Annual Review of Pharmacology and Toxicology Annual Review of Pharmacology and Toxicology RSS feedThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Hear and Now: Ongoing Clinical Trials to Prevent Drug-Induced Hearing Loss
Annu Rev Pharmacol Toxicol. 2023 Aug 10. doi: 10.1146/annurev-pharmtox-033123-114106. Online ahead of print.ABSTRACTEach year over half a million people experience permanent hearing loss caused by treatment with therapeutic drugs with ototoxic side effects. There is a major unmet clinical need for therapies that protect against this hearing loss without reducing the therapeutic efficacy of these lifesaving drugs. At least 17 clinical trials evaluating 10 therapeutics are currently underway for therapies aimed at preventing aminoglycoside- and/or cisplatin-induced ototoxicity. This review describes the preclinical and clini...
Source: Annual Review of Pharmacology and Toxicology - August 10, 2023 Category: Drugs & Pharmacology Authors: John Lee Katharine Fernandez Lisa L Cunningham Source Type: research

Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders
Annu Rev Pharmacol Toxicol. 2023 Aug 8. doi: 10.1146/annurev-pharmtox-051921-023858. Online ahead of print.ABSTRACTCholinergic regulation of dopamine (DA) signaling has significant implications for numerous disorders, including schizophrenia, substance use disorders, and mood-related disorders. The activity of midbrain DA neurons and DA release patterns in terminal regions are tightly regulated by cholinergic neurons found in both the striatum and the hindbrain. These cholinergic neurons can modulate DA circuitry by activating numerous receptors, including muscarinic acetylcholine receptor (mAChR) subtypes. This review spe...
Source: Annual Review of Pharmacology and Toxicology - August 8, 2023 Category: Drugs & Pharmacology Authors: Eric J Nunes Nii A Addy P Jeffrey Conn Daniel J Foster Source Type: research

Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders
Annu Rev Pharmacol Toxicol. 2023 Aug 8. doi: 10.1146/annurev-pharmtox-051921-023858. Online ahead of print.ABSTRACTCholinergic regulation of dopamine (DA) signaling has significant implications for numerous disorders, including schizophrenia, substance use disorders, and mood-related disorders. The activity of midbrain DA neurons and DA release patterns in terminal regions are tightly regulated by cholinergic neurons found in both the striatum and the hindbrain. These cholinergic neurons can modulate DA circuitry by activating numerous receptors, including muscarinic acetylcholine receptor (mAChR) subtypes. This review spe...
Source: Annual Review of Pharmacology and Toxicology - August 8, 2023 Category: Drugs & Pharmacology Authors: Eric J Nunes Nii A Addy P Jeffrey Conn Daniel J Foster Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance
Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.ABSTRACTHere we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding g...
Source: Annual Review of Pharmacology and Toxicology - July 31, 2023 Category: Drugs & Pharmacology Authors: Ruth Nussinov Hyunbum Jang Source Type: research

High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-112122-104310. Online ahead of print.ABSTRACTTraditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique research consortium of federal public health agencies, was established to address and identify toxicity concern...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Caitlin Lynch Srilatha Sakamuru Masato Ooka Ruili Huang Carleen Klumpp-Thomas Paul Shinn David Gerhold Anna Rossoshek Sam Michael Warren Casey Michael F Santillo Suzanne Fitzpatrick Russell S Thomas Anton Simeonov Menghang Xia Source Type: research

LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-031023-100609. Online ahead of print.ABSTRACTLipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based ther...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Erfan Tasdighi Rishav Adhikari Omar Almaadawy Thorsten M Leucker Michael J Blaha Source Type: research

Pharmacogenomics Beyond Single Common Genetic Variants: The Way Forward
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-051921-091209. Online ahead of print.ABSTRACTInterindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response to drugs with regard to efficacy and safety. Enabled by both technological and conceptual advances, the field of pharmacogenomics is developing rapidly. Major progress in omics profiling methods has enabled novel genotypic and phenotypic characterization of patients and biobanks. These developments are paralleled by advances in machine learni...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Volker M Lauschke Yitian Zhou Magnus Ingelman-Sundberg Source Type: research

High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-112122-104310. Online ahead of print.ABSTRACTTraditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique research consortium of federal public health agencies, was established to address and identify toxicity concern...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Caitlin Lynch Srilatha Sakamuru Masato Ooka Ruili Huang Carleen Klumpp-Thomas Paul Shinn David Gerhold Anna Rossoshek Sam Michael Warren Casey Michael F Santillo Suzanne Fitzpatrick Russell S Thomas Anton Simeonov Menghang Xia Source Type: research

LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-031023-100609. Online ahead of print.ABSTRACTLipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based ther...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Erfan Tasdighi Rishav Adhikari Omar Almaadawy Thorsten M Leucker Michael J Blaha Source Type: research