{"id":1905,"date":"2026-05-06T19:12:07","date_gmt":"2026-05-06T17:12:07","guid":{"rendered":"https:\/\/sites.unica.it\/pe2026\/?p=1905"},"modified":"2026-05-06T19:24:48","modified_gmt":"2026-05-06T17:24:48","slug":"lorenzo-raffellini","status":"publish","type":"post","link":"https:\/\/sites.unica.it\/pe2026\/2026\/05\/06\/lorenzo-raffellini\/","title":{"rendered":"Lorenzo Raffellini"},"content":{"rendered":"\n
\n\n\n\n
\"\"<\/figure>
\n

PE Award 9 – Lorenzo Raffellini<\/strong><\/p>\n\n\n\n

University of Pisa, Italy<\/p>\n\n\n\n

e-mail<\/a> – LinkedIn<\/a><\/strong> –<\/strong> ORCID<\/a><\/strong><\/p>\n<\/div><\/div>\n\n\n\n

Targeting autophagy through ampk: design, synthesis, and biological evaluation of novel allosteric modulators<\/strong><\/td><\/tr>
Lorenzo Raffellini1<\/sup>, Roberta Rocca2<\/sup>, Clementina Manera1<\/sup>, Sheraz Gul3<\/sup>, Stefano Alcaro2<\/sup>, Simona Rapposelli1<\/sup>
<\/em>
1<\/sup><\/em> Department of Pharmacy, University of Pisa, Pisa, Italy.
2<\/sup><\/em> Department of Health Science, “Magna Gr\u00e6cia” University of Catanzaro, Catanzaro, Italy.
3<\/sup><\/em> Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackernburgallee 114, 22525 Hamburg, Germany.<\/td><\/tr>
Abstract<\/strong>
MP-activated protein kinase (AMPK) is a heterotrimeric serine\/threonine kinase that serves as a central regulator of cellular energy homeostasis. Sensitive to fluctuations in intracellular AMP\/ATP ratios, AMPK orchestrates a metabolic shift by promoting catabolic processes and inhibiting anabolic ones under energy-deprived conditions [1]. Among the various catabolic pathways regulated by AMPK, autophagy stands out as a pivotal mechanism for maintaining cellular homeostasis. This tightly regulated process of self-digestion ensures cellular survival by recycling damaged organelles and misfolded proteins, particularly under stress conditions such as nutrient deprivation, oxidative stress, or mitochondrial dysfunction [2]. Given its fundamental role in maintaining cellular homeostasis and integrity, impaired autophagy has been linked to the pathogenesis of diverse illnesses, including neuromuscular disorders, metabolic syndrome, and neurodegenerative diseases [3]. As such, pharmacological modulation of AMPK represents a promising strategy to restore autophagic flux and rescue tissue homeostasis to counteract disease progression. In light of the above, we designed a small library of benzimidazole-based derivatives capable of interacting with the allosteric drug and metabolite (ADaM) pocket of AMPK. After in-silico<\/em> evaluation of the proposed structures through a docking study, we synthesized three series of potential ADaM binders. These novel compounds were then tested for their early-ADME-Tox and ecotox properties, with the aim of selecting the most promising ones for progression. Moreover, an in-vitro<\/em> assay was performed to evaluate their potential to activate AMPK (Figure 1<\/strong>).
\"\"
Figure 1. <\/strong>Workflow schematization.<\/td><\/tr>
References \u00a0<\/strong>
[1] Hardie, D.G.; AMP-activated\/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol<\/em> 2007<\/strong>, 8<\/em>, 774-785.
[2] Glick, D., Barth, S. & Macleod, K. F. Autophagy: cellular and molecular mechanisms. The Journal of Pathology <\/em>2010<\/strong>, 221<\/em>, 3-12.
[3] Ichimiya T., Yamakawa T., Autophagy and Autophagy-Related Diseases: A Review. IJMS <\/em>2020<\/strong>, 21<\/em>, 8974.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

PE Award 9 – Lorenzo Raffellini University of Pisa, Italy e-mail – LinkedIn – ORCID Targeting autophagy through ampk: design, synthesis, and biological evaluation of novel allosteric modulators Lorenzo Raffellini1, Roberta Rocca2, Clementina Manera1, Sheraz Gul3, […]<\/p>\n","protected":false},"author":9643,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1905","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1905","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/9643"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=1905"}],"version-history":[{"count":3,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1905\/revisions"}],"predecessor-version":[{"id":1921,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/1905\/revisions\/1921"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=1905"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=1905"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=1905"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}