Search Results - "Howell, Brett"

Comparing the Liver Safety Profiles of 4 Next-Generation CGRP Receptor Antagonists to the Hepatotoxic CGRP Inhibitor Telcagepant Using Quantitative Systems Toxicology Modeling by Woodhead, Jeffrey L, Siler, Scott Q, Howell, Brett A, Watkins, Paul B, Conway, Charles

“…Abstract Calcitonin gene-related peptide (CGRP) signaling inhibitors have shown efficacy in both the acute and preventive treatment of migraine. Telcagepant, a…”
Get full text

Assessing Liver Effects of Cannabidiol and Valproate Alone and in Combination Using Quantitative Systems Toxicology by Lakhani, Vinal V., Generaux, Grant, Howell, Brett A., Longo, Diane M., Watkins, Paul B.

“…In clinical trials of cannabidiol (CBD) for the treatment of seizures in patients with Dravet syndrome, Lennox–Gastaut syndrome, and tuberous sclerosis…”
Get full text

Quantitative Systems Toxicology Modeling Informed Safe Dose Selection of Emvododstat in Acute Myeloid Leukemia Patients by Yang, Kyunghee, Kong, Ronald, Spiegel, Robert, Baird, John D., O'Keefe, Kylie, Howell, Brett A., Watkins, Paul B.

“…Clinical investigation of emvododstat for the treatment of solid tumors was halted after two patients who were heavily treated with other anticancer therapies…”
Get full text

Analyzing the Mechanisms Behind Macrolide Antibiotic-Induced Liver Injury Using Quantitative Systems Toxicology Modeling by Woodhead, Jeffrey L., Yang, Kyunghee, Oldach, David, MacLauchlin, Chris, Fernandes, Prabhavathi, Watkins, Paul B., Siler, Scott Q., Howell, Brett A.

“…Purpose Macrolide antibiotics are commonly prescribed treatments for drug-resistant bacterial infections; however, many macrolides have been shown to cause…”
Get full text

Prediction of the liver safety profile of a first-in-class myeloperoxidase inhibitor using quantitative systems toxicology modeling by Woodhead, Jeffrey L, Gebremichael, Yeshi, Macwan, Joyce, Qureshi, Irfan A, Bertz, Richard, Wirtz, Victoria, Howell, Brett A

“…The novel myeloperoxidase inhibitor verdiperstat was developed as a treatment for neuroinflammatory and neurodegenerative diseases. During development, a…”
Get full text

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors by Woodhead, Jeffrey L, Brock, William J, Roth, Sharin E, Shoaf, Susan E, Brouwer, Kim L R, Church, Rachel, Grammatopoulos, Tom N, Stiles, Linsey, Siler, Scott Q, Howell, Brett A, Mosedale, Merrie, Watkins, Paul B, Shoda, Lisl K M

“…Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic…”
Get full text

Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury by Yang, Kyunghee, Guo, Cen, Woodhead, Jeffrey L, St Claire, 3rd, Robert L, Watkins, Paul B, Siler, Scott Q, Howell, Brett A, Brouwer, Kim L R

“…Sandwich-cultured hepatocytes (SCH) are metabolically competent and have proper localization of basolateral and canalicular transporters with functional bile…”
Get more information

Quantitative Systems Toxicology Analysis of In Vitro Mechanistic Assays Reveals Importance of Bile Acid Accumulation and Mitochondrial Dysfunction in TAK-875-Induced Liver Injury by Longo, Diane M, Woodhead, Jeffrey L, Walker, Paul, Herédi-Szabó, Krisztina, Mogyorósi, Károly, Wolenski, Francis S, Dragan, Yvonne P, Mosedale, Merrie, Siler, Scott Q, Watkins, Paul B, Howell, Brett A

“…Abstract TAK-875 (fasiglifam), a GPR40 agonist in development for the treatment of type 2 diabetes (T2D), was voluntarily terminated in Phase III trials due to…”
Get full text

Variable responses of karst springs to recharge in the Middle Atlas region of Morocco by Howell, Brett A., Fryar, Alan E., Benaabidate, Lahcen, Bouchaou, Lhoussaine, Farhaoui, Mohamed

“…Springs in the Middle Atlas region of Morocco are important public water supplies, but their responses to storm-event and seasonal forcings have received only…”
Get full text

The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury by Woodhead, Jeffrey L., Watkins, Paul B., Howell, Brett A., Siler, Scott Q., Shoda, Lisl K.M.

“…Idiosyncratic drug-induced liver injury (iDILI) is a serious concern in drug development. The rarity and multifactorial nature of iDILI makes it difficult to…”
Get full text

The Combination of a Human Biomimetic Liver Microphysiology System with BIOLOGXsym, a Quantitative Systems Toxicology (QST) Modeling Platform for Macromolecules, Provides Mechanistic Understanding of Tocilizumab- and GGF2-Induced Liver Injury by Beaudoin, James J, Clemens, Lara, Miedel, Mark T, Gough, Albert, Zaidi, Fatima, Ramamoorthy, Priya, Wong, Kari E, Sarangarajan, Rangaprasad, Battista, Christina, Shoda, Lisl K M, Siler, Scott Q, Taylor, D Lansing, Howell, Brett A, Vernetti, Lawrence A, Yang, Kyunghee

“…Biologics address a range of unmet clinical needs, but the occurrence of biologics-induced liver injury remains a major challenge. Development of cimaglermin…”
Get full text

Assessing Effects of BHV-0223 40 mg Zydis Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym by Longo, Diane M, Shoda, Lisl K M, Howell, Brett A, Coric, Vladimir, Berman, Robert M, Qureshi, Irfan A

“…Abstract For patients with amyotrophic lateral sclerosis who take oral riluzole tablets, approximately 50% experience alanine transaminase (ALT) levels above…”
Get full text

Investigating bile acid-mediated cholestatic drug-induced liver injury using a mechanistic model of multidrug resistance protein 3 (MDR3) inhibition by Beaudoin, James J, Yang, Kyunghee, Adiwidjaja, Jeffry, Taneja, Guncha, Watkins, Paul B, Siler, Scott Q, Howell, Brett A, Woodhead, Jeffrey L

“…Inhibition of the canalicular phospholipid floppase multidrug resistance protein 3 (MDR3) has been implicated in cholestatic drug-induced liver injury (DILI),…”
Get full text

Use of a systems model of drug-induced liver injury (DILIsym®) to elucidate the mechanistic differences between acetaminophen and its less-toxic isomer, AMAP, in mice by Howell, Brett A., Siler, Scott Q., Watkins, Paul B.

“…Acetaminophen (APAP) has been used as a probe drug to investigate drug-induced liver injury (DILI). In mice, 3′-hydroxyacetanilide (AMAP), a less-toxic isomer…”
Get full text

Mechanisms of hepatotoxicity associated with the monocyclic β-lactam antibiotic BAL30072 by Paech, Franziska, Messner, Simon, Spickermann, Jochen, Wind, Mathias, Schmitt-Hoffmann, Anne-Hortense, Witschi, Anne Therese, Howell, Brett A., Church, Rachel J., Woodhead, Jeff, Engelhardt, Marc, Krähenbühl, Stephan, Maurer, Martina

“…BAL30072 is a new monocyclic β-lactam antibiotic under development which provides a therapeutic option for the treatment of severe infections caused by…”
Get full text

Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity by Battista, Christina, Yang, Kyunghee, Stahl, Simone H, Mettetal, Jerome T, Watkins, Paul B, Siler, Scott Q, Howell, Brett A

“…Abstract CKA, a chemokine receptor antagonist intended for treating inflammatory conditions, produced dose-dependent hepatotoxicity in rats but advanced into…”
Get full text

Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury by Woodhead, Jeffrey L, Yang, Kyunghee, Siler, Scott Q, Watkins, Paul B, Brouwer, Kim L R, Barton, Hugh A, Howell, Brett A

“…Inhibition of the bile salt export pump (BSEP) has been linked to incidence of drug-induced liver injury (DILI), presumably by the accumulation of toxic bile…”
Get full text

Interaction of Cationic Drugs with Liposomes by Howell, Brett A, Chauhan, Anuj

“…Interactions between cationic drugs and anionic liposomes were studied by measuring binding of drugs and the effect of binding on liposome permeability. The…”
Get full text

Application of the DILIsym® Quantitative Systems Toxicology drug-induced liver injury model to evaluate the carcinogenic hazard potential of acetaminophen by Eichenbaum, Gary, Yang, Kyunghee, Gebremichael, Yeshitila, Howell, Brett A., Murray, F. Jay, Jacobson-Kram, David, Jaeschke, Hartmut, Kuffner, Edwin, Gelotte, Cathy K., Lai, John C.K., Wikoff, Daniele, Atillasoy, Evren

“…In 2019, the California Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen. The…”
Get full text

Linking physiology to toxicity using DILIsym®, a mechanistic mathematical model of drug-induced liver injury by Shoda, Lisl K. M., Woodhead, Jeffrey L., Siler, Scott Q., Watkins, Paul B., Howell, Brett A.

“…ABSTRACT The drug development industry faces multiple challenges in the realization of safe effective drugs. Computational modeling approaches can be used to…”
Get full text