JOHN JOSEPH TURCHI
Pilots at Pennsylvania St, Indianapolis, IN
License number
Indiana A5288900
Issued Date
Jan 2016
Expiration Date
Jan 2018
Category
Airmen
Type
Authorized Aircraft Instructor
Address
Address
5445 N Pennsylvania St, Indianapolis, IN 46220
Professional information
Small Molecule Inhibitors Of Replication Protein A That Also Act Synergistically With Cisplatin
US Patent:
2014001, Jan 16, 2014
Filed:
Sep 19, 2011
Appl. No.:
13/824318
Inventors:
John J. Turchi - Indianapolis IN, US
Richard Fitch - Terre Haute IN, US
Richard Fitch - Terre Haute IN, US
Assignee:
INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORP. - Indianapolis IN
International Classification:
A61K 31/22, A61K 31/343
US Classification:
435375
Abstract:
Replication protein A (RPA) is a single-strand DNA-binding protein with essential roles in DNA replication, recombination and repair. Small molecule inhibitors (SMIs) with the ability to disrupt RPA binding activity to ssDNA have been identified and assessed using both lung and ovarian cancer cell lines. Lung cancer cell lines demonstrated increased apoptotic cell death following treatment with the SMI MCI13E, with IC50 values of ˜5 The A2780 ovarian cancer cell line and the p53-null lung cancer cell line HI 299 were particularly sensitive to MCI13E treatment with ICvalues below 3 Sequential treatment with MCI13E and cisplatin resulted in synergism, suggesting that decreasing RPA's DNA binding activity via a SMI may disrupt RPA's role in cell cycle regulation. Thus, RPA SMIs hold the potential to be used as single agent chemotherapeutics or in combination with current chemotherapeutic regimens to increase their efficacy.
Materials And Method For Inhibiting Replication Protein A And Uses Thereof
US Patent:
2013002, Jan 31, 2013
Filed:
Feb 5, 2011
Appl. No.:
13/576023
Inventors:
John J. Turchi - Indianapolis IN, US
Sarah Shuck - Nashville TN, US
Sarah Shuck - Nashville TN, US
Assignee:
INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION - Indianapolis IN
International Classification:
A61K 31/5377, A61K 31/415, A61K 31/4155, A61K 31/4741, A61P 35/00, A61P 31/00, A61K 33/24, A61K 31/7048, C07D 413/14, A61K 31/675, A61K 31/655, A61K 31/7028, A61K 31/4375, A61K 31/4188, G01N 33/566, C12N 5/00, C12N 5/09, A61K 31/4709
US Classification:
424649, 514314, 5142352, 514403, 514406, 514291, 514 27, 544128, 514110, 514151, 514 34, 514283, 514393, 436501, 435375
Abstract:
Targeting uncontrolled cell proliferation and resistance to DNA damaging chemotherapeutics with at least one reagent has significant potential in cancer treatment. Replication Protein A, the eukaryotic single-strand (ss) DNA binding protein, is essential for genomic maintenance and stability via roles in both DNA replication and repair. Reported herein are small molecules that inhibits the in vitro, in vivo, and cellular ssDNA binding activity of RPA, thereby disrupting the eukaryotic cell cycle, inducing cytotoxicity and increasing the efficacy of chemotherapeutic agents damage DNA, and/or disrupt its replication and/or function. These results provide new insights into the mechanism of RPA-ssDNA interactions in chromosome maintenance and stability. This represents a molecularly targeted eukaryotic DNA binding inhibitor and demonstrates the utility of targeting a protein-DNA interaction as a means of studying the cell cycle and providing a therapeutic strategy for cancer treatment.