Peer-reviewed Publications: ? Wang C, Huo X, Wang L, Meng Q, Liu Z, Liu Q, Sun H, Sun P, Peng J, Liu K. Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1. Sci Rep. 2016 Jun 22;6:28403. ? Wang C, Duan X, Sun X, Liu Z, Sun P, Yang X, Sun H, Liu K, Meng Q. Protective effects of glycyrrhizic acid from edible botanical glycyrrhiza glabra against non-alcoholic steatohepatitis in mice. Food Funct. 2016 Sep 14;7(9):3716-23 ? Wang C1, Liu Z, Sun Y, Chen T, Huo X, Meng Q, Liu Q, Sun H, Sun P, Peng J, Ma X, Liu K. A stronger reversal effect of the combination of dasatinib and menadione on P-gp-mediated multidrug resistance in human leukemia K562/Adr cell line. Rsc Advances, 2017, 7: 17227-17235 ? Wang C, Sun Y, Zhu X, Wu B, Wang Q, Zhen Y, Shu X, Liu K, Zhou Y, Ma X.Novel Quinazoline Derivatives Bearing Various 4-Aniline Moieties as Potent EGFR Inhibitors with Enhanced Activity Against NSCLC Cell Lines. Chem Biol Drug Des. 2016 Apr;87(4):635-43. 2 ? Zhang Y, Wang C, Duan Y, Huo X, Meng Q, Liu Z#, Sun H, Ma X, Liu K#. Afatinib Decreases P-Glycoprotein Expression to Promote Adriamycin Toxicity of A549T Cells. Journal of Cellular Biochemistry, 2017, 9999: 1-10 ? Liu Z, Jia Y, Wang C, Meng Q, Huo X, Sun H, Sun P, Yang X, Ma X, Peng J. Organic anion transporters 1 (OAT1) and OAT3 meditated the protective effect of rhein on methotrexate-induced nephrotoxicity. Rsc Advances, 2017, 7 (41) : 25461-25468 ? Qu M1, Liu Z1, Zhao D, Wang C, Zhang J, Tang Z, Liu K, Shu X, Yuan H, Ma X. Design, synthesis and biological evaluation of sulfonamide- substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity. Bioorg Med Chem. 2017, 25(15): 3989-3996 ? Jia 1, Liu Z1, Wang C, Meng Q, Huo X, Liu Q, Sun H, Sun P, Yang X, Ma X, Liu K. P-gp, MRP2 and OAT1/OAT3 Mediate the Drug-Drug Interaction between resveratrol and methotrexate, Toxicol Appl Pharmacol, 2016 Sep 1; 306: 27-35 ? Wang L, Wang C, Jia Y, Liu Z, Shu X, Liu K. Resveratrol Increases Anti-Proliferative Activity of Bestatin through Downregulating P-Glycoprotein Expression via Inhibiting PI3K/Akt/mTOR Pathway in K562/ADR Cells, J Cell Biochem, 2016, 81: 1233-1239 ? Feng Y, Wang C, Liu Q, Meng Q, Huo X, Liu Z, Sun P, Yang X, Sun H, Qin J, Liu K, Bezafibrate-mizoribine interaction: Involvement of organic anion transporters OAT1 and OAT3 in rats, Eur J Pharm Sci, 2016(81): 119-128 ? Jia Y1, Liu Z1, Huo X, Wang C, Meng Q, Liu Q, Sun H, Sun P, Yang X, Shu X, Liu K, Enhancement effect of resveratrol on the intestinal absorption of bestatin by regulating PEPT1, MDR1 and MRP2 in vivo and in vitro, Int J Pharm, 2015, 495(1): 588-598( ? Chen T, Wang C, Liu Q, Meng Q, Sun H, Huo X, Sun P, Peng J, Liu Z, Yang X and Liu K. Dasatinib reverses the multidrug resistance of breast cancer MCF-7 cells to doxorubicin by downregulating P-gp expression via inhibiting the activation of ERK signaling pathway, Cancer Biol Ther, 2015, 16(1): 106-114 ? Meng Q, Chen XL, Wang CY, Liu Q, Sun HJ, Sun PY, Huo XK, Liu ZH, Yao JH, Liu KX, Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involvedin bile acid homeostasis, Toxicol Appl Pharmacol, 2015, 283(3): 178-186 ? Meng Q, Chen X, Wang C, Liu Q, Sun H, Sun P, Huo X, Liu Z, Yao J, Liu K, Protective Effects of Alisol B 23-acetate via Farnesoid X Receptor-mediated Regulation of Transporters and Enzymes in Estrogen-induced Cholestatic Liver Injury in Mice, Pharm Res, 2015, 32(11): 3688-3698

PUBLICATIONS Appeared so far in over numerous high impact factor peer-reviewed International specialized journals and internationally recognized patents as follows: Research Focus: Drug Design and Preclinical Drug Development *Contributed as a First, corresponding author, or both in selected publications as follows: 1. Eissa N, Khan N, Ojha SK, ?a?ewska D, Kie?-Kononowicz K, *Sadek B The histamine H3 receptor antagonist DL77 ameliorates MK801-induced memory deficits in rats. Front Pharmacol 2018; Accepted. 2. Eissa N, Al-Houqani M, Sadeq A, Ojha SK, Sasse A, *Sadek B. Current enlightenment about aetiology and Pharmacological Treatment of Autism Spectrum Disorder. Front Pharmacol 2018; Accepted. 3. Bastaki SM, Abdulrazzaq YM, Shafiullah M, Wi?cek M, Kie?-Kononowicz K, *Sadek B. Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice. Drug Des Devel Ther. 2018. In Press. 4. Adem A, Madjid N, Kahl U, Holst S, Sadek B, Sandin J, Terenius L, Ögren SO. Nociceptin and the NOP receptor in aversive learning in mice. Eur Neuropsychopharmacol. 2017; In Press. 5. Alachkar A, ?a?ewska D, Kie?-Kononowicz K, *Sadek B. The histamine H3 receptor antagonist E159 reverses memory deficits induced by dizocilpine in passive avoidance and novel object recognition paradigm in rats. Front Pharmacol. 2017; 8:709. 6. Schübler M, *Sadek B, Kottke T, Weizel L, Stark H. Synthesis, molecular properties estimations, and dual dopamine D2 and D3 receptor activities of Benzothiazole-based ligands. Front Chem. 2017; 5:64. 7. Ojha S, Balaji V, Sadek B, Rajesh M. Beneficial Effects of Phytochemicals in Diabetic Retinopathy: Experimental and Clinical Evidence. Eur Rev Med Pharmacol Sci. 2017; 21: 2769-2783. 8. *Sadek B, Oz M, Nurulain SM, Jayaprakash P, Latacz G, Kie?-Kononowicz K, Szyma?ska E. Phenylalanine derivatives with modulating effects on human ?1-glycine receptors and anticonvulsant activity in strychnine-induced seizure model in male adult rats. Epilepsy Res. 2017; 138:124-131. 9. Sultan A, Yang KHS, Isaev D, El Nebrisi E, Syed N, Khan N, Howarth CF, Sadek B, Oz M. Thujone inhibits the function of ?7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm. Toxicology 2017; 384:23-32. 10. *Sadek B, Khan N, Darras FH, Pockes S, Decker M. The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats. Physiol Behav. 2016; 165:383-391. 11. Ojha S, Venkataraman B, Kurdi A, Mahgoub E, Sadek B, Rajesh M. Plant Derived Agents for Counteracting Cisplatin Induced Nephrotoxicity. Oxid Med Cell Longev. 2016; 1-27. 12. *Sadek B, Saad A, Latacz G, Kuder K, Olejarz A, Karcz T, Stark H, Kiec´-Kononowicz. K. Nonimidazole-based histamine H3R antagonists with anticonvulsant activity in different seizure models in male adult rats. Drug Des Devel Ther. 2016; 10:3879-3898. 13. *Sadek B, Saad A, Schwed JS, Weizel L, Walter M, Stark H. Anticonvulsant Effects of | P a g e 6 Isomeric Nonimidazole Histamine H3 Receptor Antagonists. Drug Des Devel Ther. 2016; 10:3633-3651. 14. Al-Tabakha MM, Obaid DEE, Fahelelbom KMS, Sadek B. The Impact of Modern Pharmacy Curriculum on the Student Attitude towards Weight Loss Product Advertisements: A Case Study. J Young Pharm 2016;8(4):456-462. 15. *Sadek B, Saad A, Sadeq A, Jalal F, Stark H. Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases. Behav Brain Res 2016; 312:415-430. 16. Ojha S, Kurdi A, Sadek B, Kaleem M, Cai L, Kamal MA, Mohanraj R. Phytochemicals as prototypes for pharmaceutical leads for drug development against diabetic cardiomyopathy. Curr Pharm Des. 2016; 22(20):3058-70. 17. Lozon Y, Sultan A, Lansdell SJ, Prytkova T, Sadek B, Yang KS, Howarth FC, Millar NS, Oz M. Inhibition of human ?7 nicotinic acetylcholine receptors by cyclic monoterpene carveol. Eur J Pharm. 2016; 776:44-51. 18. Khan N, Saad A, Nurulain SM, Darras FH, Decker M, *Sadek B. The dual-acting H3 receptor antagonist and AChE inhibitor UW-MD-71 dose-dependently enhances memory retrieval and reverses dizocilpine-induced memory impairment in rats. Behav Brain Res 2016; 297:155-164. 19. *Sadek B and Stark H. Cherry-Picked Ligands at Histamine Receptor Subtypes. Neuropharmacology 2016; 106:56-73. 20. *Sadek B, Saad A, Subramanian D, Shafiullah M, ?a?ewska D, Kie?-Kononowiczc K. Anticonvulsant and Procognitive Properties of the Non-imidazole Histamine H3 Receptor Antagonist DL77 in Male Adult Rats. Neuropharmacology 2016; 106:46-55. 21. Nurulain SM, Ojha S, Shafiullah M, Khan N, Oz M, *Sadek B. Protective Effects of the Antihistamine Promethazine Against Acute Paraoxon-methyl and Dicrotophos Toxicity in adult rats. Int J Clin Exp Med. 2015; 10:17891-901. 22. Sharma C, Sadek B, Goyal S, Sinha S, Kamal MA, Ojha S. Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development. Evid Based Complement Alternat Med. 2015; 2015:1-26. 23. Bahi A, *Sadek B, Nurulain SM, Wi?cekc M, Kie?-Kononowicz K. The histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice. Physiol Behav. 2015; 151:189-197. 24. Khan N, Dar A, *Sadek B. Investigation of Cyclooxygenase and Signaling Pathways Involved in Human Platelet Aggregation Mediated by Synergistic Interaction of Various Agonists. Drug Des Devel Ther. 2015; 9:3497-3506. 25. Al-Tabakha MM, Arida AI, Fahelelbom KM, Sadek B, Saeed DA, Abu Jarad RA, Jawadi J. Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules. Drug Dev Ind Pharm. 2015; 41:1726-1737. 26. Al-Tabakha MM, Arida AI, Fahelelbom KMS, Sadek B, Abu Jarad RA. Performances of New Generation of Delayed Release Capsules. J Young Pharm. 2015; 7:36-44. 27. *Sadek B, Khanian SS, Ashoor A, Prytkova T, Ghattas MA, Atatreh N, Nurulain SM, Keun-Hang SY, Howarth FC, Oz M. Effects of antihistamines on the function of human ?7-nicotinic acetylcholine receptors. Eur J Pharm. 2015; 746:308-316. | P a g e 7 28. Lipani L, Odadzic D, Weizel L, Schwed JS, *Sadek B, Stark H. Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs. Eur J Med Chem. 2014; 86:578-588. 29. *Sadek B, Schreeb A, Schwed JS, Weizel L, Stark H. Drug-likeness Approach on 2-aminopyrimidines as Histamine H3 Receptor Ligands. Drug Des Devel Ther. 2014; 8:1499-1513. 30. *Sadek B, Schwed JS, Subramanian D, Weizel L, Walter M, Adem A, Stark H. Non-imidazole histamine H3 receptor ligands incorporating antiepileptic moieties. Eur J Med Chem. 2014; 77C:269-279. 31. *Sadek B, Kuder K, Subramanian D, Shafiullah M, Stark H, ?a?ewska D, Adem A, Kie?-Kononowicz K. Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists. Behav Pharmacol. 2014; 25(3):245-252. 32. Bahi A, Schwed JS, Walter M, Stark H, *Sadek B. Anxiolytic- and antidepressant-like activities of the novel and potent non-imidazole histamine H3 receptor antagonist ST-1283. Drug Des Devel Ther. 2014; 8:627-637. 33. Handzlik J, Bojarski AJ, Sata?a G, Kubacka M, Sadek B; Ashoor A, Siwek A, Wi?cek M, Filipek B, Kie?-Kononowicz K. SAR-Studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands belonging to phenylpiperazine derived hydantoins. Eur J Med Chem. 2014; 78C:324-339. 34. *Sadek B, Alisch R, Buschauer A, Elz S. Synthesis and Dual Histamine H1 and H2 Receptor Antagonist Activity of Cyanoguanidine Derivatives. Molecules 2013; 18:14186-14202. 35. *Sadek B, Shehab S, Wi?cek M, Subramanian D, Shafiullah M, Kie?-Kononowicz K, Adem A. Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol. Bioorg Med Chem Lett. 2013; 23(17):4886-91. 36. Bahi A, *Sadek B, Schwed SJ, Walter M, Stark H. Influence of the novel histamine H3 receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice. Psychopharmacology (Berl) 2013; 228(1):85-95. 37. Ashoor A, Nordman JC, Veltri D, Yang KH, Al Kury L, Shuba Y, Mahgoub M, Howarth FC, Sadek B, Shehu A, Kabbani N, Oz M. Menthol Binding and Inhibition of ?7-Nicotinic Acetylcholine Receptors. PLoS One 2013; 8(7): e67674. 38. Mahgoub M, Keun-Hang SY, Ashoor A, Kabbani N, Al Kury L, Sadek B, Howarth, CF, Isaev D, Galadari S, Oz M. Effects of cannabidiol on the function of ?7-nicotinic acetylcholine receptors. Eur J Pharmacol. 2013; 720(1-3):310-9. 39. Limban C, Missir AV, Fahelelbom KMS, Al-Tabakha MM, Caproiu MT, *Sadek B. Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and PGE2 inhibitory properties. Drug Des Devel Ther. 2013; 7:883-892. 40. Ashoor A, Nordman JC, Veltri D, Yang KH, Shuba Y, Al Kury L, Sadek B, Howarth FC, Shehu A, Kabbani N, Oz M. Menthol inhibits 5-HT3 receptor-mediated currents. J Pharmacol Exp Ther. 2013; 347(2):398-409. 41. *Sadek B, Hamruoni AM, Adem A. Anti-inflammatory agents of the carbamoylmethyl ester class: synthesis, characterization, and pharmacological evaluation. J Inflamm Res. 2013; 6:35-43. | P a g e 8 42. *Sadek B, Ashoor A, Al Mansouri A, Lorke DE, Nurulain SM, Petroianu G, Wainwright M, Oz M. N3,N7-diaminophenothiazinium derivatives as antagonists of ?7-nicotinic acetylcholine receptors expressed in Xenopus oocytes. Pharmacol Res. 2012; 66(3):213-218. 43. *Sadek B, Fahelelbom KMS. Synthesis, Characterization, and Antimicrobial Evaluation of Oxadiazole Congeners. Molecules 2011; 16(6):4339-4347. 44. *Sadek B, Al-Tabakha MM, Fahelelbom KM. Antimicrobial prospect of newly synthesized 1,3-thiazole derivatives. Molecules 2011; 16(11):9386-96. 45. *Sadek B, Limban C, Stecoza EC, Elz S. Synthesis and Antimicrobial Evaluation of Dibenzo[b,e]oxepin-11(6H)-one O-Benzoyloxime Derivatives. Sci Pharm. 2011; 79(4):749-761. 46. *Sadek B, Fahelelbom KMS, Morusciag L, Elz S. Synthesis and Calcium Channel Blocking Activity of 1,4-Dihydropyridine Derivatives Containing Ester Substitute and Phenyl Carbamoyl Group. Am J Applied Sci. 2011; 8(4):303-309. 47. *Sadek B. Imidazole-Substituted Drugs and Tendency for Inhibition of Cytochrome P-450 Isoenzymes. Der Pharma Chemica 2011; 3:410-419. 48. *Sadek B, Elz S, Stark H, Schunack W. Unexpected Partial H1-Receptor Agonism of Imidazole-type H3-Receptor Antagonists Lacking a Basic Side Chain. Inflamm Res. 2004; 53(2):109-115. 49. Grassmann S, Sadek B, Ligneau X, Elz S, Pertz H, Ganellin C, Arrang JM, Schwartz JC, Stark H, Schunack W. Progress in the Proxifan Class: Heterocyclic Congeners as Novel Potent and Selective Histamine H3-Receptor Antagonists. Eur J Pharm Sci. 2002; 15(4):367-78. 50. Sasse A, Ligneau X, Sadek B, Elz S, Pertz H, Ganellin C, Arrang JM, Schwartz JC, Schunack W, Stark H. Benzophenone Derivatives and Related Compounds as Potent Histamine H3-Receptor Antagonists and Potential PET/SPECT Ligands. Arch Pharm (Weinheim) 2001; 334(2):45-52. 51. Sasse A, Sadek B, Ligneau X, Elz S, Pertz H, Luger P, Ganellin C, Arrang JM, Schwartz JC, Schunack W, Stark H. New Histamine H3-Receptor Ligands of the Proxifan Series: Imoproxifan and other Selective Antagonists with High Oral in Vivo Potency. J Med Chem. 2000; 43(17):3335-3343. 52. Stark H, Ligneau X, Sadek B, Ganellin C, Arrang JM, Schwartz JC, Schunack W. Analogues and derivatives of ciproxifan, a novel prototype for generating potent histamine H3-Receptor antagonists. Bioorg Med Chem Lett. 2000; 10(20):2379-2382. 53. Stark H, Sadek B, Krause M, Huels A, Ligneau X, Ganellin C, Arrang JM, Schwartz JC, Schunack W. Novel Histamine H3-Receptor Antagonists with Carbonyl-Substituted 4-(3-Phenoxypropyl)-1H-imidazole Structures like Ciproxifan and related Compounds. J Med Chem. 2000; 43(21):3987-3994.

Pharmaceutical Analysis Drug Applied Research Center Tabriz University of Medical Sciences-Iran

Igor Grachev, M.D., Ph.D. is a Neurologist, Psychiatrist, Neuroscientist, Drug Developer, Translational Medicine/POC, Clinical Development, Medical Affairs and Imaging expert with over 20 years of extensive Pharma industry, academic and CRO biomedical research experience who has had roles of increasing responsibility and scope at MGH/Harvard Medical School, SUNY Upstate Medical University, Schering-Plough, Sanofi-Aventis, Merck, BioClinica, Merck Sharp & Dohme Corp, GE Healthcare, and Novartis Consumer Health. All his industry roles have involved the application of imaging, biomarkers and clinical neuroscience to drug development. Dr. Grachev is a member of the Coalition Against Major Diseases (CAMD), QIBA DCE-MRI, FDG- and amyloid-PET steering committees of RSNA, ADNI and ADNI2, Society of Nuclear Medicine, International Society to Advance Alzheimer Research and Treatment and has written and co-authored over 100 clinical research scientific publications including chapters on imaging biomarkers/technologies in three books “Methods in Pain Research (CRC Press),” “Complex Regional Pain Syndrome (IASP Press)” and “Imaging in CNS Drug Development (Springer Science, NY),” and served as a Chair of Industry Scientific Advisory Board for Parkinson’s Progression Markers Initiative, Michael J. Fox Foundation. Research interest: Neurobiology of Neurodegenerative disorders (Parkinson’s disease, Alzheimer’s disease, Multiple Sclerosis), Insomnia (incl. PSG), OCD, Depression, Anxiety, Schizophrenia, ADHD, Migraine, Acute & Chronic Pain, Stroke and other indications. Expert in clinical biomarkers and the following Imaging modalities: PET, SPECT, and MRI (Gd-MRI, vMRI, fMRI, MRS, DCE-MRI).

Dr. Carolle-Laure KPOUMIE has worked as pediatric assistant physician in pediatric’s department of faculty of medicine in Cameroon, as clinical researcher methodology, scientific writing, public health, oncology, internal medicine and continued her career in pharmaceutical industries in France. She participates in many congress with studies made in hospitals on relevant cases in the framework Studies and clinical research. She became head of department, director, head of district where she continued her research, writing of treatment protocols in different departments for common pathologies encountered in her context, managing Epidemic crisis such as cholera, meningitis, avian influenza, yellow fever and organizes campaigns on infectious diseases ,HIV, cardiovascular diseases, family planning, research on severe malaria, malnutrition in Children and participates in studies on neonatal mortality in underdeveloped countries. She work on ADR in hospital following drug administration, pharmacovigilance, vaccinovigilance, biovigilance, materiovigilance in underdeveloped countries, articles, medical information and therapeutic safety, clinical trials, Post-marketing, and other’s studies.