Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis.

Abstract:

INTRODUCTION:Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that can lead to permanent disability and deformity. Despite current treatment modalities, many patients are still unable to reach remission. Interleukin-1 receptor-associated kinase 4 (IRAK-4) inhibitors are novel agents designed to suppress immune signaling pathways involved in inflammation and joint destruction in RA. Four IRAK-4 inhibitors have entered clinical trials. AREAS COVERED:This review summarizes the current stage of development of IRAK-4 inhibitors in clinical trials, detailing their chemistry, pharmacokinetics, and therapeutic potential in the treatment of RA. PubMed, Embase and restricted Google searches were conducted using the term 'IRAK-4', and publicly accessible clinical trial databases were reviewed. EXPERT OPINION:IRAK-4 inhibitors are an exciting therapeutic option in RA management because unlike other targeted disease-modifying agents, they target the innate immune system. The role of IRAK-4 as a key component of Toll/Interleukin-1 receptor signaling and its potential for a low rate of infectious complications is particularly exciting and this may facilitate their use in combination treatment. A key aspect of upcoming clinical trials will be the identification of biomarkers predictive of treatment efficacy, which will help to define if and how they will be used in the clinic.

authors

Wiese MD,Manning-Bennett AT,Abuhelwa AY

doi

10.1080/13543784.2020.1752660

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

475-482

issue

5

eissn

1354-3784

issn

1744-7658

journal_volume

29

pub_type

杂志文章,评审
  • Dawn of Aurora kinase inhibitors as anticancer drugs.

    abstract::With the current standard chemotherapy regimens only approximately 25% of acute myelogenous leukaemia (AML) patients survive > 5 years. Aurora kinases are overexpressed in many human cancers. VX-680 inhibited Aurora-A, -B, -C and the FMS-like tyrosine kinase-3 with apparent inhibitory constants of 0.6, 18, 4.6 and 30 ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.13.9.1199

    authors: Doggrell SA

    更新日期:2004-09-01 00:00:00

  • Novel therapies for the prevention of malaria.

    abstract:BACKGROUND:Malaria continues to exact a huge toll on the health of residents of endemic countries. Thus, new approaches to prevention and treatment are needed. OBJECTIVE:To provide an update on novel therapies for the prevention of malaria. METHODS:Systematic MEDLINE search from 1956 to 2008 using the search term 'ma...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780802514039

    authors: Bojang KA

    更新日期:2008-12-01 00:00:00

  • Investigational therapies targeting the androgen signaling axis and the androgen receptor and in prostate cancer - recent developments and future directions.

    abstract:INTRODUCTION:Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. AREAS COVERED:We ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2018.1513490

    authors: Isaacsson Velho P,Carducci MA

    更新日期:2018-10-01 00:00:00

  • Peritoneal carcinomatosis of gastrointestinal origin: natural history and treatment options.

    abstract:BACKGROUND:Peritoneal carcinomatosis (PC) is a challenging consequence of certain malignancies, associated with a poor prognosis and limited treatment options. Generally, PC has been treated similarly to metastatic cancers of the primary tumor, but associated with worse outcomes when compared to other sites of metastat...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780902939151

    authors: Davies JM,O'Neil B

    更新日期:2009-07-01 00:00:00

  • Investigational drugs for head and neck cancer.

    abstract:INTRODUCTION:In the treatment of advanced/metastatic head and neck cancer (HNC), resistance to chemotherapy and to anti-EGFR agents remains a major issue, and new molecular drugs are eagerly awaited. Over the last decade, knowledge of the genetic landscape of HNC has rapidly grown. However, no tailored therapeutic inte...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2016.1175435

    authors: Bossi P,Alfieri S

    更新日期:2016-07-01 00:00:00

  • Therapeutic intervention for Alzheimer's disease with γ-secretase inhibitors: still a viable option?

    abstract:INTRODUCTION:Compounds that inhibit or modulate γ-secretase, the pivotal enzyme which generates β-amyloid (Aβ), are potential therapeutics for Alzheimer's disease (AD). AREAS COVERED:This article briefly reviews the profile of γ-secretase inhibitors that have reached the clinic and discusses the clinical issues surrou...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2011.550572

    authors: Imbimbo BP,Panza F,Frisardi V,Solfrizzi V,D'Onofrio G,Logroscino G,Seripa D,Pilotto A

    更新日期:2011-03-01 00:00:00

  • Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury?

    abstract:INTRODUCTION:The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2013.840287

    authors: Kandilis AN,Karidis NP,Kouraklis G,Patsouris E,Vasileiou I,Theocharis S

    更新日期:2014-01-01 00:00:00

  • Antileukotrienes in clinical development for asthma.

    abstract::Asthma is a serious world health problem characterised by a chronic inflammatory disorder of the airways. Asthma attacks, or exacerbations, are episodic but airway inflammation is chronically present. Thus, this disorder requires long-term management. The goals of asthma management include prevention steps for long-te...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.11.1.49

    authors: Centanni S,Santus P

    更新日期:2002-01-01 00:00:00

  • Clinical complexity of utilizing FGFR inhibitors in cancer therapeutics.

    abstract:INTRODUCTION:Fibroblast growth factor receptors (FGFR 1-4) are a highly conserved family of receptor tyrosine kinases, involved in several physiological processes. Genetic aberrations of FGFRs and their ligands, fibroblast growth factors (FGFs) are involved in several pathological processes including cancer. The FGF-FG...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2020.1838484

    authors: Chandana SR,Babiker HM,Mahadevan D

    更新日期:2020-12-01 00:00:00

  • Tetomilast: new promise for phosphodiesterase-4 inhibitors?

    abstract:INTRODUCTION:Tetomilast is a novel thiazole phosphodiesterase-4 (PDE-4) inhibitor, which may prove useful in both the treatment of inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD). Here, the authors review the pharmacology of the drug, and offer critical review of the available data for...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2012.732065

    authors: Bickston SJ,Snider KR,Kappus MR

    更新日期:2012-12-01 00:00:00

  • Efalizumab for psoriasis?

    abstract::Psoriasis is a chronic skin disorder characterised by inflammation producing red, thickened areas with a flaky white build-up. Efalizumab is a humanised monoclonal IgG1 antibody that inhibits the binding of T lymphocytes to endothelial cells and their subsequent migration. In patients suffering from plaque psoriasis, ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.13.5.551

    authors: Doggrell SA

    更新日期:2004-05-01 00:00:00

  • Novel drugs for renal cell carcinoma.

    abstract:BACKGROUND:Treatment of advanced renal cell carcinoma (RCC) has undergone significant changes over the past 3 years after a long period of relative stagnation. A better understanding of the biology of the tumor led to the discovery of molecular targeted therapies resulting in significant improvement in outcome for this...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.10.1501

    authors: Vakkalanka BK,Bukowski RM

    更新日期:2008-10-01 00:00:00

  • Recent advances in the treatment of epithelial ovarian cancer.

    abstract::Ovarian cancer leads to more fatalities than any other form of gynaecological cancer in North America and Europe. Over the last 30 years survival figures have improved somewhat due to improvements in diagnosis, surgery and chemotherapy. Despite these advances, the majority of patients will die from their disease, with...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.10.9.1715

    authors: Harries M,Kaye SB

    更新日期:2001-09-01 00:00:00

  • A Phase I, Randomized, Double-Blind, Single-Dose, Parallel-Group Study to compare Pharmacokinetic Similarity, Safety, and Immunogenicity Between BAT2506 and Golimumab in Healthy Chinese Male Subjects.

    abstract::Background: To compare the pharmacokinetic (PK) profile, safety, and immunogenicity between golimumab and the biosimilar BAT2506 in healthy Chinese male subjects. Research design and methods: A total of 180 healthy male subjects were recruited for this randomized, double-blinded, single-dose, parallel study. They rece...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2021.1851364

    authors: Wu M,Sun J,Wu D,Xu J,Wei J,Wang Z,Yu J,Li S,Zhang H,Ding Y

    更新日期:2021-01-01 00:00:00

  • Pharmacology of argatroban.

    abstract::Argatroban, a synthetic peptidomimetic antithrombin agent, is the first clinical anticoagulant solely to target thrombin. For some time, this drug has been used in Japan for the management of thromboembolic disorders. Recently, it has been approved in Japan for use in thrombotic and ischaemic stroke. Despite a large n...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.5.625

    authors: Jeske W,Walenga JM,Lewis BE,Fareed J

    更新日期:1999-05-01 00:00:00

  • Novel inhibitors of the early steps of the HIV-1 life cycle.

    abstract::Considerable advances have been made on compounds that are active as inhibitors of HIV entry and fusion. The discovery of chemokines a few years ago focused the attention on coreceptor inhibitors in addition to fusion and attachment blockers. During the last 5 years, there has been an intense research activity from bo...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.16.1.11

    authors: Citterio P,Rusconi S

    更新日期:2007-01-01 00:00:00

  • Inhibitors of cholesteryl ester transfer protein--a new approach to coronary artery disease.

    abstract::Despite the use of the statins to lower low-density lipoprotein-cholesterol, leading to major reductions in the mortality and morbidity that is associated with coronary artery disease, considerable mortality and morbidity remains. Increasing high-density lipoprotein (HDL)-cholesterol levels has been associated with re...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.15.2.99

    authors: Doggrell SA

    更新日期:2006-02-01 00:00:00

  • Pharmacological revascularisation in coronary and peripheral vascular disease.

    abstract::Therapeutic angiogenesis is a novel approach to the treatment of ischaemic or occlusive coronary and peripheral vascular disease. The therapeutic concept is based on the restoration of distal blood flow by the enlargement of existing vessels and tissue perfusion by the induction of new capillaries. Initial studies hav...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.13.10.1319

    authors: Tarzami ST,Singh JP

    更新日期:2004-10-01 00:00:00

  • Gene therapy for Parkinson's disease: review and update.

    abstract::Gene transfer technology is under exploration to find therapies for the treatment of Parkinson's disease (PD) and other neurodegenerative disorders. The technology of genetic transfer can also be used as a neurobiological tool to understand the role of various genes in animal models of neurodegeneration. We describe t...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.10.1551

    authors: Frim DM,Kang UJ

    更新日期:1999-10-01 00:00:00

  • Discontinued drugs in 2006: pulmonary-allergy, dermatological, gastrointestinal and arthritis drugs.

    abstract::This perspective is the second in a series discussing drugs dropped from development in 2006, with a focus on pulmonary-allergy, dermatological, gastrointestinal and arthritis drugs. A survey of discontinued drugs from 2006 is provided, based on data from the Pharmaprojects database, along with an analysis of biology,...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.16.9.1327

    authors: Ozdemir C,Akdis CA

    更新日期:2007-09-01 00:00:00

  • Chronic obstructive pulmonary disease: role of matrix metalloproteases and future challenges of drug therapy.

    abstract::COPD is a chronic disease of the lung that is characterised by decreased air flow and associated abnormal inflammatory responses of the lungs. A total of 80% of COPD incidences are observed in patients with history of smoking tobacco. The chronic condition of COPD is characterised by airway remodelling, which leads to...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.16.7.1069

    authors: Srivastava PK,Dastidar SG,Ray A

    更新日期:2007-07-01 00:00:00

  • The therapeutic potential of the cannabinoids in neuroprotection.

    abstract::After thousands of years of interest the last few decades have seen a huge increase in our knowledge of the cannabinoids and their mode of action. Their potential as medical therapeutics has long been known. However, very real concerns over their safety and efficacy have lead to caution and suspicion when applying the...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.11.10.1365

    authors: Grundy RI

    更新日期:2002-10-01 00:00:00

  • Inhaled insulin using AERx insulin Diabetes Management System (AERx iDMS).

    abstract::Diabetes is a chronic, debilitating disease that afflicts millions of people worldwide and poor glycemic control in this disease leads to numerous microvascular and macrovascular complications. There is growing evidence that tight glycemic control prevents the development, and delays the progression, of microvascular ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.16.10.1673

    authors: Mudaliar S

    更新日期:2007-10-01 00:00:00

  • Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens.

    abstract:BACKGROUND:Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. OBJECTIVE:This drug evaluation foc...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.5.749

    authors: Poulakou G,Giamarellou H

    更新日期:2008-05-01 00:00:00

  • Treatment of hyperlipidaemia with fenofibrate and related fibrates.

    abstract:BACKGROUND:Fenofibrate is the most widely used fibrate. Its efficacy and tolerability in the treatment of hypertriglyceridaemia and combined hyperlipidaemia have been demonstrated in several clinical trials. OBJECTIVE:To review the pharmacology, lipid-lowering and extra-lipid effects of fenofibrate and to preview ABT-...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.10.1599

    authors: Filippatos T,Milionis HJ

    更新日期:2008-10-01 00:00:00

  • Non-nucleoside reverse transcriptase inhibitors: perspectives on novel therapeutic compounds and strategies for the treatment of HIV infection.

    abstract::At present, the nucleoside reverse transcriptase (RT) inhibitors and protease inhibitors (PI) have dominated the therapeutic options for the treatment of human immunodeficiency virus (HIV) infection. From the initial monotherapeutic strategies, to the widely accepted multi-drug cocktails of today, the use of these two...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.10.8.1423

    authors: Buckheit RW

    更新日期:2001-08-01 00:00:00

  • Dasatinib : a novel therapy for breast cancer?

    abstract:INTRODUCTION:Dasatinib is a novel tyrosine kinase inhibitor with activity against the Src family kinases. The Src pathway is active in breast cancer and has been shown to promote cell proliferation, invasiveness, and metastases. Preclinical data support the use of dasatinib to inhibit breast cancer cell growth, modulat...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.2013.793308

    authors: Scher KS,Somlo G

    更新日期:2013-06-01 00:00:00

  • Combination therapy with the type II anti-CD20 antibody obinutuzumab.

    abstract:INTRODUCTION:Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinic...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2017.1373087

    authors: Klein C,Bacac M,Umana P,Fingerle-Rowson G

    更新日期:2017-10-01 00:00:00

  • Therapeutic targets and early stage clinical trials for pulmonary fibrosis.

    abstract:INTRODUCTION:Idiopathic pulmonary fibrosis (IPF) is an age-associated, progressive, and irreversible fatal interstitial lung disease. Although many drugs have failed in clinical trials, these failures improved the understanding of the pathogenesis of IPF. Currently, there are two drugs approved for IPF that slow the pr...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2019.1554054

    authors: Sato S,Yanagihara T,Kolb MRJ

    更新日期:2019-01-01 00:00:00

  • Investigational agents for the treatment of growth hormone-insensitivity syndrome.

    abstract::Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF defic...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.15.4.409

    authors: Kemp SF,Thrailkill KM

    更新日期:2006-04-01 00:00:00