Qu, Hongchang published the artcileNew analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties, Category: ethers-buliding-blocks, the publication is Immunobiology (2013), 218(4), 496-505, database is CAplus and MEDLINE.
Therapeutic modulation of the complement system has become increasingly important in line with the growing recognition of the role of complement in numerous diseases. Compstatin, a peptidic inhibitor that acts at the central level of the complement cascade, is currently in clin. evaluation but routes to improve its efficacy have not yet been fully explored. Here, we report improvements in both the inhibitory potency and pharmacokinetic parameters of compstatin that broaden its clin. applications. Selective modification of the compstatin N-terminus with non-proteinogenic amino acids resulted in the first analog with subnanomolar binding affinity (KD = 0.5 nM) and other similarly potent derivatives with improved solubility in clin. relevant solvents. Detailed structure-activity relationship studies based on biophys. and computational methods revealed key structural determinants for the observed improvements. Importantly, pharmacokinetic evaluation in non-human primates revealed target-driven elimination kinetics with plasma half-life values exceeding expectations for peptidic drugs (close to 12 h). This successful optimization strategy is expected to pave the way for systemic administration of compstatin in a range of clin. conditions.
Immunobiology published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Category: ethers-buliding-blocks.
Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem