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Silky Bedi Shah A. Khan Majed M. AbuKhader Perwez Alam Nasir A. Siddiqui Asif Husain 《Saudi Pharmaceutical Journal》2018,26(6):755-763
The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need. 相似文献
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Afzal Hussain Perwez Alam Nasir Ali Siddiqui Mohamed Fahad Alajmi Md Tabish Rehman Mohd Abul Kalam Adnan Jathlan Al-Rehaily 《Saudi Pharmaceutical Journal》2018,26(7):970-976
Bergenin and menisdaurin are biologically active components which are found in plant Flueggea virosa (Phyllanthaceae). Bergenin has pharmacological actions such as chemopreventive and antihepatotoxic while menisdaurin has an anti-viral activity which needs its evaluation by an analytical method (UPLC-PDA method) that can be applied to the quality control of pharmaceutical preparations. The developed UPLC-PDA method was applied for identification and quantification of standards bergenin and menisdaurin in the methanol extract of F. virosa (FVME). The analysis was carried out using Eclipse C18 (4.6?×?100?mm, 3.5?µm) UPLC column. The optimized chromatographic condition was achieved at 0.16?mL/min flow rate using gradient system with acetonitrile and water as mobile phase. Both biomarkers were measured at λmax 235?nm in PDA detector at ambient temperature. The developed method furnished sharp and intense peaks of menisdaurin and bergenin at Rt?=?2.723 and 3.068?min, respectively along with r2?>?0.99 for both. The recoveries of bergenin and menisdaurin were found in the range of 99.37–101.49% and 98.20–100.08%, respectively. With other validation data, including precision, specificity, accuracy, and robustness, this method demonstrated excellent reliability and sensitivity. The separation parameters i.e. retention, separation, and resolution factors for resolved standards (bergenin and menisdaurin) were >1, which showed good separation. The quantity of bergenin and menisdaurin in the FVME sample was found as 15.16 and 3.28% w/w, respectively. The developed UPLC-PDA method could be conveniently adopted for the routine quality control analysis. 相似文献
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Gastrocutaneous fistula after gastrostomy tube removal may persist for a prolonged period. We present a case of a 58-year-old woman with a GCF that had persisted for 5 months following the removal of an endoscopically-placed gastrostomy tube (PEG). Conservative therapy with anti-acid medications and administering motility agents was unsuccessful. For the closure of the GCF, the endoscopic metal clips were used to close the fistula. 相似文献
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Nadeem Siddiqui Md. Jawaid Akhtar M. Shahar Yar Priya Ahuja Waquar Ahsan Sharique Ahmed 《Medicinal chemistry research》2014,23(11):4915-4925
A series of 3-(4-substitutedphenyl)-N-(5-(4-substitutedphenyl-1,3,4-oxadiazol-2-yl)but-2-enamide were synthesized using pharmacophoric elements for in vivo anticonvulsant activity yielding two potent candidates (4d and 4j) in the Phase I and Phase II screening employing maximal electroshock seizure and subcutaneous pentylenetetrazole test having minimal neurotoxicity. Their Phase II screen depicted an increment of nearly 2–10 times for MES and 7–67 folds for scPTZ in the therapeutic index and protective index—the two mainstays in the drug discovery. 相似文献
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Naveed T. Siddiqui MD Cristian Arzola MD Iram Ahmed MD Sharon Davies MD Jose C. A. Carvalho MD PhD 《Journal canadien d'anesthésie》2014,61(8):710-716