Severity: Warning
Message: fopen(/var/lib/php/sessions/ci_sessiondhbf3c360u5aeao3a36hrh3c93tv6h0r): Failed to open stream: No space left on device
Filename: drivers/Session_files_driver.php
Line Number: 177
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)
Filename: Session/Session.php
Line Number: 137
Backtrace:
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
Line Number: 71
Backtrace:
File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
Line Number: 8919
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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
The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy toward the inhibition of MYC via the disruption of the protein-protein interaction between MYC and its chromatin cofactor WD Repeat-Containing Protein 5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small-molecule inhibitors of this interaction with potent in vitro binding affinity and report structurally related negative controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors and anticipate that the molecules disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933084 | PMC |
http://dx.doi.org/10.1021/acs.jmedchem.9b01411 | DOI Listing |
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