Phosphoinositide 3-kinase α inhibitors: a patent review.

Abstract:

INTRODUCTION:The alpha isoform of the class 1A family of phosphatidylinositol 3-kinases (PI3Kα) has been extensively studied and exploited as a target for cancer drugs. A large number of compounds, from a wide variety of structural scaffolds, are in development. There is an ongoing debate about the desirability for selectivity between PI3Kα and the other isoforms. AREAS COVERED:The article briefly outlines the nature and role of the class 1A PI3K in cell signalling and provides a table of representative inhibitors of these enzymes that have proceeded to clinical trial, with literature data on their isoform selectivity. It covers the published patent literature from 2011 to 2012 (search completed in December 2012), with a particular focus on compounds with a level of selective inhibition of PI3Kα. In most cases, representative examples of claimed compounds and data on their inhibitory effects are provided. EXPERT OPINION:Features of the development of PI3K inhibitors to date have been the plasticity of the enzymes, which possess binding sites for a bewildering number of small molecule scaffolds, and the need to determine the optimal patterns of selectivity between both the PI3K isoforms and the related downstream serine/threonine kinase mammalian target of rapamycin (mTOR) for therapeutic effect. Both themes are apparent in the recent patents reviewed here, with a wide variety of drug types, including variations on existing scaffolds and completely new ones, being evident. While many of these are dual PI3K/mTOR inhibitors, the PI3Kα-selective pyrido[2,3-b]pyrazine heterocycles reported by Intellikine and the (thiazolyl)pyrrolidinecarboxamides of Novartis are of particular interest.

journal_name

Expert Opin Ther Pat

authors

Denny WA

doi

10.1517/13543776.2013.779673

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

789-99

issue

7

eissn

1354-3776

issn

1744-7674

journal_volume

23

pub_type

杂志文章,评审
  • Neuropeptide S receptor ligands: a patent review (2005-2016).

    abstract:INTRODUCTION:Neuropeptide S (NPS) is a 20-residue peptide and endogenous ligand of the NPS receptor (NPSR). This receptor was a formerly orphan GPCR whose activation increases calcium and cyclic adenosine monophosphate levels. The NPS/NPSR system is expressed in several brain regions where it controls important biologi...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2017.1254195

    authors: Ruzza C,Calò G,Di Maro S,Pacifico S,Trapella C,Salvadori S,Preti D,Guerrini R

    更新日期:2017-03-01 00:00:00

  • A decade of nutraceutical patents: where are we now in 2018?

    abstract:INTRODUCTION:In the last 10 years, nutraceuticals have grown in interest to researchers, industry, and consumers and are now familiar in the collective imagination as a tool for preventing the onset of a disease. Often nutraceuticals are confused with biologically active phytochemicals/botanicals which can have health ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2018.1552260

    authors: Daliu P,Santini A,Novellino E

    更新日期:2018-12-01 00:00:00

  • Soluble fms-like tyrosine kinase-1 antibody for diagnosis purposes (WO2010075475).

    abstract:BACKGROUND:The application (WO2010075475) is involved in the diagnosis of angiogenesis-dependent diseases related with the soluble FMS-like tyrosine kinase-1 (sFlt-1) biomarker. OBJECTIVE:It aims to identify, characterize and produce antibodies raised against sFlt-1 for the diagnosis of preeclampsia as well as other c...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1517/13543776.2011.577071

    authors: Boyaud F,Inguimbert N

    更新日期:2011-06-01 00:00:00

  • TBK1 inhibitors: a review of patent literature (2011 - 2014).

    abstract:INTRODUCTION:TANK-binding kinase 1 (TBK1) is a noncanonical IκB kinase family member that regulates the innate immune response. Misregulation of TBK1 activity can promote inflammatory disorders and oncogenesis; therefore, TBK1 inhibitors are considered a promising therapy for inflammation and cancer. AREAS COVERED:In ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2015.1081168

    authors: Yu T,Yang Y,Yin DQ,Hong S,Son YJ,Kim JH,Cho JY

    更新日期:2015-01-01 00:00:00

  • New β-glucan inhibitors as antifungal drugs.

    abstract:INTRODUCTION:New classes of synthetic and semi-synthetic β-glucan inhibitors have recently emerged, providing analogs that, in some cases, have been proven to have a high degree of activity against fungi, offering the prospect of alternatives to the commercially available lipopeptide/echinocandin agents caspofungin, mi...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2011.603899

    authors: Hector RF,Bierer DE

    更新日期:2011-10-01 00:00:00

  • Novel glucokinase activators: a patent review (2008 - 2010).

    abstract:IMPORTANCE OF THE FIELD:Small molecule glucokinase activators (GKAs) continue to represent a potential strategy to treat type 2 diabetes (T2D). Glucokinase (GK) primarily exerts its effect through modulatory actions in pancreatic β-cells and hepatocytes. It couples insulin secretion in the pancreas with plasma glucose ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2011.542413

    authors: Sarabu R,Berthel SJ,Kester RF,Tilley JW

    更新日期:2011-01-01 00:00:00

  • Parthenogenetically activated human oocytes and parthenogenetic embryonic stem cells: US20100233143.

    abstract:BACKGROUND:The application (US20100233143) is in the field of embryonic stems cells (ESCs) and the generation of ESCs from parthenogenetically activated human oocytes. OBJECTIVE:It aims at determining optimal conditions for parthenogenetically activating human oocytes. METHODS:Oocytes isolated from female donors were...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2011.581230

    authors: Taupin P

    更新日期:2011-08-01 00:00:00

  • Phosphodiesterase 10 (PDE10) inhibitors: an updated patent review (2014-present).

    abstract::Introduction: Phosphodiesterase 10 (PDE10) is one of at least 11 different PDE families, which are the enzymes that degrade adenosine 3',5'-cyclic monophosphate (cAMP) and/or guanosine 3',5'-cyclic monophosphate (cGMP) by hydrolyzing the phosphodiester bonds. Inhibition of PDE10A represents a molecular target in the t...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2020.1709444

    authors: Zagórska A

    更新日期:2020-02-01 00:00:00

  • Small molecule c-Met kinase inhibitors: a review of recent patents.

    abstract:IMPORTANCE OF THE FIELD:c-Met kinase is the receptor for hepatocyte growth factor. Primarily expressed on epithelial and mesenchymal cells its normal function is associated with wound healing, liver regeneration and embryo development. However, dysregulation of c-Met through overexpression, gene amplification, mutation...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543770903514137

    authors: Porter J

    更新日期:2010-02-01 00:00:00

  • Exendins and exendin analogs for diabetic therapy: a patent review (2012-2015).

    abstract:INTRODUCTION:Since exendin-4 (exenatide) was approved for diabetes therapy in 2005, several exendin analogs have been developed for the treatment of type 2 diabetes mellitus. As exenatide is a relatively short-acting injectable agent, major approaches have focused on developing long-acting exendin analogs to improve pa...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2016.1192130

    authors: Park EJ,Lim SM,Lee KC,Na DH

    更新日期:2016-07-01 00:00:00

  • Cancer immunotherapy using anti-TIM3/PD-1 bispecific antibody: a patent evaluation of EP3356411A1.

    abstract::Introduction: TIM3 and PD-1 are checkpoint inhibitors in cancer that coordinate the downregulation of the proliferation of antigen-specific lymphocytes. There is a great need to discover and develop new therapies focused on inhibiting the action of TIM3 and PD-1 and consequently improving the immune response in the va...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2019.1637422

    authors: Herrera-Camacho I,Anaya-Ruiz M,Perez-Santos M,Millán-Pérez Peña L,Bandala C,Landeta G

    更新日期:2019-08-01 00:00:00

  • Dendrimer and cancer: a patent review (2006-present).

    abstract:INTRODUCTION:Dendrimers were widely used in cancer diagnosis and therapy during the past decade. The surface functionalities allow bioactive molecules such as imaging probes, therapeutic compounds, targeting ligands to be present on dendrimer surface in a multivalent fashion. In addition, the interior pockets as well a...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2013.761207

    authors: Cai X,Hu J,Xiao J,Cheng Y

    更新日期:2013-04-01 00:00:00

  • Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).

    abstract:INTRODUCTION:The cyclic nucleotides cAMP and cGMP are ubiquitous intracellular second messengers regulating a large variety of biological processes. The intracellular concentration of these biologically relevant molecules is modulated by the activity of phosphodiesterases (PDEs), a class of enzymes that is grouped in 1...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2016.1203902

    authors: Trabanco AA,Buijnsters P,Rombouts FJ

    更新日期:2016-08-01 00:00:00

  • Novel compound, organic cation transporter 3 detection agent and organic cation transporter 3 activity inhibitor, WO2015002150 A1: a patent evaluation.

    abstract::Increasing pharmacological studies have demonstrated that organic cation transporter 3 (OCT3) plays an important role in controlling the extracellular concentrations of released monoamine neurotransmitter, suggesting that OCT3 might be a promising target in the treatment of depression. As a consequence, compounds show...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1080/13543776.2016.1180364

    authors: Hu T,Wang L,Pan X,Qi H

    更新日期:2016-08-01 00:00:00

  • A patent review on the development of human cytochrome P450 inhibitors.

    abstract:INTRODUCTION:CYP, a ubiquitous superfamily of enzymes expressed in major organs in humans, plays a key role in biosynthesis of steroids and metabolism of xenobiotics. Inhibitors of these vital enzymes provide, as tools, the opportunity to gain an insight to their role in a myriad of bioactivity and to intervene as ther...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2014.899583

    authors: Francis S,Delgoda R

    更新日期:2014-06-01 00:00:00

  • Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers: WO2010066840.

    abstract::This article evaluates a patent application from Solvay Pharmaceuticals, which claims spiro azepane-oxazolidinones as novel blockers of the voltage-gated potassium channel Kv1.3 for the treatment of diabetes, psoriasis, obesity, transplant rejection and T-cell mediated autoimmune diseases such as rheumatoid arthritis ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1517/13543776.2010.528392

    authors: Wulff H

    更新日期:2010-12-01 00:00:00

  • Progress in the discovery and development of small-molecule modulators of G-protein-coupled receptor 40 (GPR40/FFA1/FFAR1): an emerging target for type 2 diabetes.

    abstract:BACKGROUND:The family of G-protein-coupled receptors (GPCRs) serves as the target for almost a third of currently marketed drugs and provides the predominant mechanism through which extracellular factors transmit signals to the cell. GPCRs have been proved to be good therapeutic targets for metabolic disorders. In rece...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543770802665717

    authors: Bharate SB,Nemmani KV,Vishwakarma RA

    更新日期:2009-02-01 00:00:00

  • ATP-competitive DNA gyrase and topoisomerase IV inhibitors as antibacterial agents.

    abstract:INTRODUCTION:The bacterial topoisomerases DNA gyrase and topoisomerase IV are validated targets for development of novel antibacterial agents. Fluoroquinolones inhibit the catalytic GyrA and/or ParC(GrlA) subunit and have been commonly used, although these have toxicity liabilities that restrict their use. The ATPase G...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2019.1575362

    authors: Durcik M,Tomašič T,Zidar N,Zega A,Kikelj D,Mašič LP,Ilaš J

    更新日期:2019-03-01 00:00:00

  • 3-Hydroxy-3-methylglutaryl-coenzyme A reductase modulator: toward age- and sex-personalized medicine.

    abstract::Cholesterol homeostasis maintenance is regulated by a cellular feedback system that senses cholesterol amount in cellular membranes. 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) plays a pivotal role in cholesterol metabolism as it is the key rate-limiting enzyme of its biosynthetic pathway; its inhibition pr...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1517/13543776.2015.1061996

    authors: Pallottini V

    更新日期:2015-01-01 00:00:00

  • New hexahydrodiazocino-naphthyridine triones as HIV-1 integrase inhibitors: WO2008048538 A1.

    abstract::Since the discovery of MK-0518 (raltegravir, the first FDA-approved integrase inhibitor) in October 2007, Merck Co. researchers have continued to patent original new heterocycles related to raltegravir as powerful strand transfer inhibitors. Among the most recent patented works hexahydrodiazocino-naphthyridinetriones ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1517/13543770802603577

    authors: Cotelle P

    更新日期:2009-01-01 00:00:00

  • Antimicrobial peptides (AMPs) as drug candidates: a patent review (2003-2015).

    abstract:INTRODUCTION:Antimicrobial peptides (AMPs) represent the large group of endogenous compounds widely distributed in nature. Due to their broad spectrum of antibiotic activity, as well as anti-inflammatory and immunomodulatory properties, AMPs became a model for the discovery of novel antimicrobial drugs that could answe...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2016.1176149

    authors: Kosikowska P,Lesner A

    更新日期:2016-06-01 00:00:00

  • Therapeutic inhibition of the renin angiotensin aldosterone system.

    abstract:BACKGROUND:Inhibitors of the renin angiotensin aldosterone system (RAAS) represent some of the most widely prescribed, successful and well-tolerated therapeutics of recent times and are of proven worth in the management/prevention of cardiovascular disease and diabetic nephropathy. However, as knowledge has grown about...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543770903008536

    authors: Laight DW

    更新日期:2009-06-01 00:00:00

  • Patented small molecule inhibitors of p53-MDM2 interaction.

    abstract::The interaction between p53 and murine double minute 2 (MDM2) provides an attractive drug target in oncology. Small molecule inhibitors of this interaction have not only provided strong evidence for blocking the protein-protein interaction, but are also extremely useful as biological probes and ultimately as novel the...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1517/13543776.16.2.165

    authors: Deng J,Dayam R,Neamati N

    更新日期:2006-02-01 00:00:00

  • 5-Lipoxygenase inhibitors: a review of recent developments and patents.

    abstract:IMPORTANCE TO THE FIELD:Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543771003602012

    authors: Pergola C,Werz O

    更新日期:2010-03-01 00:00:00

  • T-type calcium channels inhibitors: a patent review.

    abstract:IMPORTANCE OF THE FIELD:T-type calcium channels are transmembrane proteins that regulate calcium entry in the cell in a voltage-dependent manner. Intracellular calcium levels are the key to many physiological processes, ranging from neuron firing to cardiac pacemaking. Inhibition of T-type calcium channels is heralded ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2011.536532

    authors: Giordanetto F,Knerr L,Wållberg A

    更新日期:2011-01-01 00:00:00

  • Novel pharmacological modulators of autophagy: an updated patent review (2012-2015).

    abstract:INTRODUCTION:Autophagy is a lysosome-dependent degradation pathway that maintains cellular homeostasis in response to a variety of cellular stresses. Accumulating reports based on animal models have indicated the importance of this catabolic program in many human pathophysiological conditions, including diabetes, neuro...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2016.1217996

    authors: Ha J,Kim J

    更新日期:2016-11-01 00:00:00

  • Lessons from black pepper: piperine and derivatives thereof.

    abstract:INTRODUCTION:Piperine is a simple and pungent alkaloid found in the seeds of black pepper (Piper nigrum). Following its isolation and full characterization, the biological properties of piperine have been extensively studied, and piperine-like derivatives have shown an interesting range of pharmacological activities. I...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1517/13543776.2016.1118057

    authors: Chavarria D,Silva T,Magalhães e Silva D,Remião F,Borges F

    更新日期:2016-01-01 00:00:00

  • Microneedles as an alternative technology for transdermal drug delivery systems: a patent review.

    abstract::Introduction: The most conventional drug delivery systems exist with limitations such as drug degradation, toxicity and low bioavailability. Also, hypodermic injections can cause pain, compromising patient compliance. Due to this, transdermal drug delivery systems can minimize several problems associated with conventi...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章,评审

    doi:10.1080/13543776.2020.1742324

    authors: Queiroz MLB,Shanmugam S,Santos LNS,Campos CA,Santos AM,Batista MS,Araújo AAS,Serafini MR

    更新日期:2020-06-01 00:00:00

  • Novel 1,5-naphthyridine PI3Kδ inhibitors, an evaluation of WO2011075628.

    abstract::A small series of aryl(1-arylamino)ethyl,1,5-naphthyridine derivatives that selectively inhibit PI3Kδ was prepared. The compounds are claimed to be useful in the treatment of cancer, inflammatory and autoimmune diseases. The compounds represent further variations around a structural motif explored in a number of previ...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1517/13543776.2011.622749

    authors: Norman P

    更新日期:2011-11-01 00:00:00

  • Pharmaceutical agents for treatment of leishmaniasis: a patent landscape.

    abstract:INTRODUCTION:Leishmaniasis is a neglected tropical disease caused by protozoa of the genus Leishmania. Worldwide, approximately 1.5-2 million new cases of leishmaniasis and 20,000-30,000 deaths occurs each year. Effective treatment for all forms of leishmaniasis have numerous adverse effects contributing to poor adhere...

    journal_title:Expert opinion on therapeutic patents

    pub_type: 杂志文章

    doi:10.1080/13543776.2020.1789100

    authors: Barbosa Gomes de Carvalho YM,Shanmugam S,Batista MS,Serafini MR,Araújo AAS,Quintans Júnior LJ

    更新日期:2020-08-01 00:00:00