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: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
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
Introduction: Adrenomedullin (AM) is a peptide responsible for many physiological processes including vascular health and hormone regulation. Dysregulation of AM signaling can stimulate cancers by promoting proliferation, angiogenesis and metastasis. Two AM receptors contribute to tumor progression in different ways. Adrenomedullin-1 receptor (AMR) regulates blood pressure and blocking AM signaling via AMR would be clinically unacceptable. Therefore, antagonizing adrenomedullin-2 receptor (AMR) presents as an avenue for anti-cancer drug development.
Areas Covered: We review the literature to highlight AM's role in cancer as well as delineating the specific roles AMR and AMR mediate in the development of a pro-tumoral microenvironment. We highlight the importance of exploring the residue differences between the receptors that led to the development of first-in-class selective AMR small molecule antagonists. We also summarize the current approaches targeting AM and its receptors, their anti-tumor effects and their limitations.
Expert Opinion: As tool compounds, AMR antagonists will allow the dissection of the functions of CGRPR (calcitonin gene-related peptide receptor), AMR and AMR, and has considerable potential as a first-in-class oncology therapy. Furthermore, the lack of detectable side effects and good drug-like pharmacokinetic properties of these AMR antagonists support the promise of this class of compounds as potential anti-cancer therapeutics.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1080/17460441.2022.2090541 | DOI Listing |
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