cercosporamide / Eli Lilly - LARVOL DELTA

Cercosporamide, a polyketide-derived fungal metabolite, serves as an antifungal agent against phytopathogenic fungi. (PubMed, Mycoscience) - "Cercosporamide exhibited strong antifungal activities against two pepper anthracnose pathogens, Colletotrichum gloeosporioides and C. scovillei with EC50 values of 3.8 and 7.0 µg/mL, respectively. This study suggests the potential application of cercosporamide as an effective antifungal agent in controlling anthracnose in pepper."

Journal • Oncology

Antifungal activity of cercosporamide produced by Phaeosphaeriaceae GV-1 against pathogenic fungi. (PubMed, Braz J Microbiol) - "Cercosporamide showed antifungal activity in vitro against 13 of 16 strains of medical importance tested, with the most susceptible species being Candida tropicalis, with MIC and MFC of 15.6 μg/mL. Thus, cercosporamide might be considered a promising therapeutic antifungal agent."

Journal • Infectious Disease • Oncology • Transplantation

Inhibition of MNK pathway sensitizes nasopharyngeal carcinoma to radiotherapy. (PubMed, Anticancer Drugs) - "Furthermore, we tested three pharmacological MNK inhibitors (eFT508, CGP57380, and cercosporamide) and found that they were effective against radioresistant NPC cells and synergized with irradiation. Our research highlights the activation of MNK-mediated survival mechanisms in NPC in response to radiotherapy and the potential of combining radiation with MNK inhibitors as a sensitizing strategy. Notably, eFT508 is currently being investigated in clinical trials for cancer treatment, and our findings may prompt the initiation of clinical trials using eFT508 in radioresistant NPC patients."

Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • EIF4E

Phoma spp. an untapped treasure of cytotoxic compounds: current status and perspectives. (PubMed, Appl Microbiol Biotechnol) - "The metabolite spectrum includes bioactive compounds like phomenon, phomin, phomodione, cytochalasins, cercosporamide, phomazines, and phomapyrone reported from various Phoma spp...also secrete cytotoxic and antitumor compounds. • The secondary metabolites can be used for the development of anticancer agents."

Journal • Review • Oncology

MNK/eIF4E inhibition overcomes anlotinib resistance in non-small cell lung cancer. (PubMed, Fundam Clin Pharmacol) - "Importantly, observations from in-vitro experiments are consistent in in vivo anlotinib-resistant and anlotinib-sensitive NSCLC cancer xenograft mouse models. Our work is the first to reveal that eIF4E is involved intimately in anlotinib resistance development in NSCLC, and this eIF4E activation can be reversed by cercosporamide or other MNK inhibitors."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EIF4E

Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets. (PubMed, Front Pain Res (Lausanne)) - "Despite this, peripheral voltage-gated cation channels retain their promise as therapeutic targets. The way forward may include (i) further structural refinement of K channel activators such as retigabine and ASP0819 to improve selectivity and limit toxicity; use or modification of Na channel blockers such as vixotrigine, PF-05089771, A803467, PF-01247324, VX-150 or arachnid toxins such as Tap1a; the use of Ca channel blockers such as TTA-P2, TTA-A2, Z 944, ACT709478, and CNCB-2; (ii) improving methods for assessing "pain" as opposed to nociception in rodent models; (iii) recognizing sex differences in pain etiology; (iv) tailoring of therapeutic approaches to meet the symptoms and etiology of pain in individual patients via quantitative sensory testing and other personalized medicine approaches; (v) targeting genetic and biochemical mechanisms controlling channel expression using anti-NGF antibodies such as tanezumab or re-purposed drugs such as vorinostat, a..."

Journal • Review • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lymphoma • Neuralgia • Oncology • Pain • Rheumatoid Arthritis • Rheumatology • T Cell Non-Hodgkin Lymphoma • TAP1

Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases. (PubMed, Molecules) - "Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure-activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CDK1 • PIM1

Targeting of MNK/eIF4E overcomes chemoresistance in cervical cancer. (PubMed, J Pharm Pharmacol) - "This work demonstrates the ability of cercosporamide to overcome chemoresistance and highlight preferential inhibition of eIF4E via MNK inhibition in cervical cancer."

Journal • Cervical Cancer • Oncology • Solid Tumor • EIF4E

Cercosporamide inhibits bone morphogenetic protein receptor type I kinase activity in zebrafish. (PubMed, Dis Model Mech) - "Importantly, cercosporamide rescued the developmental defects caused by constitutively active Alk2 in zebrafish embryos. Taken together, we believe cercosporamide may be the first of a new class of molecules with potential to be developed further for clinical use against diseases that are causally linked to overactivation of BMPR signaling, including Fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma."

Journal • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Preclinical evidence that MNK/eIF4E inhibition by cercosporamide enhances the response to antiangiogenic TKI and mTOR inhibitor in renal cell carcinoma. (PubMed, Biochem Biophys Res Commun) - "Combination indices value indicated that the combination of cercosporamide with sunitinib or temsirolimus are synergistic in RCC. Mechanistically, we found that cercosporamide suppressed pro-angiogenic factors VEGF and HIFα, inhibited EMT and reduced pro-survival and cell cycle proteins; and furthermore this was attributed to cercosporamide's ability in inhibiting eIF4E. This work demonstrates the anti-RCC activity of cercosporamide through targeting both RCC tumor cells and angiogenesis, and provides the first preclinical proof-of-concept of evidence of Mnk inhibition for RCC treatment."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EIF4E

IL-6 induced upregulation of T-type Ca currents and sensitization of DRG nociceptors is attenuated by MNK inhibition. (PubMed, J Neurophysiol) - "IL-6 induced DRG nociceptor excitability is attenuated in mice lacking eIF4E phosphorylation, in MNK1/2 mice and by the nonselective MNK1/2 inhibitor cercosporamide. Our findings are consistent with a model wherein MNK-eIF4E signaling controls the translation of signaling factors that regulate T-type VGCCs in response to IL-6 treatment. Inhibition of MNK with eFT508 disrupts these events, thereby preventing nociceptor hyperexcitability."

Journal • Pain • EIF4E • IL6

In search for potential antidiabetic compounds from natural sources: docking, synthesis and biological screening of small molecules from Lycium spp. (Goji). (PubMed, Heliyon) - "Current clinical antidiabetic drugs, like rosiglitazone 1, have been implicated in some serious side effects like edema, weight gain, and heart failure, making it necessary to find alternative agents...In vivo results suggest that the proposed antidiabetic property of Lycium species may not be due to tyramine derivatives alone. Further studies of tyramine derivatives or enriched extract(s) for other bioactivities like hypocholesterolemic activities, and studies of novel isolated compounds from Goji will enable a more complete understanding of their bioactivities."

Journal

Identification of inhibitors based on molecular docking: Thyroid hormone transporter MCT8 as a target. (PubMed, Curr Drug Discov Technol) - "This study reveals that these compounds could be promising candidates for further evaluation for AHDS prevention."

Journal

Adult Mouse Sensory Neurons on Microelectrode Arrays Exhibit Increased Spontaneous and Stimulus-Evoked Activity in the Presence of Interleukin-6. (PubMed, J Neurophysiol) - "Acute responsiveness to IL6 is inhibited by treatment with a MNK1/2 inhibitor cercosporamide. In total, these findings suggest that adult mouse DRG neurons on multiwell MEAs are applicable to ongoing efforts to discover peripheral analgesic and their mechanisms of action."

Journal

A metabolite of endophytic fungus Cadophora orchidicola from Kalimeris indica serves as a potential fungicide and TLR4 agonist. (PubMed, J Appl Microbiol) - "This study indicates endophytic fungi are good resources for natural bioactive metabolites. It also suggests that cercosporamide is a potential fungicide and TLR4 agonist."

Journal