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The impact of current investigational drugs for acne on future treatment strategies
Expert Opin Investig Drugs. 2024 Feb 19:1-6. doi: 10.1080/13543784.2024.2313091. Online ahead of print.ABSTRACTINTRODUCTION: Acne vulgaris is one of the most prevalent diseases worldwide with a considerably high cost and a burden on quality of life. There are currently many topical and systemic therapies for acne; however, many are limited by their local adverse event profile. This review provides an update on current, novel Phase I and II trials for acne vulgaris.AREAS COVERED: This review searched the National Institutes of Health US National Library of Medicine online database of clinical trials (ClinicalTrials.gov) for...
Source: Expert Opinion on Investigational Drugs - February 19, 2024 Category: Drugs & Pharmacology Authors: Heli A Patel Lily Guo Steven R Feldman Source Type: research

GPR119 agonists for type 2 diabetes: past failures and future hopes for preclinical and early phase candidates
This article reviews studies focused on GPR119 agonism in animal models of T2D and in patients with T2D.EXPERT OPINION: GPR119 agonists in vitro and in vivo can potentially regulate incretin hormone release from the gut, then pancreatic insulin release which regulates blood glucose concentrations. However, the success in controlling glucose homeostasis in rodent models of T2D and obesity, failed to translate to early-stage clinical trials in patients with T2D. However, in more recent studies, acute and chronic dosing with the GPR119 agonist DS-8500a had increased efficacy, although this compound was discontinued for furthe...
Source: Expert Opinion on Investigational Drugs - February 19, 2024 Category: Drugs & Pharmacology Authors: Deanne H Hryciw Rhiannon K Patten Raymond J Rodgers Joseph Proietto Dana S Hutchinson Andrew J McAinch Source Type: research

Correction
Expert Opin Investig Drugs. 2024 Feb 19:1. doi: 10.1080/13543784.2024.2319956. Online ahead of print.NO ABSTRACTPMID:38372200 | DOI:10.1080/13543784.2024.2319956 (Source: Expert Opinion on Investigational Drugs)
Source: Expert Opinion on Investigational Drugs - February 19, 2024 Category: Drugs & Pharmacology Source Type: research

Deterministic reprogramming and signaling activation following targeted therapy in non-small cell lung cancer driven by mutations or oncogenic fusions
Expert Opin Investig Drugs. 2024 Feb 19. doi: 10.1080/13543784.2024.2320710. Online ahead of print.ABSTRACTINTRODUCTION: Targeted therapy is used to treat lung adenocarcinoma caused by epidermal growth factor receptor (EGFR) mutations in the tyrosine kinase domain and rare subtypes (<5%) of non-small cell lung cancer. These subtypes include fusion oncoproteins like anaplastic lymphoma kinase (ALK), ROS1, rearranged during transfection (RET), and other receptor tyrosine kinases (RTKs). The use of diverse selective oral inhibitors, including those targeting rat sarcoma viral oncogene homolog (KRAS) mutations, has signific...
Source: Expert Opinion on Investigational Drugs - February 19, 2024 Category: Drugs & Pharmacology Authors: Rafael Rosell Carlos Pedraz-Valdunciel Anisha Jain Chandan Shivamallu Andr és Aguilar Source Type: research

Drugs of the future for diarrhea-predominant irritable bowel syndrome: an overview of current investigational drugs
Expert Opin Investig Drugs. 2024 Feb 17. doi: 10.1080/13543784.2024.2320703. Online ahead of print.ABSTRACTINTRODUCTION: Irritable bowel syndrome (IBS) has a significant impact on society and quality of life. Current treatments are ineffective, and new investigational drugs are necessary.AREAS COVERED: Numerous potential therapies are developing, targeting different areas such as cannabinoid signaling, opioid receptors, tachykinin (NK2) receptors, β3-adrenergic receptors, intestinal microbiota, inflammation, and 5HT receptors. Clinical trial evidence has shown that loperamide, eluxadoline, alosetron, ramosetron, bile acid...
Source: Expert Opinion on Investigational Drugs - February 17, 2024 Category: Drugs & Pharmacology Authors: Shilan Mozaffari Shekoufeh Nikfar Mohammad Abdollahi Source Type: research

Kallikrein inhibitors for angioedema: the progress of preclinical and early phase studies
Expert Opin Investig Drugs. 2024 Feb 17. doi: 10.1080/13543784.2024.2320700. Online ahead of print.ABSTRACTINTRODUCTION: Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent edema and predominantly caused by the dysregulation of the kinin-kallikrein system.AREAS COVERED: This manuscript presents the results of preclinical and early clinical trials of newer drugs targeting the dysregulated kinin-kallikrein system. ATN-249 is an oral drug that has shown promising results in preclinical and Phase I studies, and good tolerability in the prophylactic treatment of attacks. KVD900 is also an oral agen...
Source: Expert Opinion on Investigational Drugs - February 17, 2024 Category: Drugs & Pharmacology Authors: Henriette Farkas Zsuzsanna Balla Source Type: research

Enhancing anti-CD274 (PD-L1) targeting through combinatorial immunotherapy with bispecific antibodies and fusion proteins: from preclinical to phase II clinical trials
Expert Opin Investig Drugs. 2024 Feb 14. doi: 10.1080/13543784.2024.2319317. Online ahead of print.ABSTRACTINTRODUCTION: Immune checkpoint inhibitors have achieved great success in treatment of many different types of cancer. Programmed cell death protein ligand 1 (PD-L1, CD274) is a major immunosuppressive immune checkpoint and a target for several already approved monoclonal antibodies. Despite this, novel strategies are under development, as the overall response remains low.AREAS COVERED: In this review, an overview of the current biomarkers for response to PD-L1 inhibitor treatment is given, followed by a discussion of...
Source: Expert Opinion on Investigational Drugs - February 14, 2024 Category: Drugs & Pharmacology Authors: Dominik Kiem Matthias Ocker Richard Greil Daniel Neureiter Thomas Melchardt Source Type: research

KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem
Expert Opin Investig Drugs. 2024 Feb 14:1-12. doi: 10.1080/13543784.2024.2318317. Online ahead of print.ABSTRACTINTRODUCTION: Approximately 90% of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in receptor tyrosine-kinases KIT or PDGFRA. Despite the outstanding results of first-line imatinib in advanced GIST, resistance ultimately occurs mainly through secondary mutations in KIT/PDGFRA. Other tyrosine-kinase inhibitors (TKIs) with a broader spectrum of activity against these mutations are approved after imatinib failure. However, response rates and progression-free survival are drastically lower...
Source: Expert Opinion on Investigational Drugs - February 12, 2024 Category: Drugs & Pharmacology Authors: Carlo Mar ía Cicala Iv án Olivares-Rivas Jon Ander Aguirre-Carrillo C ésar Serrano Source Type: research

Investigational pharmacological agents for the treatment of ARDS
Expert Opin Investig Drugs. 2024 Feb 5. doi: 10.1080/13543784.2024.2315128. Online ahead of print.ABSTRACTINTRODUCTION: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous form of lung injury with severe hypoxemia and bilateral infiltrates after an inciting event that results in diffuse lung inflammation with a high mortality rate. While research in COVID related ARDS has resulted in several pharmacotherapeutic agents that have undergone successful investigation, non-COVID ARDS studies have not resulted in many widely accepted pharmacotherapeutic agents despite exhaustive research.AREAS COVERED: The aim of this r...
Source: Expert Opinion on Investigational Drugs - February 5, 2024 Category: Drugs & Pharmacology Authors: Katyayini Aribindi Michelle Lim Satyan Lakshminrusimha Timothy Albertson Source Type: research

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis
Expert Opin Investig Drugs. 2024 Feb 1:1-10. doi: 10.1080/13543784.2024.2311186. Online ahead of print.ABSTRACTINTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU.AREAS COVERED: The index article summarizes t...
Source: Expert Opinion on Investigational Drugs - February 1, 2024 Category: Drugs & Pharmacology Authors: Zheng Xian Thng Jonathan Regenold Albert John Bromeo Amir Akhavanrezayat Ngoc T T Than Anadi Khatri S Saeed Mohammadi Anh N T Tran Yong Un Shin Irmak Karaca Hashem H Ghoraba Christopher Chi Mong Or Quan Dong Nguyen Source Type: research

Experimental autotaxin inhibitors for the treatment of idiopathic pulmonary fibrosis
Expert Opin Investig Drugs. 2024 Feb 1:1-11. doi: 10.1080/13543784.2024.2305126. Online ahead of print.ABSTRACTINTRODUCTION: Idiopathic Pulmonary Fibrosis (IPF) is a progressive, irreversible, and fatal lung disease with unmet medical needs. Autotaxin (ATX) is an extracellular enzyme involved in the generation of lysophosphatidic acid (LPA). Preclinical and clinical data have suggested the ATX-LPAR signaling axis plays an important role in the pathogenesis and the progression of IPF.AREAS COVERED: The aim of this review is to provide an update on the available evidence on autotaxin inhibitors in IPF and further details on ...
Source: Expert Opinion on Investigational Drugs - February 1, 2024 Category: Drugs & Pharmacology Authors: Jacopo Simonetti Marco Ficili Giacomo Sgalla Luca Richeldi Source Type: research