TY - JOUR
T1 - Ligandomics
T2 - a paradigm shift in biological drug discovery
AU - Li, Wei
AU - Pang, Iok Hou
AU - Pacheco, Mario Thiego F.
AU - Tian, Hong
N1 - Funding Information:
The safety of anti-Scg3 therapy is supported by Scg3-knockout mice. Mice with homozygous deletion of the Scg3 gene (i.e., equivalent to 100% depletion of Scg3) have a normal phenotype [40] . By contrast, mice with deletion of a single VEGF allele are embryonic lethal with severe defects in blood vessel formation and developmental abnormalities [41] , highlighting the critical role of VEGF in vasculogenesis and embryogenesis. The safety concerns have so far precluded VEGF inhibitors from receiving regulatory approval for ROP therapy in preterm infants. These differential phenotypes of Scg3 −/− and VEGF −/+ mice support the safety of anti-Scg3 mAb for ROP therapy [40,41] . This safety advantage is yet to be confirmed with an anti-Scg3 mAb in preclinical and clinical studies.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/3
Y1 - 2018/3
N2 - As productivity of pharmaceutical research and development (R&D) for small-molecule drugs declines, the trend in drug discovery strategies is shifting towards biologics, which predominantly target secreted or cell surface proteins. Receptors and ligands are the most-valuable drug targets. In contrast to conventional approaches of discovering one ligand at a time, the emerging technology of ligandomics can systematically map disease-selective cellular ligands in the absence of molecular probes. Biologics targeting these ligands with disease selectivity have the advantages of high efficacy, minimal adverse effects, wide therapeutic indices, and low safety-related attrition rates. Therefore, ligandomics represents a paradigm shift to address the bottleneck of target discovery for biologics development.
AB - As productivity of pharmaceutical research and development (R&D) for small-molecule drugs declines, the trend in drug discovery strategies is shifting towards biologics, which predominantly target secreted or cell surface proteins. Receptors and ligands are the most-valuable drug targets. In contrast to conventional approaches of discovering one ligand at a time, the emerging technology of ligandomics can systematically map disease-selective cellular ligands in the absence of molecular probes. Biologics targeting these ligands with disease selectivity have the advantages of high efficacy, minimal adverse effects, wide therapeutic indices, and low safety-related attrition rates. Therefore, ligandomics represents a paradigm shift to address the bottleneck of target discovery for biologics development.
UR - http://www.scopus.com/inward/record.url?scp=85040587109&partnerID=8YFLogxK
U2 - 10.1016/j.drudis.2018.01.013
DO - 10.1016/j.drudis.2018.01.013
M3 - Review article
C2 - 29326083
AN - SCOPUS:85040587109
SN - 1359-6446
VL - 23
SP - 636
EP - 643
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 3
ER -