Lisa M. Broad
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View article: Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine
Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine Open
Aim LY3451838 is a monoclonal antibody against pituitary adenylate cyclase-activating peptide (PACAP), a target in migraine research. The present study aimed to evaluate LY3451838 as a preventive treatment for participants with treatment-r…
View article: Preclinical and clinical evaluation of a novel TRPA1 antagonist LY3526318
Preclinical and clinical evaluation of a novel TRPA1 antagonist LY3526318 Open
The transient receptor potential cation channel member A1 (TRPA1) is heavily implicated in nociceptive signaling in both physiological and pathological pain states. However, it has been challenging to develop TRPA1 antagonists with appropr…
View article: Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states
Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states Open
Transient receptor potential ankyrin 1 (TRPA1) is implicated in physiological and pathological nociceptive signaling, but the clinical benefit of TRPA1 antagonists in chronic pain is not clearly demonstrated. LY3526318 is an oral, potent, …
View article: The atypical ‘hippocampal’ glutamate receptor coupled to phospholipase D that controls stretch‐sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2
The atypical ‘hippocampal’ glutamate receptor coupled to phospholipase D that controls stretch‐sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2 Open
A metabotropic glutamate receptor coupled to phospholipase D (PLD‐mGluR) was discovered in the hippocampus over three decades ago. Its pharmacology and direct linkage to PLD activation are well established and indicate it is a highly atypi…
View article: TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde‐Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology
TRPA1 Antagonist LY3526318 Inhibits the Cinnamaldehyde‐Evoked Dermal Blood Flow Increase: Translational Proof of Pharmacology Open
Transient receptor potential Ankyrin 1 (TRPA1) is an ion channel expressed by sensory neurons, where it mediates pain signaling. Consequently, it has emerged as a promising target for novel analgesics, yet, to date, no TRPA1 antagonists ha…
View article: From structure to clinic: Design of a muscarinic M1 receptor agonist with the potential to treat Alzheimer’s disease
From structure to clinic: Design of a muscarinic M1 receptor agonist with the potential to treat Alzheimer’s disease Open
View article: Acknowledgments
Acknowledgments Open
research assistants from semester to semester
View article: From Structure to Clinic: Discovery of A M1 Muscarinic Acetylcholine Receptor Agonist for the Treatment of Memory Loss in Alzheimer's Disease
From Structure to Clinic: Discovery of A M1 Muscarinic Acetylcholine Receptor Agonist for the Treatment of Memory Loss in Alzheimer's Disease Open
View article: Identification and pharmacological profile of SPP1, a potent, functionally selective and brain penetrant agonist at muscarinic M <sub>1</sub> receptors
Identification and pharmacological profile of SPP1, a potent, functionally selective and brain penetrant agonist at muscarinic M <sub>1</sub> receptors Open
Background and Purpose We aimed to identify and develop novel, selective muscarinic M 1 receptor agonists as potential therapeutic agents for the symptomatic treatment of Alzheimer's disease. Experimental Approach We developed and utilized…
View article: Bitopic Binding Mode of an M1 Muscarinic Acetylcholine Receptor Agonist Associated with Adverse Clinical Trial Outcomes
Bitopic Binding Mode of an M1 Muscarinic Acetylcholine Receptor Agonist Associated with Adverse Clinical Trial Outcomes Open
View article: In Vitro Pharmacological Characterization and In Vivo Validation of LSN3172176 a Novel M1 Selective Muscarinic Receptor Agonist Tracer Molecule for Positron Emission Tomography
In Vitro Pharmacological Characterization and In Vivo Validation of LSN3172176 a Novel M1 Selective Muscarinic Receptor Agonist Tracer Molecule for Positron Emission Tomography Open
View article: Synthesis and Pharmacological Characterization of C4<sub>β</sub>-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1<i>S,</i>2<i>S,</i>4<i>S,</i>5<i>R,</i>6<i>S</i>)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu<sub>3</sub>Receptor Agonist
Synthesis and Pharmacological Characterization of C4<sub>β</sub>-Amide-Substituted 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1<i>S,</i>2<i>S,</i>4<i>S,</i>5<i>R,</i>6<i>S</i>)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY2794193), a Highly Potent and Selective mGlu<sub>3</sub>Receptor Agonist Open
Multiple therapeutic opportunities have been suggested for compounds capable of selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small molecule tools are lacking. As part of our ongoing efforts to identify…
View article: [P3–081]: ESTABLISHING MICROFLUIDIC DEVICES AS AN <i>IN VITRO</i> NEURONAL MODEL FOR STUDYING MOLECULAR AND FUNCTIONAL ASPECTS OF TRANSNEURONAL TAU PROPAGATION
[P3–081]: ESTABLISHING MICROFLUIDIC DEVICES AS AN <i>IN VITRO</i> NEURONAL MODEL FOR STUDYING MOLECULAR AND FUNCTIONAL ASPECTS OF TRANSNEURONAL TAU PROPAGATION Open
A hallmark of neurodegenerative diseases, such as Alzheimer's disease and frontotemporal dementia, is aggregation and accumulation of tau protein as intracellular neurofibrillary tangles. Recent scientific evidence suggests the propagation…
View article: Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors
Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors Open
Modulation of gamma oscillations is important for the processing of information and the disruption of gamma oscillations is a prominent feature of schizophrenia and Alzheimer's disease. Gamma oscillations are generated by the interaction o…
View article: M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss
M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss Open
The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An altern…
View article: TRPV3 in Drug Development
TRPV3 in Drug Development Open
Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP (Transient Receptor Potential) super-family. It is a relatively underexplored member of the thermo-TRP sub-family (Figure 1), however, genetic mutations and use of gen…
View article: An Antibody Biosensor Establishes the Activation of the M1 Muscarinic Acetylcholine Receptor during Learning and Memory
An Antibody Biosensor Establishes the Activation of the M1 Muscarinic Acetylcholine Receptor during Learning and Memory Open
Establishing the in vivo activation status of G protein-coupled receptors would not only indicate physiological roles of G protein-coupled receptors but would also aid drug discovery by establishing drug/receptor engagement. Here, we devel…
View article: Activation of transient receptor potential ankyrin 1 induces<scp>CGRP</scp>release from spinal cord synaptosomes
Activation of transient receptor potential ankyrin 1 induces<span>CGRP</span>release from spinal cord synaptosomes Open
Transient receptor potential ankyrin 1 ( TRPA 1) is a sensor of nociceptive stimuli, expressed predominantly in a subpopulation of peptidergic sensory neurons which co‐express the noxious heat‐sensor transient receptor potential vanilloid …
View article: Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus
Activation of Muscarinic M1 Acetylcholine Receptors Induces Long-Term Potentiation in the Hippocampus Open
Muscarinic M1 acetylcholine receptors (M1Rs) are highly expressed in the hippocampus, and their inhibition or ablation disrupts the encoding of spatial memory. It has been hypothesized that the principal mechanism by which M1Rs influence s…
View article: <sup>123</sup>I-Iododexetimide Preferentially Binds to the Muscarinic Receptor Subtype M<sub>1</sub>In Vivo
<sup>123</sup>I-Iododexetimide Preferentially Binds to the Muscarinic Receptor Subtype M<sub>1</sub>In Vivo Open
The current results suggest that (123)I-iododexetimide preferentially binds to M1R in vivo and can be displaced by M1R ligands. (123)I-iododexetimide may therefore be a useful imaging tool as a way to further evaluate M1R changes in neurop…