Scientific Contributions Archivi

Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design

Scientific Contributions

In the last few years macrocyclic peptides have emerged as a better class of lead candidates for inhibition of protein-protein interactions with respect to conventional small molecules. The IRBM peptide chemistry team collaborated with the teams at Merck & co. and RaPharma to develop potent macrocyclic peptide inhibitors of PCSK9 a key regulator of plasma LDL-cholesterol.

IRBM & collaborators publish on techniques for characterizing peptides in Type 2 diabetes and a peptide drug discovery program for Huntington’s disease

In The News, Scientific Contributions

Nowadays, there is a strong drive to explore new areas of chemical space in search of innovative ways to bind and modulate challenging biological targets. At IRBM our peptide chemistry team has extensive expertise in peptide and macrocyclic drug discovery in various therapeutic areas.

Comparison Of Different Protein Precipitation And Solid‐phase Extraction Protocols For The Study Of The Catabolism Of Peptide Drugs By LC‐HRMS

IRBM publishes in J. Peptide Science on methods to study catabolism, key to designing more stable peptides

Scientific Contributions

IRBM used liquid chromatography-high resolution mass spectrometry to explore different methods for the study of catabolism (breakdown) which is a key driver in the design of more stable peptides.

IRBM & University of Rome publishes in PLOS on new chemotype with antiparasitic activity for treating sleeping sickness

Scientific Contributions

Trypanosoma brucei is a parasite responsible for human African trypanosomiasis, also known as sleeping sickness, a disease endemic in sub-Saharan Africa, with 70 million people at risk of infection. Current treatments are limited by their toxicity, administration in endemic countries and treatment resistance.

IRBM publishes on optimizing a new series of Trypanosoma brucei growth inhibitors, the parasite responsible of the sleeping sickness

Scientific Contributions

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic disease that causes significant mortality in sub- Saharan Africa. A previous publication from IRBM laboratory reported the identification of 2-(1H-imidazo-2-yl)piperazines as a new series of potent T. brucei growth inhibitors.

IRBM & University of Rome publishes in Nature on crucial signaling pathway in muscle homeostasis and regeneration

Scientific Contributions

IRBM, working with the University of Rome’s Department of Biology, examined signaling pathways involved with the regulation of Fibro/Adipogenic Progenitors (FAPs). FAPs are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration.

IRBM’s publishes in Cells on establishing a human blood-brain barrier model for use in drug discovery for neurodegenerative diseases such as Huntington’s

Scientific Contributions

The blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain. It has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to establish in vitro BBB models.

Combined Peptide and Small-Molecule Approach Toward Nonacidic THIQ Inhibitors of the KEAP1/NRF2 Interaction

Scientific Contributions

The NRF2/ARE signalling pathway is a key mediator in oxidative stress and therefore a potential target for neuroprotective agents. The publication describes the identification of nonacidic tetrahydroisoquinolines (THIQs) that inhibit the interaction between NRF2 and its main negative regulator KEAP1.…

IRBM’s Chief Science Officer, Carlo Toniatti is featured in the Medicine Maker’s Power List

In The News, Scientific Contributions

Carlo joins other leading authorities in drug discovery and development as part of the Biopharmaceuticals category in the Medicine Maker Power List. In his interview he reviews future trends in drug development and some of the defining moments of his…

Targeting The HIV-1 Nucleocapsid Protein To Fight Antiretroviral Drug Resistance

Dihydroxypyrimidine Scaffold to Target HIV‑1 Nucleocapsid Protein

In The News, Scientific Contributions

IRBM and their collaborators’ at the universities of Strasbourg and Siena have recently published a paper in the ACS Medicinal Chemistry Letters which describes their approach to the identification of a 5-dihydroxypyrimidine-6-carboxamide substructure as a privileged scaffold of a new…