Abstract：
:The study by Huang et al. is an excellent example of rational structure-based and lipophilic-efficiency optimization of crizotinib (Xalkori) aimed at novel ALK inhibitors capable of overcoming clinically acquired resistance against the current drug in NSCLC patients. One of the most promising new compounds, 8e, displayed subnanomolar potency against ALK(WT) and a panel of the crizotinib-resistant mutants and demonstrated robust in vivo antitumor efficacy. The super suppressing potency of this compound on ROS1 kinase may also indicate its great potential to overcome the resistance associated with the most recently identified ROS1 mutation.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Lu X,Ding Kdoi
10.1021/jm500178rsubject
Has Abstractpub_date
2014-02-27 00:00:00pages
1167-9issue
4eissn
0022-2623issn
1520-4804journal_volume
57pub_type
杂志文章abstract：:Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In genera...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a014
更新日期：1987-01-01 00:00:00
abstract：:Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity fo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040780c
更新日期：2004-09-09 00:00:00
abstract：:The increasing prevalence of diabetes has accelerated the search for new drugs derived from natural sources. To define the functional features of two such families of compounds, the flavonols and the ethyl caffeates, we have determined the high-resolution structures of representative inhibitors in complex with human p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301273u
更新日期：2012-11-26 00:00:00
abstract：:Prolonged drug-target occupancy has become increasingly important in lead optimization, and biophysical assays that measure residence time are in high demand. Here we report a practical label-free assay methodology that provides kinetic and affinity measurements suitable for most target classes without long preincubat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01829
更新日期：2018-06-28 00:00:00
abstract：:We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01342
更新日期：2020-12-10 00:00:00
abstract：:The pharmaceutical industry has recognized that many drug-like molecules can self-aggregate in aqueous media and have physicochemical properties that skew experimental results and decisions. Herein, we introduce the use of a simple NMR strategy for detecting the formation of aggregates using dilution experiments that ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400535b
更新日期：2013-06-27 00:00:00
abstract：:Protein arginine methylation is a posttranslational modification critical for a variety of biological processes. Misregulation of protein arginine methyltransferases (PRMTs) has been linked to many pathological conditions. Most current PRMT inhibitors display limited specificity and selectivity, indiscriminately targe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401884z
更新日期：2014-03-27 00:00:00
abstract：:Certain L1210-active bis(guanylhydrazones) have structural and biological properties in common with the DNA minor groove binding, antileukemic, bisquaternary ammonium heterocycles. Monitoring of the DNA binding of the bis(guanylhydrazones), by fluorimetric quantitation of drug displacement of DNA-bound ethidium, shows...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00196a016
更新日期：1979-10-01 00:00:00
abstract：:Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00375a013
更新日期：1984-09-01 00:00:00
abstract：:We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253-1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020276c
更新日期：2002-12-05 00:00:00
abstract：:The kinome-wide virtual profiling of small molecules with high-dimensional structure-activity data is a challenging task in drug discovery. Here, we present a virtual profiling model against a panel of 391 kinases based on large-scale bioactivity data and the multitask deep neural network algorithm. The obtained model...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00855
更新日期：2020-08-27 00:00:00
abstract：:High-throughput file screening against inhibition of human lung PDE4 led to the discovery of 3-ethyl-1-(4-fluorophenyl)-6-phenyl-7-oxo-4, 5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine (11) as a novel PDE4 inhibitor. Subsequent SAR development, using an eosinophil PDE assay, led to analogues up to 50-fold more potent tha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9800090
更新日期：1998-06-18 00:00:00
abstract：:Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049035q
更新日期：2005-04-07 00:00:00
abstract：:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00368a013
更新日期：1984-02-01 00:00:00
abstract：:Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs lice...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0504048
更新日期：2006-04-20 00:00:00
abstract：:The synthesis and biological activity of a novel cyclic beta-sheet-type antimicrobial dehydropeptide based on gramicidin S (GS) is described. The GS analogue, containing two (Z)-(beta-3-pyridyl)-alpha,beta-dehydroalanine (DeltaZ3Pal) residues at the 4 and 4' positions (2), was synthesized by solution-phase methodologi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061051v
更新日期：2006-12-28 00:00:00
abstract：:The oxazolidinones are a new class of synthetic antibacterials effective against a broad range of pathogenic Gram-positive bacteria, including multi-drug-resistant strains. Linezolid is the first drug from this class to reach the market and has become an important new option for the treatment of serious infections, pa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm058204j
更新日期：2005-07-28 00:00:00
abstract：:In the present investigation, the last two possible modes of generating conformationally semirigid diacylglycerol (DAG) analogues embedded into five-membered ring lactones as templates III and IV are investigated. The first two templates studied in previous investigations corresponded to 2-deoxyribonolactone (template...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960525v
更新日期：1996-12-06 00:00:00
abstract：:A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00095a005
更新日期：1992-08-21 00:00:00
abstract：:A series of dihydrobenzopyrans and tetrahydroquinolines was synthesized and pharmacologically tested for their ability to inhibit P-glycoprotein mediated daunomycin efflux in multidrug resistant CCRF-CEM vcr1000 cells. Several compounds exhibit activities in the range of the reference compounds verapamil and propafeno...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980517+
更新日期：1999-06-03 00:00:00
abstract：:The Free-Wilson equations are derived for the case of symmetrical substitution and are applied, in four modifications, to in vitro inhibitory activity of 77 organic disulfides against Histoplasma capsulatum. Substituent constants are listed to aid in the design of new inhibitory agents against this human pathogen (and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00238a004
更新日期：1975-04-01 00:00:00
abstract：:Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. P-glycoprotein (P-gp), a promiscuous drug efflux pump, has been extensively studied for its association with MDR due to overexpression in cancer cells. Several P-gp inhibitors or modulators have been investigated in clinical trials in hope ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01457
更新日期：2018-06-28 00:00:00
abstract：:(N)-Methanocarba nucleosides containing bicyclo[3.1.0]hexane replacement of the ribose ring previously demonstrated selectivity as A(3) adenosine receptor (AR) agonists (5'-uronamides) or antagonists (5'-truncated). Here, these two series were modified in parallel at the adenine C2 position. N(6)-3-Chlorobenzyl-5'-N-m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900426g
更新日期：2009-12-10 00:00:00
abstract：:Continuing studies on the chemical modification of the previously reported novel tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert-butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially investigated the stability of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00095a013
更新日期：1992-08-21 00:00:00
abstract：:A series of analogues of buspirone was synthesized in which modifications were made in the aryl moiety, alkylene chain length, and cyclic imide portion of the molecule. These compounds were tested in vitro for their binding affinities to rat brain membrane sites labeled by either the dopamine antagonist [3H]spiperone ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00356a014
更新日期：1983-02-01 00:00:00
abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200330s
更新日期：2011-07-28 00:00:00
abstract：:A series of triarylethylene compounds related to 4-hydroxyclomiphene (2) in which the vinyl Cl substituent was replaced by ethyl (5), Br (6), H (7), CN (8), or NO2 (9) substituents were synthesized to facilitate studies of the molecular actions of synthetic nonsteroidal antiestrogens. The relative binding affinities o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00162a014
更新日期：1986-12-01 00:00:00
abstract：:In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401329s
更新日期：2014-03-13 00:00:00
abstract：:Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized. T...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060232u
更新日期：2006-10-19 00:00:00
abstract：:A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha 2- and/or alpha 3- over alpha 1-containing GABA(A) receptor subtypes and high ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0110789
更新日期：2002-04-25 00:00:00
