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Burns KE , Hensley H , Robinson MK , Thevenin D
Therapeutic Efficacy of a Family of pHLIP-MMAF Conjugates in Cancer Cells and Mouse Models
Mol Pharm. 2017 Feb 6;14(2) :415-422
PMID: 28048942    PMCID: PMC5293657    URL: https://www.ncbi.nlm.nih.gov/pubmed/28048942
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The targeting of therapeutics specifically to diseased tissue is crucial for the development of successful cancer treatments. The approach here is based on the pH(low) insertion peptide (pHLIP) for the delivery of a potent mitotic inhibitor monomethyl auristatin F (MMAF). We investigated six pHLIP variants conjugated to MMAF to compare their efficacy in vitro against cultured cancer cells. While all pHLIP-MMAF conjugates exhibit potent pH- and concentration-dependent killing, their cytotoxicity profiles are remarkably different. We also show that the lead conjugate exhibits significant therapeutic efficacy in mouse models without overt toxicities. This study confirms pHLIP-monomethyl auristatin conjugates as possible new therapeutic options for cancer treatment and supports their further development.
1543-8392 Burns, Kelly E Hensley, Harvey Robinson, Matthew K Thevenin, Damien ORCID: http://orcid.org/0000-0002-1866-0694 R21 CA181868/CA/NCI NIH HHS/United States Journal Article United States Mol Pharm. 2017 Jan 13. doi: 10.1021/acs.molpharmaceut.6b00847.