A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Synthesis and biological evaluation of a water-soluble phosphate prodrug salt and structural analogues of KGP94, a lead inhibitor of cathepsin L. | LitMetric

Synthesis and biological evaluation of a water-soluble phosphate prodrug salt and structural analogues of KGP94, a lead inhibitor of cathepsin L.

Bioorg Med Chem Lett

Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798-7348, United States; Institute of Biomedical Studies, Baylor University, One Bear Place #97224, Waco, TX 76798-7224, United States; Mateon Therapeutics, Inc., 701 Gateway Blvd, Suite 210, South San Francisco, CA 94080, United States. Electronic address:

Published: March 2017

AI Article Synopsis

  • * A small-molecule inhibitor called KGP94, and its analogues, have been developed to inhibit cathepsin L effectively, with KGP94 showing an IC value of 189nM.
  • * To improve KGP94's solubility for biological studies, a water-soluble phosphate salt (KGP420) was created, which can easily convert back to KGP94 in the body, as shown by enzymatic studies.

Article Abstract

The magnitude of expression of cathepsin L, often upregulated in the tumor microenvironment, correlates with the invasive and metastatic nature of certain tumors. Inhibition of cathepsin L represents an emerging strategy for the treatment of metastatic cancer. A potent, small-molecule inhibitor (referred to as KGP94) of cathepsin L, and new KGP94 analogues were synthesized. (3,5-Dibromophenyl)-(3-hydroxyphenyl) ketone thiosemicarbazone (22), with an IC value of 202nM, exhibited similar inhibitory activity against cathepsin L compared to KGP94 (IC=189nM). Due to limited aqueous solubility of KGP94, a water-soluble phosphate salt (KGP420) was prepared in order to facilitate future in vivo studies. Enzymatic hydrolysis with alkaline phosphatase (ALP) demonstrated that the phosphate prodrug, KGP420, was readily converted to the parent compound, KGP94.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2016.12.039DOI Listing

Publication Analysis

Top Keywords

water-soluble phosphate
8
phosphate prodrug
8
kgp94
6
cathepsin
5
synthesis biological
4
biological evaluation
4
evaluation water-soluble
4
prodrug salt
4
salt structural
4
structural analogues
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: