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Physicochemical Considerations of Tumor Selective Drug Delivery and Activity Confinement with Particular Reference to 1,2-Bis(Sulfonyl)-1- Alkylhydrazines Delivery

[ Vol. 17 , Issue. 5 ]

Author(s):

Philip Penketh*, Hugh Williamson and Krishnamurthy Shyam   Pages 362 - 374 ( 13 )

Abstract:


Hypoxic tumor cell sub-populations are highly resistant to radiotherapy and their presence frequently causes disease recurrence and death. Here, we described the physicochemical properties required to develop superior tumor-targeted hypoxia-activated modular prodrugs that liberate extremely short-lived bis(sulfonyl)hydrazines (BSHs) as reactive cytotoxins, thereby precisely focusing cytotoxic stress on these radio-resistant hypoxic sub-populations. Therefore, cytotoxic stress will be focused on radiation resistant areas and thus strongly synergizing with radiotherapy.

Keywords:

Hypoxic tumor cell, bis(sulfonyl)hydrazines (BSHs), cytotoxic stress, hypoxic sub-populations, radiotherapy, hypoxic sub-populations.

Affiliation:

Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, BP Exploration, Chertsey Road, Sunbury-on-Thames, Middlesex, TW16 7LN, Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520

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