenon that putatively required a role of endothelial TRPA channels. The present findings reinforce the notion that the functional group NO in the aliphatic chain of these nitro compounds determines favorably their vasodilator properties."

Journal • Preclinical

Regulation of liver regeneration by prostaglandin E and thromboxane A following partial hepatectomy in rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Contrariwise, seratrodast hindered the normal regeneration process and completely abolished the proliferative effect of celecoxib. In conclusion, TXA has a major role in liver regeneration that could greatly mediate the triggering effect of celecoxib on hepatocytes proliferation following PHx."

Journal • Preclinical • CCND1 • CTNNB1 • IL6

Neryl butyrate induces contractile effects on isolated preparations of rat aorta. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Antagonists of α-adrenergic receptors (prazosin and yohimbine), but not the thromboxane-prostanoid receptor seratrodast, reversed the contraction induced by neryl butyrate. In conclusion, the contractile effects of neryl butyrate were inhibited by α-adrenergic antagonists, indicating the involvement of α-adrenoceptors in the mechanism of action. In vivo, neryl butyrate caused hypotension, suggesting that other systemic influence than vasoconstriction may occur."

Journal • Preclinical

Catalytic Redox Chain Ring Opening of Lactones with Quinones To Synthesize Quinone-Containing Carboxylic Acids. (PubMed, Org Lett) - "A novel route to the anti-asthma drug Seratrodast was developed. Mechanism study suggests that the redox chain reaction likely undergoes a carbocation intermediate."

Journal