Abstract:
:Collaborations between the pharmaceutical industry and contract research organizations continue to represent an attractive alternative to internal drug discovery within a single organization. This Viewpoint covers many of the business models and strategies that are employed in industry-contract research organization collaborations.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Steadman VAdoi
10.1021/acsmedchemlett.8b00236subject
Has Abstractpub_date
2018-06-04 00:00:00pages
581-583issue
7issn
1948-5875journal_volume
9pub_type
社论abstract::With the COVID-19 pandemic, the evolutionary fate of SARS-CoV-2 becomes a matter of utmost concern. Mutation D614G in the spike (S) protein has become dominant, and recent evidence suggests it yields a more stable phenotype with higher transmission efficacy. We carry out a structural analysis that provides mechanistic...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00410
更新日期:2020-08-17 00:00:00
abstract::[(11)C]N-Methyl lansoprazole ([(11)C]NML, 3) was synthesized and evaluated as a radiopharmaceutical for quantifying tau neurofibrillary tangle (NFT) burden using positron emission tomography (PET) imaging. [(11)C]NML was synthesized from commercially available lansoprazole in 4.6% radiochemical yield (noncorrected RCY...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300216t
更新日期:2012-09-25 00:00:00
abstract::Medicinal chemists have increasing opportunities to transition from the pharmaceutical industry to academic medical centers interested in translational research. This Viewpoint highlights some of the differences between these two cultures and strategies to succeed in academic drug discovery. ...
journal_title:ACS medicinal chemistry letters
pub_type: 社论
doi:10.1021/acsmedchemlett.9b00107
更新日期:2019-04-15 00:00:00
abstract::WaterMap and MM-GB/SA scoring methods were applied to an extensive congeneric series of small-molecule SRC inhibitors with high-quality enzyme data and well characterized binding modes to compare the performance of these scoring methods in this data set and to provide insight into the relative strengths of each method...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml200222u
更新日期:2012-01-06 00:00:00
abstract::The National Institutes of Health (NIH) closure of the agency's Center for Regenerative Medicine (CRM), which focused on therapeutic development of induced pluripotent stem cells (iPS), was caused by the lack of progress in practical development of the iPSs for use in human therapies. As the NIH evaluates priorities i...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500396z
更新日期:2014-10-08 00:00:00
abstract::A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cru...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00336
更新日期:2015-12-15 00:00:00
abstract::Mitragyna speciosa, also known as kratom, has the potential meet the need for pain medications that lack the addictiveness and overdose risk of classical opioid analgesics, such as morphine. This need is urgent because opioid addiction and overdose deaths have risen throughout diverse segments of U.S. society. Some op...
journal_title:ACS medicinal chemistry letters
pub_type: 社论
doi:10.1021/acsmedchemlett.7b00298
更新日期:2017-08-08 00:00:00
abstract::A new subseries of ROMK inhibitors exemplified by 28 has been developed from the initial screening hit 1. The excellent selectivity for ROMK inhibition over related ion channels and pharmacokinetic properties across preclinical species support further preclinical evaluation of 28 as a new mechanism diuretic. Robust ph...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500440u
更新日期:2015-05-07 00:00:00
abstract::The effects of opioids in the central nervous system (CNS) provide significant benefit in the treatment of pain but can also lead to physical dependence and addiction, which has contributed to a growing opioid epidemic in the United States. Gastrointestinal dysfunction is an additional serious consequence of opioid us...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00406
更新日期:2019-11-26 00:00:00
abstract::The natural product L-783277 is a resorcylic lactone type covalent kinase inhibitor. We have prepared the 5'-deoxy analogue of L-783277 (1) in a stereoselective fashion. Remarkably, this analogue retains almost the full kinase inhibitory potential of natural L-783277, with low nanomolar IC50 values against the most se...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml1001807
更新日期:2010-10-20 00:00:00
abstract::A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carbo...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml300396r
更新日期:2013-01-04 00:00:00
abstract::We report a series of lipidated α-AApeptides that mimic the structure and function of natural antimicrobial lipopeptides. Several short lipidated α-AApeptides show broad-spectrum activity against a range of clinically related Gram-positive and Gram-negative bacteria as well as fungus. Their antimicrobial activity and ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml3001215
更新日期:2012-07-12 00:00:00
abstract::Rapid detection and precise evaluation of myocardial viability is necessary to aid in clinical decision making whether to recommend revascularization for patients with myocardial infarction (MI). Three novel 18F-labeled 1-hydroxyanthraquinone derivatives were synthesized, characterized, and evaluated as potential necr...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00398
更新日期:2016-12-28 00:00:00
abstract::The first allosteric, type III inhibitor of LIM-kinase 2 (LIMK2) is reported. A series of molecules that feature both an N-phenylsulfonamide and tertiary amide were not only very potent at LIMK2 but also were extremely selective against a panel of other kinases. Enzymatic kinetic studies showed these molecules to be n...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500242y
更新日期:2014-08-07 00:00:00
abstract::The Hu family of RNA-binding proteins plays a crucial role in post-transcriptional processes; indeed, Hu-RNA complexes are involved in various dysfunctions (i.e., inflammation, neurodegeneration, and cancer) and have been recently proposed as promising therapeutic targets. Intrigued by this concept, our research effor...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.9b00659
更新日期:2020-01-28 00:00:00
abstract::Starting from clinical candidates Firategrast, Valategrast, and AJM-300, a series of novel macrocyclic platelet collagen receptor α2β1 antagonists were developed. The amino acid derived low molecular weight 14-18-membered macrocycles turned out to be highly active toward integrin α2β1 with IC50s in the low nanomolar r...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml4004556
更新日期:2014-01-10 00:00:00
abstract::Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00267
更新日期:2020-10-13 00:00:00
abstract::We report herein the identification of MK-4409, a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. Starting from a high throughput screening (HTS) hit, medicinal chemistry efforts focused on optimizing of FAAH inhibition in vitro potency, improving the pharmacokinetic (PK) profile, and increasing in v...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml5001239
更新日期:2014-04-10 00:00:00
abstract::A series of 12N-substituted sophoridinamine derivatives were synthesized and evaluated for their cytotoxic activities in human HepG2 hepatoma cells. Structure-activity relationship revealed that introduction of a suitable arylidene or arylethyl at the N'-end could greatly enhance antiproliferation potency. Among them,...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00466
更新日期:2017-01-05 00:00:00
abstract::By employing a phenotypic screen, a set of compounds, exemplified by 1, were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of 1 as affinity bait identifie...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00551
更新日期:2020-12-23 00:00:00
abstract::Pursuing our effort for developing effective inhibitors of the cancer-related hCA IX isoform, here we describe the synthesis of novel benzofuran-based carboxylic acid derivatives, featuring the benzoic (9a-f) or hippuric (11a,b) acid moieties linked to 2-methylbenzofuran or 5-bromobenzofuran tails via an ureido linker...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00094
更新日期:2020-03-18 00:00:00
abstract::Water-soluble cyclodextrin (CyD) complexed with porphyrin derivatives with different substituents in the meso-positions showed different photodynamic activities toward cancer cells under illumination at wavelengths over 600 nm, the most suitable wavelengths for photodynamic therapy (PDT). In particular, aniline- and p...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.7b00098
更新日期:2017-04-19 00:00:00
abstract::The N-methyl-d-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, gated by the endogenous coagonists glutamate and glycine, permeable to Ca2+ and Na+. NMDAR dysfunction is associated with numerous neurological and psychiatric disorders, including schizophrenia, depression, and Alzheimer's disease. Recentl...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00388
更新日期:2016-10-31 00:00:00
abstract::Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.6b00236
更新日期:2016-08-24 00:00:00
abstract::This report describes the discovery of RAD140, a potent, orally bioavailable, nonsteroidal selective androgen receptor modulator (SARM). The characterization of RAD140 in several preclinical models of anabolic androgen action is also described. ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml1002508
更新日期:2010-12-02 00:00:00
abstract::The receptor for the neuropeptide relaxin 3, relaxin family peptide 3 (RXFP3) receptor, is an attractive pharmacological target for the control of eating, addictive, and psychiatric behaviors. Several structure-activity relationship studies on both human relaxin 3 (containing 3 disulfide bonds) and its analogue A2 (tw...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.0c00456
更新日期:2020-10-22 00:00:00
abstract::Fatty acid amide hydrolase (FAAH) is an integral membrane serine hydrolase that degrades the fatty acid amide family of signaling lipids, including the endocannabinoid anandamide. Genetic or pharmacological inactivation of FAAH leads to analgesic and anti-inflammatory phenotypes in rodents without showing the undesira...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml100190t
更新日期:2011-02-10 00:00:00
abstract::The identification of Pim-1/2 kinase overexpression in B-cell malignancies suggests that Pim kinase inhibitors will have utility in the treatment of lymphoma, leukemia, and multiple myeloma. Starting from a moderately potent quinoxaline-dihydropyrrolopiperidinone lead, we recognized the potential for macrocyclization ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/acsmedchemlett.5b00403
更新日期:2016-02-12 00:00:00
abstract::An efficient method for the reconstruction of the 9-dihydroerythromycin A macrolactone skeleton has been established. The key steps are oxidative cleavage at the 11,12-position and reconstruction after insertion of an appropriate functionalized amino alcohol. Novel 15-membered macrolides, we named as "11a-azalides", w...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml100252s
更新日期:2010-12-30 00:00:00
abstract::Representative d-amino acid oxidase (DAAO) inhibitors were subjected to in vitro liver microsomal stability tests in the absence or presence of uridine diphosphate glucuronic acid (UDPGA). While carboxylate-based DAAO inhibitors displayed little glucuronidation, most DAAO inhibitors containing α-hydroxycarbonyl moiety...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
doi:10.1021/ml500335z
更新日期:2014-10-21 00:00:00