| Naslov: | New inhibitors of cathepsin V impair tumor cell proliferation and elastin degradation and increase immune cell cytotoxicity |
|---|
| Avtorji: | ID Mitrović, Ana, Institut "Jožef Stefan" (Avtor)
ID Senjor, Emanuela, Institut "Jožef Stefan" (Avtor)
ID Jukič, Marko (Avtor)
ID Bolčina, Lara, Institut "Jožef Stefan" (Avtor)
ID Prunk, Mateja, Institut "Jožef Stefan" (Avtor)
ID Proj, Matic (Avtor)
ID Perišić, Milica, Institut "Jožef Stefan" (Avtor)
ID Gobec, Stanislav (Avtor)
ID Kos, Janko, Institut "Jožef Stefan" (Avtor) |
|---|
| Datoteke: |  URL - Izvorni URL, za dostop obiščite https://www.sciencedirect.com/science/article/pii/S2001037022003804
 PDF - Predstavitvena datoteka, prenos (8,63 MB)
MD5: E48CFC3ECF1AA9C72B9F413A8EC5EB96
|
|---|
| Jezik: | Angleški jezik |
|---|
| Tipologija: | 1.01 - Izvirni znanstveni članek |
|---|
| Organizacija: |  IJS - Institut Jožef Stefan
|
|---|
| Povzetek: | Cathepsin V is a human lysosomal cysteine peptidase with specific functions during pathological processes and is as such a promising therapeutic target. Peptidase inhibitors represent powerful pharmacological tools for regulating excessive proteolytic activity in various diseases. Cathepsin V is highly related to cathepsin L but differs in tissue distribution, binding site morphology, substrate specificity, and function. To validate its therapeutic potential and extend the number of potent and selective cathepsin V inhibitors, we used virtual high-throughput screening of commercially available compound libraries followed by an evaluation of kinetic properties to identify novel potent and selective cathepsin V inhibitors. We identified the ureido methylpiperidine carboxylate derivative, compound 7, as a reversible, selective, and potent inhibitor of cathepsin V. It also exhibited the most preferable characteristics for further evaluation with in vitro functional assays that simulate the processes in which cathepsin V is known to play an important role. Compound 7 exerted significant effects on cell proliferation, elastin degradation, and immune cell cytotoxicity. The latter was increased because compound 7 impaired conversion of immunosuppressive factor cystatin F to its active monomeric form. Taken together, our results present novel potent inhibitors of cathepsin V and provide new hit compounds for detailed development and optimization. Further, we demonstrate that cathepsin V is a potential target for new approaches to cancer therapy. |
|---|
| Status publikacije: | Objavljeno |
|---|
| Verzija publikacije: | Objavljena publikacija |
|---|
| Poslano v recenzijo: | 20.05.2022 |
|---|
| Datum sprejetja članka: | 20.08.2022 |
|---|
| Datum objave: | 28.08.2022 |
|---|
| Založnik: | Elsevier |
|---|
| Leto izida: | 2022 |
|---|
| Št. strani: | str. 4667-4687 |
|---|
| Številčenje: | Vol. 20 |
|---|
| Izvor: | Nizozemska |
|---|
| PID: | 20.500.12556/DiRROS-23485  |
|---|
| UDK: | 577 |
|---|
| ISSN pri članku: | 2001-0370 |
|---|
| DOI: | 10.1016/j.csbj.2022.08.046 |
|---|
| COBISS.SI-ID: | 119687939 |
|---|
| Avtorske pravice: | © 2022 The Author(s). |
|---|
| Datum objave v DiRROS: | 04.09.2025 |
|---|
| Število ogledov: | 255 |
|---|
| Število prenosov: | 166 |
|---|
| Metapodatki: |    |
|---|
|
:
|
Kopiraj citat |
|---|
| | | | Objavi na: |  |
|---|
Postavite miškin kazalec na naslov za izpis povzetka. Klik na naslov izpiše
podrobnosti ali sproži prenos. |
