Pharmacy, the continuously expanding field of science

Originating from the traditional herbal formulations, nowadays, Pharmacy covers all the disciplines focusing on the behavior of complex pharmaceutical forms, drug-releasing systems, and active compounds in the human body. Masters of pharmaceutical sciences must know the basics of pharmaceutical chemistry, pharmaceutical technology, biotechnology, biology, physiology, pharmacology, and toxicology.

Efficacy and mechanism of KRAS G12C PROTAC in inhibiting the proliferation of pancreatic cancer cells

Pancreatic cancer is a rare but highly malignant cancer with few effective treatments available. Targeting cancers bearing specific genetic mutations offers a new approach for cancer therapy. PROTAC (proteolysis-targeting chimeras) is an emerging technique to design targeted therapy and increasing evidence supports its utility. This study examined the in vitro pharmacodynamics and mechanism of PROTAC K-Ras Degrader-1 (PKD-1), a PROTAC molecule, in inhibiting the proliferation of pancreatic cancer cells. We used a pancreatic cancer cell line, MIA PaCa-2 cells, to examined the binding and degradation-promoting capabilities of PKD-1 on KRAS G12C protein and further evaluated the effects of PKD-1 on cell viability, cell cycle and apoptosis. PKD-1 was able to bind to KRAS G12C protein, promoted its degradation for up to 72 h, reduced cell viability, increased cell cycle arrest and promoted cell apoptosis. Mechanistic study found that the efficacy of PKD-1 was at least partially mediated by promoting 26S proteasome degradation process. Combined, these results extended previous findings and support the potential utility of PROTAC molecules such as PKD-1 as a new treatment strategy against pancreatic cancer.

Pharmacokinetics study of potential anti-CML drug Cyclobentinib (CB1107) by HPLC–MS/MS

Purpose: A simple, sensitive and specific HPLC–MS/MS method was established to analysis the pharmacokinetics of CB1107 in mouses. Methods: A simple, selective, and sensitive high-throughput liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been developed and validated for quantitative determination of CB1107 in rat serum.Chromatographic separation was achieved on a Zorbax Extend C18 Rapid Resolution HD column (4.6 mm × 50 mm, 1.8 μm). The column temperature was maintained at 35℃ and at flow rate of 0.6 mL/min. Injection volume was 20 μL. The mobile phases consisted of 0.1% formic acid in water (mobile phase A)and 0.1% formic acid in acetonitrile (mobile phase B), and total run time was 30min. MS-MS detection was performed in the selected monitoring mode of electrospray positive ionization reaction. Results: The pharmacokinetic characteristics of CB1107 in mice belong to the two-compartment model.When the doses were 400 mg/kg, 600 mg/kg and 800 mg/kg, corresponding area under the plasma concentration-time curve (AUC) respectively were 20.011±1.24 mg/h/L, 26.778±2.19 mg/h/L, 38.82±1.44 mg/h/L, suggesting that CB1107 have a good absorption in the body.And the AUC of three doses are proportional, indicating that CB1107 conforms to linear pharmacokinetics in vivo. Conclusion: This method was successfully applied to study the pharmacokinetics at three different doses of CB1107 after oral administration in mouses. In this study, the bioactivity mechanism of CB1107, by the pharmacokinetic investigation of CB1107 in vivo.

Differentiation between drug-type, fibre-type and intermediate-type in cannabis samples: HPLC-UV versus GC-FID

Cannabis sativa is known to be the most abused illegal drug worldwide. To date it is not only used as a medicine but has been established as a lifestyle product. The most relevant phytocannabinoids represent the ingredients delta-9-tetrahydrocannabinol (9-THC) and cannabidiol (CBD), whereby only 9-THC shows a psychoactive effect. Since 2017, the so-called CBD-hemp containing CBD as main ingredient is distributed in many countries as a legal alternative. In these products, 9-THC must not exceed a certain percentage. It is hardly possible to differentiate between THC-hemp and CBD-hemp presenting a major challenge for authorities. Therefore, there is the need to develop fast and efficient analysis methods to distinguish between fibre-type, drug-type and intermediate-type cannabis products. The aim of this study was to compare two simple and inexpensive HPLC-UV and GC-FID methods for their ability to quantify phytocannabinoids in dried cannabis plant material. For this purpose, a set of 37 fresh and dried cannabis samples randomly chosen from seizures of Austrian police was subject to complementary quantification of 9-THC and CBD. After having taken into account decomposition of certain phytocannabinoids, the result of this quantitative study showed good correlation between HPLC-UV and GC-FID regardless of quantifying cannabis leaves or buds.

Cholinergic receptor blockers affect the protective effect of Angong Niuhuang pill on neurologic deficits and intestinal injury in intracerebral hemorrhage mice

Stroke is a devastating disease, intracerebral hemorrhage (ICH) is a devastating subtype. This study aimed to investigate whether cholinergic receptors participate in the process of Angong Niuhuang Pill (ANP) improving neurological function and relieving intestinal injury in ICH mice. The mice were treated with ANP, cholinergic receptor blockers, atropine (ATR), penehyclidine hydrochloride (PHC) or methyllycaconitine (MLA). Male CD-1 mice were randomly divided into 9 groups, Sham, ICH, ANP (0.2 g/kg), ANP plus ATR, ANP plus PHC, ANP plus MLA, ATR, PHC, MLA. ICH model is made by collagenase VII injection (0.075 U). ANP (0.2 g/kg) was administered by gavage after 30 min of ICH. MLA, ATR, PHC was given at 15 min after ICH. Neurological function was evaluated by Garcia test. Intestinal injury was observed by histological analysis. Endotoxin (ET) was measured by enzyme-linked immunosorbent assay. Compared to the Sham group, the score of Garcia test in the ICH significantly decreased. ANP increased significantly the score of ICH mice. ANP also ameliorated the intestinal injury caused by ICH. Cholinergic receptor blockers reversed partially the improvement of neurological function and intestinal injury by ANP. ANP attenuates the neurological deficits and intestinal injury in ICH mice and the protective effect of ANP may be involved in the regulation of the cholinergic system.

Phylogenetic analyses and genomic variation of the 2019-nCoV

There is a rising global concern about the SARS CoV-2 as a public health threat. Complete genome sequence have been released by the worldwide scientific community for understanding the molecular characteristics and evolutionary origin of this virus. Aim of the current context is to present phylogenetic relationship and genomic variation of 2019-nCoV. Based on availability of genomic information, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Middle East respiratory syndrome, severe acute respiratory syndrome and Bat coronavirus. The phylogenetic tree analysis suggested that SARS CoV-2 significantly clustered with bat SARS like coronavirus genome, however structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. However our phylogenetic and genomic analysis suggests that bats can be the reservoir for this virus. Lack of forest might be the fact in association of bats with human environment. It is also difficult to study on bats due to absence of proper reagent and availability of few species for research. We confirm high sequence similarity (>99%) among sequenced SARS CoV-2 genomes, and 96% genome identity with the bat coronavirus, confirming the notion of a zoonotic origin of SARS CoV-2.