Protara (acadesine) / Teva - LARVOL DELTA

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation. (PubMed, Int J Mol Sci) - "Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs...The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters...Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review. (PubMed, Cells) - "However, there is an increasing number of studies showing that numerous AICAr effects, previously attributed to AMPK activation, are in fact AMPK-independent. This review aims to give an overview of the present knowledge on AMPK-dependent and AMPK-independent effects of AICAr on metabolism, hypoxia, exercise, nucleotide synthesis, and cancer, calling for caution in the interpretation of AICAr-based studies in the context of understanding AMPK signaling pathway."

Journal • Review • Hematological Malignancies • Leukemia • Oncology

"#ProtaraTherapeutics to Participate in the #OppenheimerAnnualHealthcareConference $TARA https://t.co/8DVIXhsA4x" (@1stOncology)

Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells. (PubMed, PLoS One) - "Our results suggest that acadesine suppresses TNF-α induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases."

Journal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • TNFA

Compound C Protects Against Cisplatin-Induced Nephrotoxicity Through Pleiotropic Effects. (PubMed, Front Physiol) - "AICAR (Acadesine/AICA riboside) as an activator of AMPK, can protect renal tubular cells from cisplatin induced apoptosis. Instead, compound C protected cisplatin nephrotoxicity by inhibiting P53 and endoplasmic reticulum (ER) stress. Therefore, compound C may protect against cisplatin-induced nephrotoxicity through pleiotropic effects."

Journal • Acute Kidney Injury • Nephrology • Renal Disease

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells. (PubMed, Chem Biol Interact) - "Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis...However, this initiative effect of ROS can be reversed by N-Acetyl-l-cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells."

Journal • Bladder Cancer • Genito-urinary Cancer • Infectious Disease • Oncology • Solid Tumor • Urothelial Cancer

A prospective targeted serum metabolomics study of pancreatic cancer in postmenopausal women. (PubMed, Cancer Prev Res (Phila)) - "The area under the ROC curve was 0.83 in the discrimination analysis based on the levels of L-1MT, acadesine, and aspartic acid. None of the metabolites was validated in additional independent 18 case/control pairs. No significant association was found between the examined metabolites and undiagnosed pancreatic cancer."

Clinical • Journal • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Women's Health

Adenosine receptor targeting in health and disease (Expert Opin Investig Drugs) - Selective ligands of A1, A2A, A2B & A3 adenosine receptors are likely to find applications in the treatment of pain, ischemic conditions, glaucoma, asthma, arthritis, cancer & other disorders in which inflammation is a feature; The aim of this review is to provide an overview of the present knowledge regarding the role of these adenosine receptors in health & disease

Expert opinion • Cardiovascular

Acadesine Circumvents Azacitidine Resistance in Myelodysplastic Syndrome and Acute Myeloid Leukemia. (PubMed, Int J Mol Sci) - "Despite a very good response in one out 4 patients, we stopped this trial because the highest Aca dose (210 mg/kg) caused serious renal side effects in several patients. In conclusion, the side effects of high Aca doses preclude its use in patients with strong comorbidities."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

AICAR induces AMPK-independent programmed necrosis in prostate cancer cells. (PubMed) - Biochem Biophys Res Commun - "AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, which induces cytotoxic effect to several cancer cells...CYPD inhibitors (cyclosporin A and sanglifehrin A) as well as CYPD shRNAs dramatically attenuated AICAR-induced prostate cancer cell necrosis and cytotoxicity...ROS scavengers (N-acetylcysteine and MnTBAP), but not AMPKα shRNAs, largely inhibited prostate cancer cell necrosis and cytotoxicity by AICAR. In summary, the results of the present study demonstrate mechanistic evidences that AMPK-independent programmed necrosis contributes to AICAR's cytotoxicity in prostate cancer cells."

Journal • Biosimilar • Genito-urinary Cancer • Oncology • Prostate Cancer

AICAR activates ER stress-dependent apoptosis in gallbladder cancer cells. (PubMed) - Biochem Biophys Res Commun - "AICAR (5-Aminoimidazole-4-carboxamide riboside or acadesine) is an AMP-activated protein kinase (AMPK) agonist, its activity in human gallbladder cancer cells was evaluated here. Contrarily, salubrinal (the ER stress inhibitor), z-ATAD-fmk (the caspase-12 inhibitor) or CHOP shRNAs significantly attenuated AICAR-induced gallbladder cancer cell apoptosis. Together, we conclude that AICAR-induced gallbladder cancer cell apoptosis requires ER stress activation, but is independent of AMPK."

Journal • Biosimilar • Bladder Cancer • Gastrointestinal Cancer • Oncology • Urothelial Cancer

Synthesis of C-labeled 5-Aminoimidazole-4-carboxamide-1-β-D-[ C ] ribofuranosyl 5'-monophosphate. (PubMed, J Labelled Comp Radiopharm) - "Our method employs a hybrid enzymatic and chemical synthesis approach that applies an enzymatic conversion from adenosine to inosine followed by a ring-cleavage of the protected inosine. A direct phosphorylation of the resulting 2',3'-isopropylidine acadesine (5) was developed to yield the title compound in 99% purity following ion exchange chromatography."

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The role of AMPK/mTOR modulators in therapy of acute myeloid leukemia. (PubMed, Curr Med Chem) - "...Numerous studies demonstrate that drugs that inhibit mechanistic target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects in promoting differentiation and blocking proliferation of AML. Most of these drugs are already in use for other purposes; rapalogs as immunosuppressants, biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide ribonucleoside (AICAr, acadesine) as an exercise mimetic. Although most of these pharmacological modulators have been widely used for decades, their mechanism of action is only partially understood. In this review, we summarize the role of AMPK and mTOR in hematological malignancies and discuss the possible role of pharmacological modulators in proliferation and differentiation of leukemia cells."

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The Chinese medicine Chai Hu Li Zhong Tang protects against non-alcoholic fatty liver disease by activating AMPKα. (PubMed, Biosci Rep) - "The AMPK agonist, acadesine (AICAR), was used as a positive control compound. CHLZT protects against NAFLD by activating AMPKα, and also by inhibiting ACC activity, downregulating SREBP2 and HMGR, and upregulating PPAR-γ. Our results suggest that CHLZT might be useful for treating NAFLD in the clinic."

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