A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionud87ssi4pdof6v5llfsurtlgmpth7lk9): 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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

A PHP Error was encountered

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

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: 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

Identification and Preclinical Evaluation of the Bicyclic Pyrimidine γ-Secretase Modulator BMS-932481. | LitMetric

AI Article Synopsis

Article Abstract

A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine γ-secretase modulator BMS-932481. The compound showed robust reductions of Aβ and Aβ in the plasma, brain, and cerebrospinal fluid of mice and rats. Consistent with the γ-secretase modulator mechanism, increases in Aβ and Aβ were observed, with no change in the total amount of Aβ produced. No Notch-based toxicity was observed, and the overall preclinical profile of BMS-932481 supported its further evaluation in human clinical trials.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421538PMC
http://dx.doi.org/10.1021/acsmedchemlett.8b00541DOI Listing

Publication Analysis

Top Keywords

γ-secretase modulator
12
bicyclic pyrimidine
8
pyrimidine γ-secretase
8
modulator bms-932481
8
aβ aβ
8
5
identification preclinical
4
preclinical evaluation
4
evaluation bicyclic
4
bms-932481 triazine
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!