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Michael L Mohler

Michael L Mohler
Veru Inc.

BSc, MS, PharmD, PhD
Manage IP portfolio via interactions/review of patent lawyers and renewal payors, R&D collab's & internal reporting.

About

40
Publications
8,100
Reads
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1,332
Citations
Introduction
Assist applicants in the pharmaceutical space with intellectual property (IP) issues, including patent prosecution, renewal, and IP strategy. Have deep expertise in the androgen space and several of the applicants are pursuing nonsteroidal androgen or novel types of antiandrogens. Also, serve as a consultant to Pearl Cohen assisting several of their clients with their pharmaceutical patent prosecution.
Additional affiliations
November 2020 - present
Veru Inc.
Position
  • Managing Director
June 2004 - May 2019
GTx Inc.
Position
  • Senior Researcher
Education
September 2012 - June 2013
August 1998 - May 2002
August 1998 - May 2005
University of Tennessee Health Science Center
Field of study
  • Pharmaceutical Science (Medicinal Chemistry)

Publications

Publications (40)
Article
A major challenge for new drug discovery in the area of androgen receptor (AR) antagonists lies in predicting the druggable properties that will enable small molecules to retain their potency and stability during further studies in vitro and in vivo. Indole (compound 8) is a first-in-class AR antagonist with very high potency (IC50 = 0.085 μM) but...
Chapter
The androgen receptor (AR) mediates the endocrine functions of endogenous androgens like testosterone and exerts pleiotropic androgenic (male phenotype development, sexual function) and anabolic (growth and maintenance of musculoskeletal system) effects across most tissues. The AR‐axis, i.e. AR and its downstream effects, is extensively targeted to...
Article
Full-text available
Traditional endocrine therapy for prostate cancer (PCa) has been directed at suppression of the androgen receptor (AR) signaling axis since Huggins et al. discovered that diethylstilbestrol (DES; an estrogen) produced chemical castration and PCa tumor regression. Androgen deprivation therapy (ADT) still remains the first-line PCa therapy. Insuffici...
Article
We report herein the design, synthesis, and pharmacological characterization of a library of novel aryl pyrazol-1-yl-propanamides as selective androgen receptor degraders (SARDs) and pan-antagonists that exert broad-scope AR antagonism. Pharmacological evaluation demonstrated that introducing a pyrazole moiety as the B-ring structural element in th...
Article
In our effort to find small molecule treatments of advanced prostate cancers (PCs), the novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with nov...
Article
Full-text available
Receptor tyrosine kinases (RTKs), in response to their growth factor ligands, phosphorylate and activate downstream signals important for physiological development and pathological transformation. Increased expression, activating mutations and rearrangement fusions of RTKs lead to cancer, inflammation, pain, neurodegenerative diseases, and other di...
Article
This review highlights selective androgen receptor modulators (SARMs) as emerging agents in late-stage clinical development for the prevention and treatment of muscle wasting associated with cancer. Muscle wasting, including a loss of skeletal muscle, is a cancer-related symptom that begins early in the progression of cancer and affects a patient's...
Article
We investigated the in vitro metabolism and estrogenic and antiestrogenic activity of toremifene (TOR), tamoxifen (TAM) and their metabolites to better understand the potential effects of cytochrome P-450 2D6 (CYP2D6) status on the activity of these drugs in women with breast cancer. The plasma concentrations of TOR and its N-desmethyl (NDM) and 4-...
Article
Introduction: Androgen receptor (AR) antagonists are predominantly used as chemical castration to treat prostate cancer (i.e., in conjunction with androgen deprivation therapy (ADT)). Unfortunately, castration-resistant prostate cancer (CRPC) typically develops that is refractory to targeted therapy. Insights into CRPC biology have led to the emer...
Article
Full-text available
In a continued effort to improve upon the previously published 4-substituted methoxybenzoyl-aryl-thiazole (SMART) template, we explored chemodiverse "B" rings and "B" to "C" ring linkage. Further, to overcome the poor aqueous solubility of this series of agents, we introduced polar and ionizable hydrophilic groups to obtain water-soluble compounds....
Article
Importance of the field: Nonsteroidal estrogens have been known since the 1930s. However, the relatively recent (1996) discovery of estrogen receptor subtype beta (ERbeta) suggested a possible paradigm shift away from SERM-like selectivity. Selective ERbeta agonism would potentially allow expansion of estrogenic targeting into new indications (dis...
Article
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Article
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Article
Diabetes is a disease that affects over 150 million people worldwide for which there are multiple oral and injectable medications. Because of trends in obesity and sedentary lifestyles, diabetes rates in both developed and developing countries are increasing at an alarming rate. Current medications are not adequately effective in maintaining long-t...
Article
The effects of 1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol (EDL-155) on the growth of glioma was tested in vitro and in vivo. Normal cultured rat astrocytes and C6 rat glioma were used as a differential screen to test the effects of EDL-155. The compound was preferentially cytotoxic for C6 glioma (EC50=1.5 micromol/l) relative t...
Article
Selective androgen receptor modulators (SARMs) are essentially prostate sparing androgens, which provide therapeutic potential in osteoporosis, male hormone replacement, and muscle wasting. Herein we report crystal structures of the androgen receptor (AR) ligand-binding domain (LBD) complexed to a series of potent synthetic nonsteroidal SARMs with...
Article
Full-text available
Androgen receptor (AR) plays a critical role in the function of several organs including primary and accessory sexual organs, skeletal muscle, and bone, making it a desirable therapeutic target. Selective androgen receptor modulators (SARMs) bind to the AR and demonstrate osteo- and myo-anabolic activity; however, unlike testosterone and other anab...
Article
Sex hormone signaling regulates the growth, differentiation and development of many tissues. The intracellular concentrations of sex hormones are regulated by several enzymes, including the 17β-hydroxysteroid dehydrogenases (17β-HSDs) and 3α- hydroxysteroid dehydrogenases (3α-HSDs). Most notably, these enzymes are involved in the oxidation and redu...
Article
The endogenous glucocorticoid (GC), cortisol, is involved in maintaining homeostatic balance in glucose regulation and immune response while allowing stress adaptation. The glucocorticoid receptor (GR) is required to maintain life and is the target of numerous FDA-approved drugs. Synthetic steroidal GCs are useful in a plethora of conditions charac...
Article
The endogenous glucocorticoid, cortisol, elevates blood glucose and suppresses the immune system. Glucocorticoid (GC) levels rapidly increase in response to physiologic and mental stress, thereby allowing stress adaptation. Unfortunately, the GC response can be excessive, especially under stressful conditions for the organism. The resulting hyperco...
Article
A new series of androgen receptor targeted agents (ARTA) was prepared and tested in androgen-dependent and -independent prostate cancer cell lines. These agents were bicalutamide analogs with isothiocyanato substituted B-rings. Also, the linker sulfone of R-bicalutamide was maintained or replaced with several alternative linkages including ether, a...
Article
Cultured rat astrocytes and C6 rat glioma were used as a differential screen for a variety of 1,2,3,4-tetrahydroisoquinoline (THI) derivatives. Compound 1 [1-(biphenyl-4-ylmethyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydrochloride] selectively blocked the growth of C6 glioma leaving normal astrocytes relatively unaffected. The potential for clin...
Article
The synthesis of chiral oxazolidinedione derived bicalutamide analogs has been discussed.
Article
A novel 1,4-N-->O migration of a disubstituted phenyl ring was observed during N-methylation of a bicalutamide derivative, (2S)-2-(tert-butyldimethylsilanyloxy)-N-(4-cyano-3-trifluoromethylphenyl)-3-(4-fluorophenoxy)-2-methylpropionamide, in the presence of CsF-Celite/acetonitrile and desilylation of (2S)-2-(tert-butyldimethylsilanyloxy)-N-(4-cyano...
Article
The androgen receptor (AR) is a nuclear hormone receptor that, upon binding to testosterone, dihydrotestosterone (DHT) and other endogenous androgens, supports the development, growth and maintenance of masculine features through activation of anabolic and androgenic metabolism. The AR has been demonstrated to be a productive therapeutic target. AR...
Article
A new synthetic methodology for preparing radioactive androgen receptor binding compounds in order to determine receptor-ligands interactions has been developed.
Article
A series of optically active nonsteroidal selective androgen receptor modulators with structures analogous to bicalutamide was prepared by replacing the trifluoromethyl group with iodine and the sulfonyl linker by oxygen.
Article
We examined the three-dimensional quantitative structure-activity relationship (QSAR) of a group of endogenous and synthetic compounds for the androgen receptor (AR) using comparative molecular field analysis (CoMFA). The goal of these studies was to identify structural features necessary for high binding affinity and optimization of selective andr...
Article
A variety of amine complexes with 1-boraadamatane were synthesized and subsequently evaluated for an antiproliferative effect on CD81-enriched cell lines to provide evidence for binding and activation of CD81. CD81 is a member of the tetraspanin family of membrane proteins found in all cell lineages in the liver. CD81 signals for antiproliferation...
Article
The conformation of lividomycin A (1) bound to an aminoglycoside antibiotic 3'-phosphotransferase (APH (3')-IIIa), an enzyme that confers bacterial aminoglycoside resistance, was recently characterized via NMR spectroscopy. In contrast to the previously studied 4,5-disubstituted aminoglycosides, the absence of TRNOEs between protons of rings A (sin...

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