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Start Over Author "Sun, Chengzao" Journal journal of medicinal chemistry
5 results on '"Sun, Chengzao"'

1. Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Nav1.7 for the Treatment of Pain

Author

Adams, Gregory L., primary, Pall, Parul S., additional, Grauer, Steven M., additional, Zhou, Xiaoping, additional, Ballard, Jeanine E., additional, Vavrek, Marissa, additional, Kraus, Richard L., additional, Morissette, Pierre, additional, Li, Nianyu, additional, Colarusso, Stefania, additional, Bianchi, Elisabetta, additional, Palani, Anandan, additional, Klein, Rebecca, additional, John, Christopher T., additional, Wang, Deping, additional, Tudor, Matthew, additional, Nolting, Andrew F., additional, Biba, Mirlinda, additional, Nowak, Timothy, additional, Makarov, Alexey A., additional, Reibarkh, Mikhail, additional, Buevich, Alexei V., additional, Zhong, Wendy, additional, Regalado, Erik L., additional, Wang, Xiao, additional, Gao, Qi, additional, Shahripour, Aurash, additional, Zhu, Yuping, additional, de Simone, Daniele, additional, Frattarelli, Tommaso, additional, Pasquini, Nicolo’ Maria, additional, Magotti, Paola, additional, Iaccarino, Roberto, additional, Li, Yuxing, additional, Solly, Kelli, additional, Lee, Keun-Joong, additional, Wang, Weixun, additional, Chen, Feifei, additional, Zeng, Haoyu, additional, Wang, Jixin, additional, Regan, Hilary, additional, Amin, Rupesh P., additional, Regan, Christopher P., additional, Burgey, Christopher S., additional, Henze, Darrell A., additional, Sun, Chengzao, additional, and Tellers, David M., additional

Published
2021
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4. Bifunctional PEGylated Exenatide-AmylinomimeticHybridsto Treat Metabolic Disorders: An Example of Long-Acting Dual HormonalTherapeutics.

Author

Sun, Chengzao, Trevaskis, James L., Jodka, Carolyn M., Neravetla, Swetha, Griffin, Pete, Xu, Kui, Wang, Yan, Parkes, David G., Forood, Bruce, and Ghosh, Soumitra S.

Subjects
*EXENATIDE, *METABOLIC disorder treatment, *PEPTIDE hormones, *PHARMACOLOGY, *DRUG efficacy, *WEIGHT loss
Abstract

Peptide hybrids (phybrids) comprisingcovalently linked peptidehormones can leverage independent biological pathways for additiveor synergistic metabolic benefits. PEGylation of biologics offersenhanced stability, duration, and reduced immunogenicity. These twomodalities can be combined to produce long-acting therapeutics withdual pharmacology and enhanced efficacy. Compound 10iscomposed of an exenatide (AC2993) analogue, AC3174, and an amylinomimetic,davalintide (AC2307), with an intervening 40 kD PEG moiety. It displayeddose-dependent and prolonged efficacy for glucose control and bodyweight reduction in rodents with superior in vitroand in vivoactivities compared to those of a side-chainPEGylated phybrid 6. In diet-induced obese (DIO) rats,the weight-loss efficacy of 10was similar to that ofa combination of PEG-parents 3and 4. Asingle dose of 10elicited sustained body weight reductionin DIO rats for at least 21 days. Compound 10’sterminal half-life of ∼27 h should translate favorably to weeklydosing in humans. [ABSTRACT FROM AUTHOR]

Published
2013
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5. Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Na v 1.7 for the Treatment of Pain.

Author

Adams GL, Pall PS, Grauer SM, Zhou X, Ballard JE, Vavrek M, Kraus RL, Morissette P, Li N, Colarusso S, Bianchi E, Palani A, Klein R, John CT, Wang D, Tudor M, Nolting AF, Biba M, Nowak T, Makarov AA, Reibarkh M, Buevich AV, Zhong W, Regalado EL, Wang X, Gao Q, Shahripour A, Zhu Y, de Simone D, Frattarelli T, Pasquini NM, Magotti P, Iaccarino R, Li Y, Solly K, Lee KJ, Wang W, Chen F, Zeng H, Wang J, Regan H, Amin RP, Regan CP, Burgey CS, Henze DA, Sun C, and Tellers DM

Subjects
Animals, Cell Degranulation drug effects, Cystine chemistry, Drug Design, Hot Temperature, Mast Cells drug effects, Models, Molecular, Pain Measurement drug effects, Rats, Spider Venoms pharmacology, NAV1.7 Voltage-Gated Sodium Channel drug effects, Pain drug therapy, Sodium Channel Blockers chemical synthesis, Sodium Channel Blockers pharmacology, Spider Venoms chemical synthesis
Abstract

Inhibitor cystine knot peptides, derived from venom, have evolved to block ion channel function but are often toxic when dosed at pharmacologically relevant levels in vivo . The article describes the design of analogues of ProTx-II that safely display systemic in vivo blocking of Na v 1.7, resulting in a latency of response to thermal stimuli in rodents. The new designs achieve a better in vivo profile by improving ion channel selectivity and limiting the ability of the peptides to cause mast cell degranulation. The design rationale, structural modeling, in vitro profiles, and rat tail flick outcomes are disclosed and discussed.

Published
2022
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