Jean M. Bidlack, Ph.D.

Jean M. Bidlack, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 711
Rochester, NY 14642

Research Bio

Discovery of Samidorphan, a medication currently in multiple Phase 2 and Phase 3 clinical trials:



In collaboration with Dr. Mark P. Wentland at Rensselaer Polytechnic Institute, the main goal of our research is to design, synthesize and characterize oral, long-acting modulators of opioid G protein-coupled receptors (GPCRs) as medications to treat cocaine abuse and other central nervous system disorders in humans. A common structural feature of the large majority of opioids is a phenolic-OH group (see prototypic opioid structure below) that plays a crucial role in molecular recognition via H-bonding to a histidine residue of an opioid GPCR. For many opioids, however, this OH group is responsible for poor oral bioavailability and/or short half-life via O-glucuronidation. In 2001, we published the first report that a carboxamide group (CONH2) was an effective replacement for this prototypic phenolic-OH group of opioids. In addition to high affinity binding to opioid GPCRs, certain carboxamido-substituted opioids have much improved pharmacokinetic properties (relative to their phenolic-OH counterparts) as a consequence of high metabolic stability.

Since 2001, our research group has focused on capitalizing on this discovery to achieve our main goal. Our first-generation opioid modulator in this series was 8-carboxamidocyclazocine (8-CAC) and a next generation agent is samidorphan (formerly referred to as ALKS 33). 8-CAC produced analgesia in mice for 16 hours in comparison to morphine which produces analgesia for less than 2 hours. Our publications describing these discoveries as well as a wealth of structure-activity relationship data are catalogued in the PubMed link found below.

In September 2006, Rensselaer signed a license agreement granting Alkermes Inc. - a biotechnology company now based in Ireland - exclusive rights to a library of opioid compounds discovered by our team. The Bidlack lab continues to work with Alkermes to discover new opioids that may be pharmacotherapeutics. Alkermes recently announced the initiation of multiple phase 3 clinical studies of ALKS 5461 (samidorphan in combination with buprenorphine) for treatment of patients with major depressive disorder. The U.S. Food and Drug Administration (FDA) has granted Fast Track status for ALKS 5461. Alkermes also announced the initiation of multiple phase 2 clinical studies of ALKS 3831, a novel oral atypical antipsychotic drug candidate designed to be a broad spectrum treatment for schizophrenia. ALKS 3831 is composed of samidorphan in combination with the established antipsychotic drug, olanzapine. See the following press releases from Alkermes for details:

Alkermes Announces Initiation of FORWARD-3 and FORWARD-4 Efficacy Studies in Pivotal Program for ALKS 5461 for Treatment of Major Depressive Disorder

Alkermes Announces Initiation of ALKS 5461 Pivotal Clinical Program for Treatment of Major Depressive Disorder

Alkermes Receives Fast Track Designation for ALKS 5461 for Major Depressive Disorder

Alkermes Announces Initiation of Second Phase 2 Clinical Study of ALKS 3831, a Novel Broad-Spectrum Oral Antipsychotic

Alkermes Announces Initiation of Phase 2 Clinical Study of ALKS 3831, Designed to Be a Broad Spectrum Oral Antipsychotic for the Treatment of Schizophrenia

Awards & Honors (National)

College of CSR Reviewers | National Institutes of Health 2010 - Present
Distinguished Service Award | Society on NeuroImmune Pharmacology 2005
Periclean Alumna Scholar Award | Skidmore College 2004
NIH Senior Scientist Award | National Institute of Health 1998 - 2008

Awards & Honors (Local)

Excellence in Research Award | University of Rochester 2007
University Dean's Award for Meritorious Service in Ph.D. Defenses | University of Rochester 2007
The Alumni Award for Excellence in Graduate Education | University of Rochester 2001
Wallace O. Fenn Mentor Award | University of Rochester 1995
Periclean Scholar Award | Skidmore College 1975

Patents

N-Substituted Derivatives of Morphinan and Uses Thereof

United States Serial NO.: 10/222,736
Filed Date: August 15, 2002
Title: N-Substituted Derivatives of Morphinan and Uses Thereof
Invented by: Jean Bidlack, John Neumeyer, Xia-Hui Gu
N-Substituted Derivatives of Morphinan and Uses Thereof

United States Serial NO.: 11/029,247
Filed Date: January 4, 2005
Title: N-Substituted Derivatives of Morphinan and Uses Thereof
Invented by: Jean Bidlack, John Neumeyer, Xia-Hui Gu
Small Molecule Targeting of G-Protein Beta Gamma in Cardiovascular Disease, Including Hypertension, Vascular Injury/Restenosis, and Atherosclerosis

United States Serial NO.: 12/597,509
Filed Date: April 28, 2008
Title: Compositions and Methods for Inhibiting G Protein Signaling
Invented by: Burns Blaxall, Alan Smrcka, Jean Bidlack

Recent Journal Articles

Showing the 5 most recent journal articles. 150 available »

2013 Apr 1
Vanalstine MA, Wentland MP, Alvarez J, Cao Q, Cohen DJ, Knapp BI, Bidlack JM. "Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 9: Synthesis, characterization and molecular modeling of pyridinyl isosteres of N-BPE-8-CAC (1), a high affinity ligand for opioid receptors." Bioorganic & medicinal chemistry letters. 2013 Apr 1; 23(7):2128-33. Epub 2013 Feb 08.
2013 Apr
Hoot MR, Sypek EI, Reilley KJ, Carey AN, Bidlack JM, McLaughlin JP. "Inhibition of G??-subunit signaling potentiates morphine-induced antinociception but not respiratory depression, constipation, locomotion, and reward." Behavioural pharmacology. 2013 Apr; 24(2):144-52.
2012 Apr 26
Neumeyer JL, Zhang B, Zhang T, Sromek AW, Knapp BI, Cohen DJ, Bidlack JM. "Synthesis, binding affinity, and functional in vitro activity of 3-benzylaminomorphinan and 3-benzylaminomorphine ligands at opioid receptors." Journal of medicinal chemistry. 2012 Apr 26; 55(8):3878-90. Epub 2012 Apr 04.
2012 Feb
Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R. "Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins." Future medicinal chemistry. 2012 Feb; 4(2):205-26.
2012 Jan
Dean RL, Eyerman D, Todtenkopf MS, Turncliff RZ, Bidlack JM, Deaver DR. "Effects of oral loperamide on efficacy of naltrexone, baclofen and AM-251 in blocking ethanol self-administration in rats." Pharmacology, biochemistry, and behavior. 2012 Jan; 100(3):530-7. Epub 2011 Oct 25.

Current Appointments

Associate Chair - Department of Pharmacology and Physiology (SMD)
Paul Stark Professorship in Pharmacology - Department of Pharmacology and Physiology (SMD)
Professor - Department of Pharmacology and Physiology (SMD) - Primary

Education

PhD | Biophysics | Univ Rochester Sch Med/Dent1979
MS | Biophysics | Univ Rochester Sch Med/Dent1977
BA | Biology - Chemistry | Skidmore College1975