University of South Florida

The Penn State Research Foundation

H. Lee Moffitt Cancer Center and Research Institute, Inc.

Hong-Gang Wang

Roman Manetsch

Domenico Coppola

David Lawrence Flanigan

Megan M Barber

Jeremiah Dwayne Tipton

Niranjan Kumar Namelikonda

Katya Pavlova Nacheva

Kenichiro Doi

Xiangdong Hu

Sameer Kulkarni

Iredia David Iyamu

Jiazhi Sun

Sameer Shamrao Kulkarni

Methods of identifying target binding molecules by target guided synthesis are provided. The methods include providing two or more fragments capable of reacting to form the target binding molecule and mixing the fragments with the target. The methods can be used to identify target binding molecules that bind targets such as proteins or nucleic acids, including those that bind shallow binding pockets on the surface of such targets. The methods are applied to the Bcl-XL and Mcl-1 proteins from the Bcl-2 family of proteins. Using thio acid and sulfonyl azide fragments capable of reacting through sulfo-click chemistry, new acyl sulfonamides are identified that bind one or both of the Bcl-XL and Mcl-1 proteins. Pharmaceutical formulations of these target binding molecules are also provided.

Target binding molecules identified by kinetic target-guided synthesis

The present disclosure relates to acylsulfonamides and processes for their preparation. The processes involve a target-guided synthesis approach, whereby a thioacid and a sulfonyl azide are reacted in the presence of a biological target protein, a Bcl-2 family protein, to form the acylsulfonamide.

Acylsulfonamides and processes for producing the same

The invention includes methods for detecting the presence of a neoplastic condition by comparing a sample level of a BIF-1 to a reference, wherein a low level of BIF-1 in the sample correlates with the presence of a neoplastic condition. Another method involves determining the risk of relapse, tumor recurrence and/or metastasis by determining a sample level of a Bif-1 to a reference level of Bif-1, wherein low sample levels correlate with a likelihood of relapse, recurrence and/or metastasis. Yet another method includes detecting the presence of a pre-neoplastic condition, such as prostatic intraepithelial neoplasia. The method involves measuring a level of a Bif-1 in a sample and comparing the level of Bif-1 in the sample to a reference level of Bif-1. High levels of Bif-1 in the sample correlate with the presence of the pre-neoplastic condition.

Method for early detection of cancers

Growing community of inventors

Palmyra, PA, United States of America

Hong-Gang Wang