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1.
Biochem Soc Trans ; 48(1): 271-280, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-31985743

RESUMEN

Fragment-based drug discovery (FBDD) has become a mainstream technology for the identification of chemical hit matter in drug discovery programs. To date, the food and drug administration has approved four drugs, and over forty compounds are in clinical studies that can trace their origins to a fragment-based screen. The challenges associated with implementing an FBDD approach are many and diverse, ranging from the library design to developing methods for identifying weak affinity compounds. In this article, we give an overview of current progress in fragment library design, fragment to lead optimisation and on the advancement in techniques used for screening. Finally, we will comment on the future opportunities and challenges in this field.


Asunto(s)
Diseño de Fármacos , Descubrimiento de Drogas/métodos , Descubrimiento de Drogas/tendencias , Bibliotecas de Moléculas Pequeñas/química , Cristalografía por Rayos X , Aprobación de Drogas , Evaluación Preclínica de Medicamentos/métodos , Ensayos Analíticos de Alto Rendimiento/tendencias , Humanos , Espectroscopía de Resonancia Magnética , Unión Proteica
2.
PLoS One ; 11(11): e0166399, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27902729

RESUMEN

Two markers of regional exchange in the Eastern Mediterranean during the first millennium BCE are the White Painted and Bichrome Wares from Cyprus's Cypro-Geometric and Cypro-Archaic periods. Although these ceramics are often assumed to be imports from Cyprus, excavations in southern Turkey at sites such as Tarsus-Gözlükule, Kilise Tepe, Sirkeli Höyük, and Kinet Höyük suggest that at least some of this pottery was produced locally, requiring a major revision of our understanding of economic interaction in the Eastern Mediterranean. We employ a combination of portable x-ray fluorescence and neutron activation analysis to investigate the White Painted and Bichrome Wares recovered from Tell Tayinat, Çatal Höyük, and Tell Judaidah, three sites in the Amuq Valley of southeastern Anatolia. Our results demonstrate that a clear geochemical distinction exists between imported and local versions of this pottery. Through comparison with legacy datasets, we locate the likely origin of the imported pottery in the Circum-Troodos sediments of central and southern Cyprus. The secondary and tertiary settlements of Çatal Höyük and Tell Judaidah had access only to this imported material. In contrast, the inhabitants of Tell Tayinat, capital city of the region, consumed both imported and locally produced White Painted and Bichrome Wares. This pattern cannot be explained in purely economic terms whereby the frequency of imports decreases as distance from the point of production increases. Instead, we suggest that elite feasting practices drove demand, resulting in either local potters producing Cypriot-style pottery or Cypriot potters settling in the vicinity of Tell Tayinat. These findings offer new insights into the relationship between historically attested Iron Age kingdoms in southern Turkey and Cyprus and complicate our understanding of exchange in the Eastern Mediterranean during the Iron Age.


Asunto(s)
Arqueología/métodos , Cerámica/análisis , Cerámica/química , Factores Socioeconómicos/historia , Chipre , Historia Antigua , Humanos , Análisis de Activación de Neutrones , Espectrometría por Rayos X , Turquía
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