Abstract：
:Determining the aggregation propensity of protein-based biotherapeutics is an important step in the drug development process. Typically, a great deal of data collected over a large period of time is needed to estimate the aggregation propensity of biotherapeutics. Thus, candidates cannot be screened early on for aggregation propensity, but early screening is desirable to help streamline drug development. Here, we present a simple molecular computational method to predict the aggregation propensity via hydrophobic interactions, thought to be the most common mechanism of aggregation, and electrostatic interactions. This method uses a new quantity termed Developability Index. It is a function of an antibody's net charge, calculated on the full-length antibody structure, and the spatial aggregation propensity, calculated on the complementarity-determining region structure. Its accuracy is due to the molecular level details and the incorporation of the tertiary structure of the antibody. It is particularly applicable to antibodies or other proteins for which structures are available or could be determined accurately using homology modeling. Applications include the selection of molecules in the discovery or early development process, selection of mutants for stability, and estimation of resources needed for development of a given biomolecule.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Lauer TM,Agrawal NJ,Chennamsetty N,Egodage K,Helk B,Trout BLdoi
10.1002/jps.22758subject
Has Abstractpub_date
2012-01-01 00:00:00pages
102-15issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(15)31778-0journal_volume
101pub_type
杂志文章abstract：:The influence of various test meals and coadministered water volumes on erythromycin stearate bioavailability from orally dosed film-coated tablets was studied in healthy human subjects. Serum erythromycin levels were uniformly reduced by all test meals, with the reduction in mean peak serum levels varying from 47 to ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600670608
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600670319
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600650720
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600641229
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更新日期：2011-05-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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abstract：:To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...
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更新日期：2014-10-01 00:00:00
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600700908
更新日期：1981-09-01 00:00:00
abstract：:The objective of the current study was to develop and evaluate VLDL-resembling phospholipid-submicron emulsion (PSME) as a carrier system for new cholesterol-based compounds for targeted delivery to cancer cells. BCH, a boronated cholesterol compound, was originally developed in our laboratory to mimic the cholesterol...
journal_title：Journal of pharmaceutical sciences
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