Novel approaches for the development of direct KRAS inhibitors: structural insights and drug design
| العنوان: | Novel approaches for the development of direct KRAS inhibitors: structural insights and drug design |
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| المؤلفون: | Kashif Haider, Anku Sharma, M Shahar Yar, Prasanna Anjaneyulu Yakkala, Syed Shafi, Ahmed Kamal |
| المصدر: | Expert Opinion on Drug Discovery. 17:247-257 |
| بيانات النشر: | Informa UK Limited, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Proto-Oncogene Proteins p21(ras), Drug Design, Neoplasms, Mutation, Drug Discovery, Humans, Antineoplastic Agents |
| الوصف: | Hyperactivated RAS signaling is reported in 13% of all human cancers, in which ~80% resulted due to KRAS mutations alone. Direct inhibition of KRAS is an important aspect in treating KRAS-related tumors. Despite the efforts of more than four decades, not many KRAS inhibitors have been successful in obtaining clinical approval, except the very recent FDA approval for sotorasib. In recent years, the understanding of structural insights and allosteric pocket identification at catalytic sites of KRAS are likely to provide an excellent opportunity for the development of much more effective clinical candidates.The presented review article mainly summarizes the developments of small molecule KRAS inhibitors as drug candidates and rational approaches that are being utilized for the selective targeting ofAfter the initial success in targeting the mutant KRAS G12C variants, the search has been shifted to address the challenges concerning the resistance and efficacy of small molecule KRAS inhibitors. However, the contribution of other KRAS mutations at G12V, G13C, and G13D variants causing cancers is much higher than the mutations at G12C. In view of this aspect, specific attention is required to target all other mutations as well. Accordingly, for the development of KRAS targeted therapies, the design of small molecule inhibitors that can inhibit KRAS signaling and as well as target inhibition of other signaling pathways like RAS-SOS and RAS-PI3K has to be explored extensively. |
| تدمد: | 1746-045X 1746-0441 |
| DOI: | 10.1080/17460441.2022.2029842 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2138982c1d1846fbf1d9ddfd9fe9c2dc https://doi.org/10.1080/17460441.2022.2029842 |
| رقم الانضمام: | edsair.doi.dedup.....2138982c1d1846fbf1d9ddfd9fe9c2dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1746045X 17460441 |
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| DOI: | 10.1080/17460441.2022.2029842 |