دورية أكاديمية
Discovery of CDC42 Inhibitors with a Favorable Pharmacokinetic Profile and Anticancer In Vivo Efficacy.
| العنوان: | Discovery of CDC42 Inhibitors with a Favorable Pharmacokinetic Profile and Anticancer In Vivo Efficacy. |
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| المؤلفون: | Brindani, Nicoletta, Vuong, Linh M, La Serra, Maria Antonietta, Salvador, Noel, Menichetti, Andrea, Acquistapace, Isabella Maria, Ortega, Jose Antonio, Veronesi, Marina, Bertozzi, Sine Mandrup, Summa, Maria, Girotto, Stefania, Bertorelli, Rosalia, Armirotti, Andrea, Ganesan, Anand K, De Vivo, Marco |
| المصدر: | J Med Chem ; ISSN:1520-4804 ; Volume:67 ; Issue:12 |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2024 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | We previously reported trisubstituted pyrimidine lead compounds, namely, ARN22089 and ARN25062, which block the interaction between CDC42 with its specific downstream effector, a PAK protein. This interaction is crucial for the progression of multiple tumor types. Such inhibitors showed anticancer efficacy in vivo. Here, we describe a second class of CDC42 inhibitors with favorable drug-like properties. Out of the 25 compounds here reported, compound 15 (ARN25499) stands out as the best lead compound with an improved pharmacokinetic profile, increased bioavailability, and efficacy in an in vivo PDX tumor mouse model. Our results indicate that these CDC42 inhibitors represent a promising chemical class toward the discovery of anticancer drugs, with ARN25499 as an additional lead candidate for preclinical development. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1021/acs.jmedchem.4c00855Test; https://pubmed.ncbi.nlm.nih.gov/38866385Test |
| DOI: | 10.1021/acs.jmedchem.4c00855 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.4c00855Test https://pubmed.ncbi.nlm.nih.gov/38866385Test |
| رقم الانضمام: | edsbas.FCCC4F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.4c00855 |
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