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Find video protocols related to scientific articles indexed in Pubmed.
A Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles.
J. Med. Chem.
PUBLISHED: 11-20-2014
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Gatekeeper T790M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming resistance. Nevertheless, concerns about the risk of non-specific covalent modification have motivated the development of novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation of these olefins into the quinazoline templates produced potent EGFR inhibitors with improved safety and pharmacokinetic properties. A lead compound 5a was validated against EGFRWT, EGFR T790M as well as A431 and H1975 cancer cell lines. Additionally, compound 5a displayed a weaker inhibition against the EGFR-independent cancer cell line SW620 when compared withafatinib. Oral administration of 5a at a dose of 30mg/kg induced tumor regression in a murine-EGFRL858R/T790M driven H1975 xenograft model. Also, 5a exhibited improved oral bioavailability and safety, as well as favorable tissue distribution properties and enhanced brain uptake. These findings provide the basis of a promising strategy toward the treatment of NSCLC patients with drug resistance.
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One-Pot Three-Component Approach to the Synthesis of Polyfunctional Pyrazoles.
Org. Lett.
PUBLISHED: 11-20-2013
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A simple, multicomponent, and straightforward reaction of vinyl azide, aldehyde, and tosylhydrazine affords the construction of 3,4,5-trisubstituted 1H-pyrazoles regioselectively in the presence of base with moderate to excellent yields. A range of functionality could be tolerated in this methodology, and a possible mechanism is proposed.
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Palladium-catalyzed C-H functionalization using guanidine as a directing group: ortho arylation and olefination of arylguanidines.
Org. Lett.
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Palladium-catalyzed C-H functionalization using guanidine as the directing group was achieved under mild reaction conditions. Various guanidine derivatives were produced in moderate to good yields by using simple unactivated arenes or ethyl acrylate as the source of arylation or olefination, respectively.
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Hepatic differentiation of rat mesenchymal stem cells by a small molecule.
ChemMedChem
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Mesenchymal stem cells (MSCs) are capable of self-renewal and multilineage differentiation. A periodic acid-Schiff (PAS) stain-based assay was developed to screen for small-molecule inducers of hepatic differentiation of bone marrow MSCs. 2-(4-Bromophenyl)-N-(4-fluorophenyl)-3-propyl-3H-imidazo[4,5-b]pyridin-5-amine (SJA710-6) was identified as a novel small molecule able to induce the differentiation of rat MSCs (rMSCs) toward hepatocyte-like cells in vitro, where rMSCs treated with SJA710-6 have typical morphological and functional characteristics of hepatic cells, including glycogen storage, urea secretion, uptake of low density lipoprotein (LDL) and expression of hepatocyte-specific genes and proteins. Expression of FoxH1 (FAST1/2) induces the differentiation of rMSCs towards hepatocyte-like cells, suggesting that this gene plays an important role in the hepatic fate specification of rMSCs.
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A "one-pot" multicomponent approach to polysubstituted 4-aminopyridines.
Chem. Commun. (Camb.)
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A novel and facile domino reaction has been developed to synthesize a variety of polysubstituted 4-aminopyridines from ?-azidovinylketones, aldehydes and methylamine derivatives in reasonably good yields under mild conditions. Additionally, a possible mechanism is proposed.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.