Pyridine-pyrimidine amides that prevent HGF-induced epithelial scattering by two distinct mechanisms

Siddiqui‐Jain, Adam; Hoj, Jacob P.; Hargiss, John B.; Hoj, Taylor H; Payne, Carter J.; Ritchie, Collin A.; Herron, Steven R.; Quinn, Colette F.; Schuler, Jeffrey T.; Hansen, Marc D.H.

doi:10.1016/j.bmcl.2017.07.063

Cited by 6 publications

(2 citation statements)

References 15 publications

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“…EMT process and HGF/c-MET pathway are foremost molecular mechanisms of antitumor drug resistance, which significantly promotes the antitumor effect of drugs on cancer cells. [67][68][69][70][71][72][73][74][75][76][77] Jiao et al showed that HGF treatment induced gefitinib resistance in human lung cancer cells and miR-1-3 p or miR-206 sensitizes cells to gefitinib by inhibition of c-Met and EMT process. 78 In the present work, we found that ARQ-197 inhibited the EMT process of HCC cells and enhanced the sensitivity of HCC cells to sorafenib.…”

Section: Discussionmentioning

confidence: 99%

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

Gao¹,

Chen²,

Huang³

et al. 2019

OTT

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Background: Hepatocellular carcinoma (HCC) is one of the heaviest malignant burdens in China. Molecular targeting agent, sorafenib, is the main therapeutic option for antitumor therapy of advanced HCC, but it is currently too expensive for the public and its therapeutic effect does not satisfy initial expectation. Therefore, it is important to develop more effective molecular targeted therapeutic strategies for advanced HCC. Materials and methods: The antitumor effects of sorafenib or ARQ-197, an antagonist of c-MET (tyrosine-protein kinase Met or hepatocyte growth factor receptor), were examined by MTT or in murine tumor model. The effect of ARQ-197 on epithelial-mesenchymal transition (EMT) or multidrug resistance (MDR) was examined by quantitative real-time PCR for the expression of related genes. The clearance of sorafenib in HCC cells was detected by liquid chromatography-mass spectrometry/mass spectrometry. Results: ARQ-197 treatment enhanced the sensitivity of HCC cells to sorafenib. Mechanistic studies indicated that ARQ-197 inhibited the expression of EMT-and MDR-related genes. Moreover, ARQ-197 treatment decelerated the clearance of sorafenib in cultured HCC cells and subcutaneous HCC tumors in nude mice. Conclusion: In the present work, our data suggested that ARQ-197 decelerated the clearance of sorafenib in HCC cells and enhanced the antitumor effect of sorafenib.

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Section: Discussionmentioning

confidence: 99%

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

Gao¹,

Chen²,

Huang³

et al. 2019

OTT

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“…Motivated by the success of the quinoxalines synthesis, we decided to apply our methodology for the construction of other scaffolds based on alkynes as convenient building blocks. This approach has been successful for the synthesis of useful acyl-substituted heterocycles (Scheme 5) such as indole, 52 pyrazine, 53 and benzo[b] [1,4]oxazine. 54 To clarify the alkyne oxidation mechanism, a control experiment was carried out (Scheme 6).…”

mentioning

confidence: 99%

Gold(I)-Catalyzed Oxidation of Acyl Acetylenes to Vicinal Tricarbonyls

2019

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Efficient gold(I)-catalyzed oxidation of COR 2 -functionalized internal alkynes to vicinal tricarbonyl compounds by 2,6-dichloropyridine N-oxide proceeds under mild conditions (DCM, rt). This catalytic reaction provides a good to excellent yielding route to diverse tricarbonyls such as α,β-diketoesters, 1,2,3-triketones, and α,β-diketoamides. The utility of these compounds was also demonstrated by facile one-pot synthesis of important azaheterocyclic systems.

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Pharmacology and in vivo efficacy of pyridine-pyrimidine amides that inhibit microtubule polymerization

Siddiqui‐Jain

Hoj

Cescon

et al. 2018

Bioorganic & Medicinal Chemistry Letters

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Pyridine-pyrimidine amides that prevent HGF-induced epithelial scattering by two distinct mechanisms

Cited by 6 publications

References 15 publications

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

<p>ARQ-197 enhances the antitumor effect of sorafenib in hepatocellular carcinoma cells via decelerating its intracellular clearance</p>

Gold(I)-Catalyzed Oxidation of Acyl Acetylenes to Vicinal Tricarbonyls

Pharmacology and in vivo efficacy of pyridine-pyrimidine amides that inhibit microtubule polymerization

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