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Selective 20S proteasome inhibition for multiple myeloma therapy

Descrizione del progetto

Verso trattamenti più selettivi per il mieloma multiplo

Il mieloma multiplo è la neoplasia ematologica più comune che colpisce le plasmacellule, le cellule che producono anticorpi nel nostro organismo. Gli inibitori del proteasoma sono il trattamento farmacologico di riferimento per il mieloma multiplo, ma sono correlati a un’attività non specifica e a effetti collaterali negativi. Il lavoro del precedente progetto 20SInhibitor, finanziato dall’UE, ha portato alla progettazione di una proteina artificiale basata sulla struttura degli inibitori del proteasoma 20S identificati di recente, ossia i regolatori del «core» catalitico, che mirano selettivamente al proteasoma 20S. Nel complesso, il lavoro dei ricercatori guiderà la progettazione di nuovi inibitori peptidici che mirano specificamente al proteasoma 20S, esibendo una maggiore selettività per le cellule tumorali e meno effetti collaterali sistemici. Durante il progetto 20SInhibitor, i ricercatori si impegneranno in azioni volte a portare la loro innovazione dal laboratorio alla fase successiva nello sviluppo della terapia per il mieloma multiplo.

Obiettivo

Multiple myeloma (MM) is a cancer of plasma cells, that is incurable, and the second most common form of blood cancer. Proteasome inhibitors (PIs) are considered a mainstay in the treatment of MM and mantle cell lymphoma (MCL). Current drugs, based on PIs however, target the chymotrypsin-like activity of the 20S proteasome, and inhibit the activities of both the 20S and 26S proteasomes. Thus, it is possible that selective drug intervention specifically inhibiting only the 20S proteasomes will reduce toxicity, and minimize the deleterious side effects of the current therapeutic regimens.

Our preliminary work revealed a family of 20S proteasome inhibitors, which we termed Catalytic Core Regulators (CCRs) that selectively target the 20S proteasome rather than the 26S complex. Based on sequence motif and structural elements of the CCRs we have designed an artificial protein that is capable of inhibiting the 20S proteasome. We anticipate that these findings will lead to the design of synthetic proteins, peptides or peptidomimetic compounds targeting cancer cells more specifically. This specificity will pose the compounds in an attractive light for using them in various therapeutic applications.

What is exciting from the commercialization perspective, is that pharmaceutical research has switched to revisit the use of peptides as therapeutics. Pharmaceutical companies have seen the development of peptides as a promising direction to lower their risk position. Overall, peptide therapeutics have a 20% chance of receiving regulatory approval, a probability that is 50% higher than that for the approval of small molecules, which form the basis of so called traditional drugs.

In the project, we will carry out actions, which will equip us with the sufficient IP protection strategy, business strategy, industry networks and initial contacts for taking the innovation out from the laboratory to next phase in developing therapy first for MM and MCL later on.

Meccanismo di finanziamento

ERC-POC - Proof of Concept Grant

Istituzione ospitante

WEIZMANN INSTITUTE OF SCIENCE
Contribution nette de l'UE
€ 150 000,00
Indirizzo
HERZL STREET 234
7610001 Rehovot
Israele

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 150 000,00

Beneficiari (1)