AMF-26 / Eisai - LARVOL DELTA

Brefeldin A and M-COPA block the export of RTKs from the endoplasmic reticulum via simultaneous inactivation of ARF1, ARF4, and ARF5. (PubMed, J Biol Chem) - "Inhibitors of protein export from the endoplasmic reticulum (ER), such as brefeldin A (BFA) and 2-methylcoprophilinamide (M-COPA), can suppress the activation of mutant RTKs in cancer cells, suggesting that RTK mutants cannot initiate signaling in the ER...Consistent with these results, in vitro pulldown assays showed that BFA/M-COPA blocked the function of ARF1, ARF4, and ARF5. Taken together, these results suggest that BFA/M-COPA targets at least ARF1, ARF4, and ARF5; in other words, RTKs require the simultaneous activation of ARF1, ARF4, and ARF5 for their ER export."

Journal • Oncology • EGFR • PDGFRA

Type III aortic arch angulation increases aortic stiffness: Analysis from an ex vivo porcine model. (PubMed, JTCVS Open) - "After that, a thoracic stent-graft (VAMF2626C100TU) was deployed in aortas with adequate proximal landing zone diameters to reach 10% t0 20% oversizing...Type III arch PWV resulted the highest and significantly higher compared with the Type I arch after stent-graft deployment (3.81 ± 0.44 vs 4.03 ± 0.46 m/second; P = .023). Increased aortic arch angulation-as in a Type III arch-is associated with higher aortic PWV and blood pressures and this may negatively influence cardiovascular health."

Journal • Preclinical • Cardiovascular

Potential Therapies and Diagnosis Based on Golgi-targeted Nano Drug Delivery Systems. (PubMed, Pharmacol Res) - "In this review, Golgi-targeted NDDSs and their applications in disease therapies and diagnosis such as cancer, metastasis, fibrosis and neurological diseases are introduced. Meanwhile, modifications of NDDSs to achieve targeting strategies, Golgi-disturbing agents to change the morphology of GA, special endocytosis to achieve endosomal/lysosomal escape strategies are also involved."

Journal • Review • CNS Disorders • Fibrosis • Immunology • Oncology

"Meanwhile roche passes on advancing AMF26 $AFMD despite early good data due to competition in bcma 🤦🏻‍♂️" (@Raddinero)

Oncogenic kit signalling on the golgi is suppressed by blocking secretory trafficking with M-COPA in gastrointestinal stromal tumours. (PubMed, Cancer Lett) - "In this study, we show that in GIST, 2-methylcoprophilinamide (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic signalling. Importantly, M-COPA can inhibit the activation of the Kit kinase domain mutant, resulting in suppression of imatinib-resistant GIST proliferation. Our study demonstrates that Kit autophosphorylation is spatio-temporally regulated and may offer a new strategy for treating imatinib-resistant GISTs."

Journal • Biosimilar • Gastrointestinal Cancer • Oncology • Sarcoma

Potential antitumor effects of a Golgi disrupting agent, M-COPA, via targeting cell-extracellular matrix interaction under the spheroid culture conditions (AACR 2019) - "...We previously demonstrated that a Golgi disrupting agent, 2-methylcoprophilinamide (M-COPA), exhibited antitumor effect in human cancer cells in vitro and in vivo; however, in vivo antitumor efficacy of M-COPA did not simply reflect its in vitro efficacy, probably due to the lack of microenvironmental features of tumor tissues in the monolayer culture conditions...Moreover, expression knockdown or neutralizing antibody of the integrins clearly suppressed sphere formation of MKN1 cells. These results suggest that M-COPA exerted in vivo antitumor effects via targeting specific integrins that mediate cell-matrix adhesion and its downstream intracellular signaling pathway observed in 3D spheroid culture models."

Preclinical