Xinghai Chen, Ph.D.

• Ph.D., North Carolina State University, 1998
• M.S., Nanjing University (China), 1994
• B.S., Nanjing University (China), 1985

After earning his doctorate, Chen had 15 years of experience in an oncology-focused pharmaceutical company, BioNumerik Pharmaceuticals. As Group Leader of the Medicinal Chemistry Drug Discovery Team, he successfully advanced two novel drug candidates from concepts to completed phase 3 trials.

His research interests focus on the development of new strategies in organic, bioorganic and medicinal chemistry to solve biochemical problems at the interface of chemistry and biology. Particularly, he is interested in optimization of drugs in development, on the market or those that are shelved because of lack of efficacy, to develop their second generation new drugs, which benefit patients through a potential new therapy or a better therapy sooner.

This research involves understanding the complex biochemistry involved in drug metabolism and developing innovative chemical solutions to reduce or eliminate the biochemical metabolism to inactive metabolites.

Patents

Geng, Z.; Chen, X.; Parker, A.; Peng, W.; “Substituted 1-[2-(2,4-Dimethyl-thiophenyl)-phenyl] piperazine Compound Or Derivative Thereof, And Pharmaceutical Composition And Use Thereof” PCT/CN2014/087662

Chen, Xinghai; Kochat, Harry; Huang, Qiuli. “Total Synthesis of Karenitecin”. US 8,722,886
Chen, Xinghai; Kochat, Harry; “Germanium-containing Camptothecin Analogues”. US Application number: 20140073793

Chen, Xinghai; Kochat, Harry; Huang, Qiuli. “Deuterated analogs of7-(2-TMS ethyl)-20-S-Camptothecin” US 20120282261

Chen, Xinghai; Petluru, Pavankumar N. V.; Huang, Qiuli; Narkunan, Kesavaram; Hausheer, Frederick. “Platinum analogs with Bis-nitrile-containing Ligands.” US 7777060

Narkunan, Kesavaram; Kochat, Harry; Chen, Xinghai. “Process for preparing highly lipophilic camptothecin derivatives”. US 6723849.

Kochat, Harry; Chen, Xinghai; Wu, Ye; Huang, Qiuli; Wang, Jianyan; Gerusz, Vincent. “Process for synthesizing L-methyleneglutamic acid and analogs.” US 6977311

Huang, Jerry; Kochat, Harry; Chen, Xinghai; “Medicinal disulfide salts”. US 7282602

Narkunan, Kesavaram; Chen, Xinghai; Kochat, Harry; Hausheer, Frederick. “C10-Substituted Camptothecin Analogs.” US 7687497

Narkunan, Kesavaram; Chen, Xinghai; Kochat, Harry; Hausheer, Frederick. “Synthesis of C7-substituted camptothecin analogs as antitumor agents”. US 7687496

Hausheer, Frederick H.; Chen, Xinghai; “ Camptothecin analog with a novel, “flipped” lactone-stable, E-ring and methods for making and using same”. US 7687487

Kochat, Harry; Chen, Xinghai; Huang, Qiuli; Peddaiaghari, Seetharamulu; Hausheer, Frederick H. “Novel highly lipophilic camptothecin analogs” PCT Int. Appl. (2000), WO 2000/066127

Kochat, Harry; Chen, Xinghai; Wu, Ye; Huang, Qiuli; Wang, Jianyan; Gerusz, Vincent. “Process for synthesizing L-methyleneglutamic acid and analogs.” PCT Int. Appl. (2004), WO 2004/039314

Huang, Jerry; Kochat, Harry; Chen, Xinghai; “Medicinal disulfide salts”. PCT Int. Appl. (2006), WO 2006/034327.

Chen, Xinghai; Petluru, Pavankumar N. V.; Huang, Qiuli; Narkunan, Kesavaram; Hausheer, Frederick. “Platinum analogs with Bis-nitrile-containing Ligands.” PCT Int. Appl. (2008), WO/2008/100301

Narkunan, Kesavaram; Chen, Xinghai; Kochat, Harry; Hausheer, Frederick. “C10- Substituted Camptothecin Analogs.” PCT Int. Appl. (2009), WO 2009051578

Narkunan, Kesavaram; Chen, Xinghai; Kochat, Harry; Hausheer, Frederick. “C7- Substituted Camptothecin Analogs.” PCT Int. Appl. (2009), WO 2009051580

Yao S.; Petluru, P. N.; Parker, A. R.; Ding D.; Chen, X.; Kochat H.; Hausheer, F. H.;  “An in situ Chromatography Method for Analyzing Camptothecin in Plasma Protein Solution.”   In preparation.

Yao S.; Petluru, P. N.; Parker, A. R.; Ding D.; Chen, X.; Huang, Q.; Kochat H.; Hausheer, F. H.; “Carboxylate Forms of Camptothecins -CPT, SN22 and Karenitecin Bind Specifically to Site II (Diazepam site) of Human Serum Albumin”  EC Chemistry 2015, 2(1): 97-110

Petluru, P. N.; Ayala, P. Y.; Parker, A. R.; Zhao M.; Jair, K. W.; Chen, X.; Kochat H.; Hausheer, F. H.; “Comprehensive Comparative Analysis of the Morphological Changes in a 12-mer DNA Oligonucleotide upon Platination by Cisplatin, Oxaliplatin and BNP3029 (a Substituted Cyano ligand-based Platinum analogue) using Molecular Dynamics Simulation Studies”, J Phys Chem Biophys 2015, 5:1 1000172

Yao S.; Petluru, P. N.; Parker, A. R.; Ding D.; Chen, X.; Huang, Q.; Kochat H.; Hausheer, F. H.; “Stabilization of the Karenitecin® lactone by alpha‑1 acid glycoprotein”, Cancer Chemotherapy and Pharmacology 2015, 75,  719-728

Petluru, P. N.; Ayala, P. Y.; Parker, A. R.; Zhao M.; Jair, K. W.; Chen, X.; Kochat H.; Hausheer, F. H.; “Comprehensive Comparative Study Using Ab Initio Computational Approaches on the Structures of Cisplatin, Oxaliplatin and BNP3029 (A Novel Substituted Cyano Ligand-based Platinum Analogue) and Activation Energy Barriers for the Attack of Nucleophiles on Cisplatin and BNP3029 and their Monoaquated Derivatives”, J Phys Chem Biophys 2014, 4:6 1000163

Hausheer, F. H.; Parker, A. R.; Petluru, P. N.; Jair, K. W.; Chen, S.; Huang, Q.; Chen, X.; Ayala, P. Y.; Shanmugarajah, D.; Kochat, H. “Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of human aminopeptidase” Cancer Chemotherapy and Pharmacology 2011, 67(2), 381-391.

Hausheer, F. H.; Ding D.; Shanmugarajah, D.; Leverett, B. D.; Huang, Q.; Chen, X.; Kochat H.; Ayala, P. Y.; Petluru, P. N.; Parker, A. R. “Accumulation of BNP7787 in Human Renal Proximal Tubule Cells”, Journal of Pharmaceutical Sciences, 2011, 100(9), 3977-3984.

Hausheer, F. H.; Shanmugarajah, D.; Leverett, B. D.; Chen, X.; Huang, Q.; Kochat H.; Petluru, P. N.; Parker, A. R. “Mechanistic study of BNP7787-mediated cisplatin nephroprotection: modulation of gamma-glutamyl transpeptidase.” Cancer Chemotherapy and Pharmacology 2010, 65(5), 941-951.

Shanmugarajah, D.; Ding, D.; Huang, Q.; Chen, X.; Kochat, H.; Petluru, P. N.; Ayala, P. Y.; Parker, A. R.; Hausheer, F. H. “Analysis of BNP7787 thiol-disulfide exchange reactions in phosphate buffer and human plasma using microscale electrochemical high performance liquid chromatography.” Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences 2009, 877(10), 857-866.

Comins, D. L.; Chen, X.; Larry, M., “Enantiopure N-Acyldihydropyridones as Synthetic Intermediates: Asymmetric Synthesis of (-)-Septicine and (-)-Tylophorine”, Journal Organic Chemistry, 1997, 62, 7435.

Comins, D. L.; LaMunyon, D. H.; Chen, X., “Enantiopure N-Acyldihydropyridones as Synthetic Intermediates: Asymmetric Synthesis of Indolizidine Alkaloids (-)-205A, (-)-207A and (-)-235B”, Journal Organic Chemistry. 1997, 62, 8182.

Comins, D. L.; Joseph, S. P.; Hong, H.; Al-awar, R. S.; Forti, C. J.; Zhang, Y.; Chen, X. LaMunyon, D. H.; Guerra-Weltzien, M., “Asymmetric Synthesis and Synthetic Utility of 2,3-dihydro-4-pyridones”, Pure & Applied Chemistry 1997, 69, 477.

Comins, D. L.; Chen, X.; Joseph, S. P., “Synthesis of 2, 4-Disubstituted N-Acyl-5, 6-dihydro-2-pyridones”, Tetrahedron Letters 1996, 37, 9275.

Comins, D. L.; Joseph, S. P.; Chen, X., “Regiospecific Substitution of N-Acyl-2, 3-dihydro-4-pyridones at C-5 via Halogenation and Cross-coupling”, Tetrahedron Letters, 1995, 36, 9141.

Wang, Y., Chen, X., et al, “Effect of Plasma Protein Binding on the in vitro activity of Karenitecin™ (BNP1350) and Other Camptothecins”, American Association for Cancer Research, 97th Annual Meeting, Chicago, 2006

Yao, S., Chen, X., et al, “Pharmacological Mechanisms Behind the Extended Stability of Karenitecin™, A Novel Camptothecin Analogue: Potential Role of -1-Acid Glycoprotein in Chemotherapeutic Efficacy”, American Association For Cancer Research, 96th Annual Meeting, Anaheim, 2005

Ma,H., Chen, X., et al, “Investigation of the uptake of Tavocept into Dorsal Root Ganglia (DRG) cells”, American Association for Cancer Research, 96th Annual Meeting, Anaheim, 2005

Yao, S., Chen, X., et al, “Pharmacological Mechanisms Behind the Extended Stability of Karenitecin™, A Novel Camptothecin Analogue: Potential Role of -1-Acid Glycoprotein in Chemotherapeutic Efficacy”, American Association for Cancer Research, 96th Annual Meeting, Anaheim, 2005

Ding, D., Chen, X., et al, “Further investigation of the mechanism(s) of action of Tavocept and preliminary studies on its protective ability as a free radical scavenger”, American Association for Cancer Research, 95th Annual Meeting, Orlando, 2004

Yao, S., Chen, X., et al, “Molecular Modeling and Simulation Data Applied to the Study of Experimentally Observed Physiologically Relevant Interactions of Karenitecin™, a Novel Highly Lipophilic Camptothecin Analogue”, American Association for Cancer Research, 95th Annual Meeting, Orlando, 2004

Ding, D., Chen, X., et al, “Nucleic acid binding preferences and intracellular distribution of Karenitecin (BNP1350), a novel highly lipophilic camptothecin analogue”, American Association for Cancer Research, 94th Annual Meeting, San Francisco, 2003

Yao, S., Chen, X., et al, “Studies of the protein binding properties of Karenitecin (BNP1350), a novel highly lipophilic camptothecin analogue”, American Association for Cancer Research, 94th Annual Meeting, San Francisco, 2003

Ma,H., Chen, X., et al, “Development of a new pathophysiological and pharmacological model of chemotherapy-induced peripheral neurotoxicity: Preliminary results from histopathological studies on fetal rat dorsal root ganglion cells”, American Association for Cancer Research, 94th Annual Meeting, San Francisco, 2003

Hausheer, F., Chen, X., et al, “Studies on the potential mechanism(s) underlying the neuroprotective and nephroprotective effects of BNP7787”, American Association for Cancer Research, 94th Annual Meeting, San Francisco, 2003

Hausheer, F., Kochat, H., Chen, X., et al, “BNP1350s (Karenitecin) Superior Molecular Characteristics: Enhanced Therapeutic Performance of Novel, Lipophilic, Lactone Stable Camptothecin Analogues”, American Association for Cancer Research, 92th Annual Meeting, New Orleans, 2001

Hausheer, F., Kochat, H., Chen, X., et al, “BNP7787: A Novel Neuroprotective Agent in Taxane and Platinum Regimens Does not Interfere with Chemotherapeutic Effects”, American Association for Cancer Research, 92th Annual Meeting, New Orleans, 2001

Hausheer, F., Kochat, H., Chen, X., et al, “Karenitecin: Further Developments With BNP1350 – A Novel, Highly Lipophilic, Lactone Stable Camptothecin”, American Association for Cancer Research, 91th Annual Meeting, San Francisco, 2000

Hausheer, F., Kochat, H., Chen, X., et al, “BNP7787: A Novel Chemoprotecting Agent for Taxane and Platinum Toxicity”, American Association for Cancer Research, 91th Annual Meeting, San Francisco, 2000

Hausheer, F., Kochat, H., Chen, X., et al, “Karenitecin: New preclinical developments with BNP1350 a novel, potent highly lipophilic camptothecin”, American Association for Cancer Research, 90th Annual Meeting, Philadelphia, PA, April 10-14, 1999

Comins, D. L.; Chen, X.; Joseph, S. P, “Synthesis of 5-Substituted-2, 3- dihydropyridones”, 109th North Carolina Section Conference, American Chemical Society, University of North Carolina, Chapel Hill, North Carolina, April 22, 1995