scholarly journals Site-Specific PEGylation Enhances the Pharmacokinetic Properties and Antitumor Activity of Interferon Beta-1b

2013 ◽  
Vol 33 (12) ◽  
pp. 769-777 ◽  
Author(s):  
Ji I. Lee ◽  
Stephen P. Eisenberg ◽  
Mary S. Rosendahl ◽  
Elizabeth A. Chlipala ◽  
Jacquelyn D. Brown ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Interferon Beta ◽  
Site Specific ◽  
Pharmacokinetic Properties

ADAPTING PHARMACOKINETIC PROPERTIES OF A HUMANIZED ANTI-INTERLEUKIN-8 ANTIBODY FOR THERAPEUTIC APPLICATIONS USING SITE-SPECIFIC PEGYLATION

Cytokine ◽  
2001 ◽  
Vol 16 (3) ◽  
pp. 106-119 ◽  
Author(s):  
Steven R. Leong ◽  
Laura DeForge ◽  
Leonard Presta ◽  
Tania Gonzalez ◽  
Audrey Fan ◽  
...  
Keyword(s):  
Interleukin 8 ◽  
Site Specific ◽  
Therapeutic Applications ◽  
Pharmacokinetic Properties

Discovery of a Potent Class I Selective Ketone Histone Deacetylase Inhibitor with Antitumor Activity in Vivo and Optimized Pharmacokinetic Properties

2009 ◽  
Vol 52 (11) ◽  
pp. 3453-3456 ◽  
Author(s):  
Olaf Kinzel ◽  
Laura Llauger-Bufi ◽  
Giovanna Pescatore ◽  
Michael Rowley ◽  
Carsten Schultz-Fademrecht ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Class I ◽  
Deacetylase Inhibitor ◽  
Pharmacokinetic Properties

scholarly journals Tailoring structure-function and pharmacokinetic properties of single-chain Fv proteins by site-specific PEGylation

2003 ◽  
Vol 16 (10) ◽  
pp. 761-770 ◽  
Author(s):  
K. Yang ◽  
A. Basu ◽  
M. Wang ◽  
R. Chintala ◽  
M.-C. Hsieh ◽  
...  
Keyword(s):  
Structure Function ◽  
Single Chain ◽  
Site Specific ◽  
Single Chain Fv ◽  
Pharmacokinetic Properties

scholarly journals Site-specific PEGylation endows a mammalian ribonuclease with antitumor activity

2011 ◽  
Vol 12 (3) ◽  
pp. 208-214 ◽  
Author(s):  
Thomas J. Rutkoski ◽  
John A. Kink ◽  
Laura E. Strong ◽  
Ronald T. Raines
Keyword(s):  
Antitumor Activity ◽  
Site Specific

scholarly journals Site-Specific PEGylation of Anti-Mesothelin Recombinant Immunotoxins Increases Half-life and Antitumor Activity

2019 ◽  
Vol 19 (3) ◽  
pp. 812-821 ◽  
Author(s):  
Zeliang Zheng ◽  
Ryuhei Okada ◽  
Hisataka Kobayashi ◽  
Tadanobu Nagaya ◽  
Junxia Wei ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Half Life ◽  
Site Specific ◽  
Recombinant Immunotoxins

scholarly journals Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life

ACS Omega ◽  
2020 ◽  
Vol 5 (31) ◽  
pp. 19778-19784
Author(s):  
Tae Yoon Kim ◽  
You Ree Nam ◽  
Jin Ho Park ◽  
Dong-Eun Lee ◽  
Hak-Sung Kim
Keyword(s):  
Antitumor Activity ◽  
Half Life ◽  
Site Specific

scholarly journals Antitumor Activity of Ribonuclease Multimers Created by Site-Specific Covalent Tethering

2010 ◽  
Vol 21 (9) ◽  
pp. 1691-1702 ◽  
Author(s):  
Thomas J. Rutkoski ◽  
John A. Kink ◽  
Laura E. Strong ◽  
Christine I. Schilling ◽  
Ronald T. Raines
Keyword(s):  
Antitumor Activity ◽  
Site Specific

scholarly journals Site-specific incorporation of 5′-methyl DNA enhances the therapeutic profile of gapmer ASOs

2021 ◽  
Vol 49 (4) ◽  
pp. 1828-1839 ◽  
Author(s):  
Guillermo Vasquez ◽  
Graeme C Freestone ◽  
W Brad Wan ◽  
Audrey Low ◽  
Cheryl Li De Hoyos ◽  
...  
Keyword(s):  
Structural Changes ◽  
Therapeutic Potential ◽  
Therapeutic Index ◽  
Site Specific ◽  
New Era ◽  
Nucleic Acid Analogs ◽  
Pharmacokinetic Properties ◽  
Dna Modifications ◽  
Therapeutic Properties ◽  
Therapeutic Profile

Abstract We recently showed that site-specific incorporation of 2′-modifications or neutral linkages in the oligo-deoxynucleotide gap region of toxic phosphorothioate (PS) gapmer ASOs can enhance therapeutic index and safety. In this manuscript, we determined if introducing substitution at the 5′-position of deoxynucleotide monomers in the gap can also enhance therapeutic index. Introducing R- or S-configured 5′-Me DNA at positions 3 and 4 in the oligodeoxynucleotide gap enhanced the therapeutic profile of the modified ASOs suggesting a different positional preference as compared to the 2′-OMe gap modification strategy. The generality of these observations was demonstrated by evaluating R-5′-Me and R-5′-Ethyl DNA modifications in multiple ASOs targeting HDAC2, FXI and Dynamin2 mRNA in the liver. The current work adds to a growing body of evidence that small structural changes can modulate the therapeutic properties of PS ASOs and ushers a new era of chemical optimization with a focus on enhancing the therapeutic profile as opposed to nuclease stability, RNA-affinity and pharmacokinetic properties. The 5′-methyl DNA modified ASOs exhibited excellent safety and antisense activity in mice highlighting the therapeutic potential of this class of nucleic acid analogs for next generation ASO designs.

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