Hovhannes (Hovik) Gukasyan, PhD has joined the USC School of Pharmacy as associate professor of pharmacology and pharmaceutical sciences (teaching track). In this position, he will play an integral role in developing and growing the school's new undergraduate major in biopharmaceutical sciences.
Gukasyan joins USC after more than 18 years in the pharmaceutical industry. As the senior principal scientist at Pfizer and associate director at AbbVie, he led research and development projects that contributed to the development, characterization and application of drug delivery systems. He also helped advance technologies in novel, early clinical studies.
Most recently, he served as a concurrent adjunct professor at the USC School of Pharmacy and Keck Graduate Institute School of Pharmacy and Health Sciences.
Areas of Expertise (6)
Molecular Drug Delivery
Pfizer Worldwide Research and Development W.E. Upjohn Prizes Award (professional)
2016 Pfizer Worldwide Research and Development W.E. Upjohn Prizes Award for KGI School of Pharmacy 2-week Experiential Training course on site in La Jolla.
USC School of Pharmacy: PhD, Pharmaceutical Sciences 2003
USC: BS, Chemistry 1999
- American Chemical Society
- Association for Research in Vision and Ophthalmology
- American Association of Pharmaceutical Sciences
- Controlled Release of Society
- American Association for Cancer Research
Selected Articles (6)
Design and Characterization of a Pyridone-Containing EZH2 Inhibitor Phosphate ProdrugJournal of Medicinal Chemistry
A pyridone-derived phosphate prodrug of an enhancer of zeste homolog 2 (EZH2) inhibitor was designed and synthesized to improve the inhibitor’s aqueous solubility. This prodrug (compound 5) was profiled in pharmacokinetic experiments to assess its ability to deliver the corresponding parent compound (compound 2) to animals in vivo following oral administration. Results from these studies showed that the prodrug was efficiently converted to its parent compound in vivo. In separate experiments, the prodrug demonstrated impressive in vivo tumor growth inhibition in a diffuse large B-cell lymphoma Karpas-422 cell line-derived xenograft model. The described prodrug strategy is expected to be generally applicable to poorly soluble pyridone-containing EZH2 inhibitors and provides a new option to enable such compounds to achieve sufficiently high exposures in vivo.
Ocular biopharmaceutics: impact of modeling and simulation on topical ophthalmic formulation developmentElsevier Current Trends
2019 The estimation of ocular pharmacokinetics (PK) in various eye tissues is limited because of sampling challenges. Computational modeling and simulation (M&S) tools underpinning the elucidation of drug access routes and prediction of ocular exposure are essential for the mechanistic assessment of biopharmaceutics in the eye. Therefore, theoretical and experimental evaluation of ocular absorption and transit models is necessary. Biopharmaceutical parameter sensitivity analysis based on permeability and drug dose illustrates utility in ocular drug delivery assessment, which could have innovative and cost-saving impacts on ophthalmic product development and therapeutic bioequivalence (BE) evaluations.
Safety Assessment of Formulation Vehicles Following Intravitreal Administration in RabbitsOphthalmic Drug Discovery and Development
Evaluate 21 formulation vehicles administered to rabbits after intravitreal injection for tolerability and safety. Forty-two Dutch Belted rabbits were anesthetized, and the eyes received a single intravitreal injection of the excipient formulation. Clinical signs and ocular irritation responses were recorded twice daily for 7 days and microscopic evaluation of the eyes, optic nerve, and eyelids was completed at 1-week post treatment.
Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design StrategiesJournal fo Medicinal Chemistry
2018 A new series of lactam-derived EZH2 inhibitors was designed via ligand-based and physicochemical-property-based strategies to address metabolic stability and thermodynamic solubility issues associated with previous lead compound 1. The new inhibitors incorporated an sp3 hybridized carbon atom at the 7-position of the lactam moiety present in lead compound 1 as a replacement for a dimethylisoxazole group.
Design and Synthesis of Pyridone-Containing 3,4-Dihydroisoquinoline-1(2H)-ones as a Novel Class of Enhancer of Zeste Homolog 2 (EZH2) InhibitorsJournal of Medicinal Chemistry
A new enhancer of zeste homolog 2 (EZH2) inhibitor series comprising a substituted phenyl ring joined to a dimethylpyridone moiety via an amide linkage has been designed. A preferential amide torsion that improved the binding properties of the compounds was identified for this series via computational analysis. Cyclization of the amide linker resulted in a six-membered lactam analogue, compound 18. This transformation significantly improved the ligand efficiency/potency of the cyclized compound relative to its acyclic analogue. Additional optimization of the lactam-containing EZH2 inhibitors focused on lipophilic efficiency (LipE) improvement, which provided compound 31. Compound 31 displayed improved LipE and on-target potency in both biochemical and cellular readouts relative to compound 18. Inhibitor 31 also displayed robust in vivo antitumor growth activity and dose-dependent de-repression of EZH2 target genes.
PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical ModelsCancer Cell
We report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF-06463922 displayed superior potency against all known clinically acquired ALK mutations, including the highly resistant G1202R mutant. Furthermore, PF-06463922 treatment led to regression of EML4-ALK-driven brain metastases, leading to prolonged mouse survival, in a superior manner. Finally, PF-06463922 demonstrated high selectivity and safety margins in a variety of preclinical studies. These results suggest that PF-06463922 will be highly effective for the treatment of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors because of secondary ALK kinase domain mutations and/or brain metastases.