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10.1073/pnas.1717932115 http://scihub22266oqcxt.onion/10.1073/pnas.1717932115 C5789948!5789948!29279368     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2018 ; 115 (4): E802-11 Nephropedia Template TP {{tp|p=29279368|t=2018. From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection |pdf=|usr=}}{{29279368}} gab.com Text From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=29279368 #FOAvip Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy; however, concerns about poor pharmacological properties, dose restriction because of toxicity, and drug resistance have limited treatment options. Our computational and structure-guided design studies for lead optimization have transformed a 5 µM virtual screening hit into a class of NNRTIs with remarkable potency, safety, drug resistance profile, and pharmacological properties. We report a representative, compound I, with marked synergy with existing HIV-1 drugs and antiviral efficacy in HIV-1?infected humanized mice. A single dose of long-acting nanoformulation of compound I retains sustained levels and efficacy for ?3 weeks, confirming potential as a late-stage preclinical candidate. Additionally, these properties of compound I suggest that it may be a promising candidate to evaluate for preexposure prophylaxis. Twit Text FOAVip From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=29279368 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29279368 #FOAvip English Wikipedia <ref>{{Cite pmid|29279368}}</ref> From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection #MMPMID29279368 Kudalkar SN; Beloor J; Quijano E; Spasov KA; Lee WG; Cisneros JA; Saltzman WM; Kumar P; Jorgensen WL; Anderson KS Proc Natl Acad Sci U S A 2018[Jan]; 115 (4): E802-11 PMID29279368show ga Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy; however, concerns about poor pharmacological properties, dose restriction because of toxicity, and drug resistance have limited treatment options. Our computational and structure-guided design studies for lead optimization have transformed a 5 µM virtual screening hit into a class of NNRTIs with remarkable potency, safety, drug resistance profile, and pharmacological properties. We report a representative, compound I, with marked synergy with existing HIV-1 drugs and antiviral efficacy in HIV-1?infected humanized mice. A single dose of long-acting nanoformulation of compound I retains sustained levels and efficacy for ?3 weeks, confirming potential as a late-stage preclinical candidate. Additionally, these properties of compound I suggest that it may be a promising candidate to evaluate for preexposure prophylaxis. äFrom in silico hit to long-acting late-stage preclinical candidate to (epmc).pdf DeepDyve Pubget Overpricing