ATP-competitive inhibitors for cancer treatment – kinases and the world beyond

Jug, Ana (avtor), Ilaš, Janez (avtor)

Adenosine 5′-(tetrahydrogen triphosphate) (ATP), an essential molecule for cellular energy transfer, plays a crucial role in various biochemical processes, including protein folding, DNA repair and intracellular signalling. A promising strategy for the development of anticancer therapies is to target ATP-binding sites of proteins involved in these processes with ATP-competitive inhibitors. They either mimic ATP to block its binding or bind allosterically to induce conformational changes that prevent ATP interaction. While protein kinases are the main focus of ATP-competitive inhibitors used in cancer therapy, other non-kinase targets such as Hsp90, Topo II, p97, RNA helicases and ABC transporters are also recognized as important molecular targets. Their inhibition can overcome resistance to kinase inhibitors, which develops due to mutations in kinase domains, and at the same time alter essential properties of cancer cells. Although they target different protein families, selectivity remains a challenge due to the conserved nature of ATP binding sites. However, the structural differences between the target proteins allow the development of specific inhibitors. In addition, dual inhibitors targeting multiple ATP-dependent proteins can increase therapeutic efficacy, reduce drug resistance and minimize side effects. Several ATP-competitive kinase inhibitors are already approved for clinical use and many more are in clinical trials, demonstrating their potential in cancer therapy. In this review, we focus on ATP-competitive inhibition in cancer therapy beyond kinases, highlighting recent advances and challenges in the field while applying lessons learned from the development of kinase inhibitors.

• Jezik: Angleški jezik
• Ključne besede: protein kinase inhibitors, cancer treatment, pharmaceutical chemistry, cancer, medicine
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: Str. 4044-4067
• Številčenje: Vol. 16, iss. 9
• PID: 20.500.12556/RUL-178382
• UDK: 615.4:54:616-006
• ISSN pri članku: 2632-8682
• DOI: 10.1039/D5MD00235D
• COBISS.SI-ID: 250742787
• Datum objave v RUL: 26.01.2026

Gradivo je del revije

• Naslov: RSC medicinal chemistry
• Skrajšan naslov: RSC med. chem.
• Založnik: Royal Society of Chemistry
• ISSN: 2632-8682
• COBISS.SI-ID: 304960512

Licence

• Licenca: CC BY 3.0, Creative Commons Priznanje avtorstva 3.0 Nedoločena
• Povezava: https://creativecommons.org/licenses/by/3.0/deed.sl
• Opis: Dovoljuje kopiranje in razširjanje vsebin v kakršnemkoli mediju in obliki. Dovoljuje remixanje, urejanje, predelava in vključevanje vsebine v lastna dela v vse namene, tudi komercialne. Primerno morate navesti avtorja, povezavo do licence in označiti spremembe, če so kakšne nastale. To lahko storite na kakršenkoli razumen način, vendar ne na način, ki bi namigoval na to, da dajalec licence podpira vas ali vašo uporabo dela. Ne smete uporabiti pravnih določil ali tehničnih ukrepov, ki bi pravno omejili ali onemogočilo druge, da bi storili karkoli, kar licenca dovoli.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: zaviralci proteinske kinaze, zdravljenje raka, farmacevtska kemija, rak, medicina