Adehl (colforsin dapropate) / Nippon Kayaku - LARVOL DELTA

Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas. (PubMed, Sci Signal) - "In vivo, colforsin daropate reduced tumor growth, synergized with cisplatin (a standard chemotherapy in ovarian cancer care), and improved host survival in subcutaneous and intraperitoneal xenograft models. These antitumor effects of colforsin daropate were mediated in part by its reduction in the abundance and transcriptional activity of the oncoprotein c-MYC, which is often increased in HGSOC. Our findings demonstrate that colforsin daropate may be a promising therapeutic that could be combined with conventional therapies to treat HGSOC."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • MYC

A conserved transcription factor regulatory program promotes tendon fate. (PubMed, Dev Cell) - "Notably, Creb1a/CREB1 and Ebf1a/Ebf3a/EBF1 overexpression facilitated tenogenic induction in zebrafish and human pluripotent stem cells. Together, our work identifies the functional conservation of two transcription factors in promoting tendon fate."

Journal • CREB1 • EBF1

The role of hypoxia inducible factor modulation and defatting in discarded steatotic human livers preserved with normothermic machine perfusion (NMP): observations from an ex-situ whole blood transplant model (TTS 2024) - "We have previously reported dosing schedules for pharmacological HIF modulators including deferoxamine (DFO, a potent activator of both HIF-1a & HIF-2a) with selective HIF-2a inhibition using PT2385 (a HIF-2a dimerisation inhibitor) during NMP. The aim of the present study was to compare the effect of an established NMP defatting protocol (DeFat, comprising of insulin/glucose reduction, L-carnitine, NKH477 and lipid filter) with and without the adjunct of HIF modulators (DeFat-HIF, addition of DFO & PT2385) during ex-situ perfusion. Six sequential discarded livers (DeFat, n=3 and DeFat-HIF, n =3) were perfused with pRBC using the OrganOx metra over 12h, flushed and reperfused for 6h with whole blood (ex-situ transplant model), (Table1)... The DeFat-HIF protocol demonstrated a decrease in the presence of Ld-MaS and comparable perfusion biochemistry to the established DeFat protocol. The effect of these interventions on ischaemia-reperfusion injury remain to be..."

Reperfusion Injury • Transplantation • EPAS1 • HIF1A

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study. (PubMed, Trials) - "This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths."

Journal • Cardiovascular • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Reperfusion Injury • Transplantation

Identification of somatic mutation-driven enhancers and their clinical utility in breast cancer. (PubMed, iScience) - "We identified eight candidate drugs such as erastin, colforsin, and STOCK1N-35874 targeting the mutated enhancer. Our findings suggest that somatic mutations contribute to breast cancer subtype progression by altering enhancer activity, which could be potential candidates for cancer therapy."

Journal • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • ALOX15B • BRCA • HER-2

"Creole Dinner with Alizadehlab lymphomaniacs!" (@AshAlizadeh)

Hematological Malignancies • Lymphoma • Oncology

Glia maturation factor-β induces ferroptosis by impairing chaperone-mediated autophagic degradation of ACSL4 in early diabetic retinopathy. (PubMed, Redox Biol) - "GMFB antibody, lysosome activator NKH477, CMA activator QX77, and ferroptosis inhibitor Liproxstatin-1 were all effective in preventing early diabetic retinopathy and maintaining normal visual function, which has powerful clinical application value. Our research broadens the understanding of the relationship between autophagy and ferroptosis and provides a new therapeutic target for the treatment of DR."

Journal • CNS Disorders • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders • ACSL4

"our approach is data sharing, #OpenScience collaboration @ZadehLab @UHN @pmcancercentre @UHN_Research @KBI_UHN @DrDonWeaver @UHN_Surgery @bradwouters @akeithstewart #nf #endNF #neurofibromatosis @nfopensci @nfnetwork @ChildrensTumor @Sagebio @allawayr" (@gelarehzadeh)

Fibrosis • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor

[VIRTUAL] Beta1-Adrenergic cAMP Signaling is Uncoupled after Acute Treatment of Anthrax Lethal Toxin in Cardiomyocytes in Normal Rats (AHA 2021) - "We examined acute exposure of LeTx caused alterations of myocyte β1- and β3-AR expression and myocyte basal contraction and relaxation and responses to isoproterenol (ISO), a β-AR agonist, and colforsin (COLF), a cAMP activator...Acute treatment of LeTx causes cardiac myocyte β1-AR uncoupling from cAMP-mediated signaling and impairs myocyte β-adrenergic reserve. These results suggest that the early changes in cardiac subtypes of β-AR signal transduction system may mediate the connection between the acute and chronic cardiac action of LeTx."

Preclinical • CNS Disorders • Depression • Psychiatry

Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM). (PubMed, Biomedicines) - "The efficacy of TMRM-PDT in certain GBM cell lines may be potentiated by adenylate cyclase activator NKH477. Together, these findings identify TMRM as a prototypical mitochondrially targeted photosensitizer with beneficial features which may be suitable for preclinical and clinical translation."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Identifying SARS-CoV-2 Entry Inhibitors through Drug Repurposing Screens of SARS-S and MERS-S Pseudotyped Particles. (PubMed, ACS Pharmacol Transl Sci) - "We discovered six compounds (cepharanthine, abemaciclib, osimertinib, trimipramine, colforsin, and ingenol) to be broad spectrum inhibitors for spike-mediated entry. This work could contribute to the development of effective treatments against the initial stage of viral infection and provide mechanistic information that might aid the design of new drug combinations for clinical trials for COVID-19 patients."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

"https://t.co/9HDSEADEHl" (@KalksteinNir)

Cyclic AMP-Dependent Post-Translational Modification of Neuronal Nitric Oxide Synthase Neuroprotects Penile Erection in Rats. (PubMed, BJU Int) - "Collectively, BCNI impairs nNOS function in the penis and MPG by mechanisms involving its phosphorylation and uncoupling in association with increased oxidative stress, resulting in erectile dysfunction. PKA activation by colforsin reverses these molecular changes and preserves penile erection in the face of BCNI."

Journal • Biosimilar

Role of adenosine in functional recovery following anoxic coma in Locusta migratoria. (PubMed, J Insect Physiol) - "A cAMP inhibitor, NKH 477, delayed recovery time in male animals. Our results show that the rate of recovery in insect systems is affected by the presence of adenosine."

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Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: A dose-response study. (PubMed, PLoS One) - "Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis."

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