Targeted therapies for RAS-driven cancers can deliver strong initial responses, but tumors often develop adaptive resistance. SHP2-mediated feedback reactivates the MAPK pathway, undermining treatment response and driving disease recurrence. I-0436650 emerged as a potent, selective, and orally bioavailable allosteric SHP2…
From Hit to Lead: The Chemistry Story Behind IRBM-Z-2 Every successful drug candidate begins with a hit compound and a question: can we make it better? For IRBM's Zika virus antiviral program, that question drove an extensive optimization campaign resulting…
Non-Muscle Invasive Bladder Cancer (NMIBC) and the Challenge of Long-Term Surveillance Non-muscle-invasive bladder cancer (NMIBC) represents around 75% of newly diagnosed bladder cancer cases. Although prognosis at diagnosis is often favorable, recurrence rates remain high, requiring long-term cystoscopic surveillance. This…
Zika Virus as a Therapeutic Target Zika virus (ZIKV) represents a persistent global health threat, particularly due to its association with severe congenital abnormalities including microcephaly in fetuses and neurological disorders such as Guillain-Barré syndrome in adults. Following the 2015…
SHP2 as a Therapeutic Target Src homology phosphotyrosine phosphatase 2 (SHP2), encoded by PTPN11, is a ubiquitously expressed non-receptor protein tyrosine phosphatase. It plays a central role in several signaling pathways, including RAS/MAPK, JAK/STAT, and PI3K/AKT, regulating cell proliferation, differentiation,…
Huntington's disease (HD) is a progressive neurodegenerative disease caused by the expansion of a CAG repeat in the huntingtin (HTT) gene, resulting in a huntingtin protein with an expanded polyglutamine (polyQ) tract. Phosphorylation at residue S421 (pS421) affects HTT biology,…
Unlocking New Avenues for IL-11 Therapeutics Interleukin-11 (IL-11), a member of the cytokine family, has been implicated in various disease pathologies, including pulmonary, hepatic, cardiovascular, renal, and intestinal disorders, as well as oncogenesis. Given its pro-inflammatory and pro-fibrotic roles, IL-11…
Ultra-sensitive tandem mass spectrometry-based assay development and validation The article, "LC-MS/MS Assay for Heparan-N-Sulphatase in Pediatric CSF: A Potential Pharmacodynamic Biomarker for Mucopolysaccharidosis Type IIIA Therapy," published in Clinica Chimica Acta, covers the development, optimization, and qualification of a highly…
Petrocchi, A., & Ciammaichella, A. (2024). A patent review of SHP2 allosteric inhibitors (2018-present). Expert Opinion on Therapeutic Patents, 34(5), 383–396. https://doi.org/10.1080/13543776.2024.2365410 The presence of over 100 patents on SHP2 inhibitors underscores the target's importance and potential impact in drug discovery and…
Simona Ponzi, Federica Ferrigno, Monica Bisbocci, Cristina Alli, Jesus M. Ontoria, Alessia Petrocchi, Carlo Toniatti, Esther Torrente, Direct-to-biology platform: From synthesis to biological evaluation of SHP2 allosteric inhibitors, Bioorganic & Medicinal Chemistry Letters, Volume 100, 2024