35^th World Pharmacology and Toxicology Forum September 21-22, 2020 Tokyo, Japan

Biography:

Mal Galina Sergeevna throughout the 30 years dealing with the actual problems of cardiology, pharmacology and clinical pharmacology. In 1993 she defended her thesis and was awarded the degree of candidate of medical sciences.  In 2005, defended her doctoral thesis and awarded the degree of doctor.  Since 2005 she has been working as a professor of pharmacology.  She is the author of 500 scientific papers.  Develops issues of pharmacological correction of atherosclerosis of coronary heart disease, arterial hypertension.  Studies pharmacogenetic approaches to the modification of the drug response in cardiac patients. Her approach to optimizing treatment is based on the pharmacokinetic, pharmacodynamic and pharmacogenetic aspects of the treatment of cardiac patients.  That allows to implement personalized medicine in real life. She and her students present their work internationally.

 

Abstract:

Objective: To assess the degree of expression of the drug response in patients with ischemic heart disease depending of polymorphic variants of lipid metabolism gene-regulators.

Methods: Assessment of lipid composition of blood, molecular genetic methods.

Results: Polymorphic variants of lipid metabolism control genes are also associated with the risk of developing ischemic heart disease.  The risk of developing ischemic heart disease increases with the carriers of the genes LPA (rs10455872) A>G, APOC1 (rs445925) G>A, APOE (rs7412) C>T.

Polymorphic variants of gene-regulators of lipid metabolism influenced the hypolipidemic effect of rosuvastatin in patients with ischemic heart disease.  In patients with polymorphic variants of LPA (rs10455872) A>G, there was a weakening of the cholesterin-lowering effect in homozygous G/G and heterozygous G/A compared to homozygous A/A. In carriers of polymorphic variants APOC1 (rs445925) G>A  the greatest drug response of rosuvastatin in homozigous A/A. A similar trend in the formation of drug metabolism of rosuvastatin was observed in carriers of polymorphic variants APOE (rs7412) C>T: the greatest decrease in total cholesterol was registered in homozygous T/T.

Conclusions: The reduction of total cholesterol was more pronounced in patients whose genotype did not have variant allels of these polymorphisms. 

The influence of polymorphic variants of lipid metabolism gene regulators affects the degree of expression of the drug response of statins in patients with ischemic heart disease.

 

Biography:

Abstract:

Background: Psoriasis is an autoimmune inflammatory skin disease that affects 0.5–3% of the world’s population and current treatment options are posed with limitations. The reduced risk of failure in clinical trials for repositioned drug candidates and the time and cost-effectiveness has popularized drug reposition and computational methods in the drug research community.

Results: The current study attempts to reposition approved drugs for the treatment of psoriasis by docking about 2000 approved drug molecules against fifteen selected and validated anti-psoriatic targets. The docking results showed that a good number of the dataset interacted favorably with the targets as most of them had − 11.00 to − 10.00 kcal/mol binding free energies across the targets. The percentage of the dataset with binding affinity higher than the co-crystallized ligands ranged from 34.76% (JAK-3) to 0.73% (Rac-1). It was observed that 12 out of the 0.73% outperformed all the co-crystallized ligands across the 15 studied proteins. All the 12 drugs identified are currently indicated as either antiviral or anticancer drugs and are of purine and pyrimidine nuclei. This is not surprising given that there is similarity in the mechanism of the mentioned diseases.

Conclusion: This study, therefore, suggests that; antiviral and anticancer drugs could have anti-psoriatic effects, and molecules with purine and pyrimidine structural architecture are likely templates to consider in developing antipsoriatic agents.

Biography:

Kanathip Singsai, 33 years old, I am a lecturer at Department of Pharmaceutical care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand. She graduated a Ph.D. in Pharmacology (Neuropharmacology) at the age of 29 years from Department of Pharmacology, Faculty of Medicine, Khon Kaen University. Her research involves neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, and others related.

 

Abstract:

Streblus asper (SA) belonging Moraceae family is well-known as a folk medicinal plant in Asian countries. This study aimed to investigate the effect of SA leaf extract on preventing memory impairment in zebrafish that is induced by scopolamine. This research using male zebrafish, Danio rerio. The zebrafish were divided into 6 groups including, control group, scopolamine (SCO) group, scopolamine plus rivastigmine 1.5 mg/kg (RV+SCO) group, scopolamine plus SA leaf extract at dose 200, 400 and 800 mg/kg (SA200+SCO, S400+SCO, and SA800+SCO) group, respectively. Spatial memory was evaluated by Colour biased appetite conditioning T-maze test while fear memory was measured by Inhibitory avoidance test. In spatial memory test, the results showed that the RV+SCO group had the best time spent in the green arm and the red arm ratio in the T-maze, followed by SA800+SCO, SA400+SCO, SA200+SCO, control, and SCO group, respectively. However, it had no statistically significant. In fear memory test, the result showed that zebrafishes received SA at dose 200, 400, and 800 mg/kg had significantly increased latency time as 21.75 ± 4.59, 23.75 ± 13.01, and 18.20 ± 18.84 min, respectively when compared to the SCO group (9.80 ± 10.45 min). These results suggested that SA leaf extract might prevent memory impairment in zebrafish especially in fear memory. These findings can be a part of the information for further research to develop SA extract to be the health products to prevent memory impairment or Alzheimer’s disease in the future.

 

 

Biography:

Vuong Trieu, Ph.D. is the founder and chairman of Oncotelic and was appointed to the Company’s Board and to serve as Chairman of the Board and CEO of Mateon in connection with the Merger with Oncotelic. He is an expert is drug repositioning with several high profile successes including Abraxane and Cynviloq- both are billion dollar drugs. He is leading Mateon effort to become the next generation pharmaceutical by leveraging AI data analytics to create a high value pipeline. You don’t know what you don’t know- but there is no excuse for not knowing.

Abstract:

Using the PS antisense platform we were able to target TGF-β2 without impacting on the β1 and β3, thus avoided the toxicity related to β1 knockdown. OT-101 lifts the immunosuppression in the tumor allowing the body to recognize the tumor as foreign.  Once that is in place- everything else is easy.  For example- checkpoint inhibitor given to pts that don’t recognize the tumors as foreign would have no benefits. 

The antisense platform has the potential of replacing small molecules and mAbs as it is a single platform with abundance of clinical safety data and requiring minimum testing for backbone toxicity- much the same way mAb was so attractive as a platform. This has allowed for rapid drug development such as Milasen-  developed from lab to patient in less than year. FDA has approved many antisense drugs recently including: Fomivirsinen, Macugen, Mipomersen, Nusinersen/Spinraza, Exondys, Luxturna, Inotersen, and Patisiran.  One especially high profile early failure is Oblimersen (Genesense, Genta). Poor management of Oblimersen tainted the field especially PS DNA backbone primarily because clinical trials proceeded for more than a decade including multiple phase III trials- despite marginal efficacy data due to wrong target, wrong tissue, and wrong indication. The determinants for successful PS antisense development drawing on our Trabedersen development experience are as follow: 1) Appropriate target without compensatory mechanisms. 2) Clear clinical efficacy across multiple indications. 3) Avoidance of the dreaded pCG island. 4) Target tissue should be the underlying tissues and not blood.