Caspase 2 (CASP2, CASP-2, ICH1, NEDD-2, NEDD2, PPP1R57) is an initiator caspase for cellular apoptosis. It is also involved in several other vital processes including oxidative stress responses, regulation of cell cycle checkpoints, autophagy and senescence. Disorders of CASP2 activity are observed at obesity, metabolic syndrome, nonalcoholic fatty liver disease and cancer [1, 2]. Therefore, small molecule compounds modulating CASP2 activity may have significant therapeutic potential.
|
Read more...
|
Selective estrogen receptor modulators (SERMs) are compounds that act on the estrogen receptors (ERs). A characteristic that distinguishes these substances from pure ER antagonists and agonists (silent antagonists and full agonists) is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.
|
Read more...
|
Transporters are proteins that span the plasma membrane and regulate the traffic of small molecules in and out of the cell. They play a particularly important role in chemical signalling between neurons in the CNS, where they act to control the concentration of neurotransmitters in the synapse. Another key role for transporters is in excluding undesirable xenobiotics from the cell, whilst allowing key molecules required for the cell life cycle to enter. The majority of transporters are targets for drug discovery.
|
Read more...
|
Estrogen-related receptor gamma (ERRγ) is involved in energy metabolism, mitochondrial functions, biogenesis and tissue repair. Disorders of ERRγ are observed at type 2 diabetes, hypoxia, metabolic syndrome and cancer. Therefore, small molecule compounds modulating ERRγ activity may have significant therapeutic potential.
|
Read more...
|
The SH2 (Src Homology 2) domains play key roles in different kinase-mediated intracellular signal transduction pathways and many human diseases are associated with their dysregulation [1-3].
|
Read more...
|
Caseinolytic protease (ClpP) found in the human mitochondria is a major member of mitochondrial protein quality control system. This serine protease removes damaged or misfolded proteins in mitochondrial matrix. It is overexpressed in a wide range of acute myeloid leukemia (AML) cases and not in normal hematopoietic precursors [1].
|
Read more...
|
Phenotypic drug discovery is successful strategy that allows to identify substances (small molecules, peptides etc.) which alter the phenotype of cells, tissues or whole organisms in a desired manner.
|
Read more...
|
Poly (ADP-ribose) Polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly(ADP-ribose) synthase 1 is an enzyme that modifying nuclear proteins by poly ADP-ribosylation. PARP-1 is involved in modulating DNA repair, DNA replication, transcription, DNA methylation and chromatin remodeling through PARylation of downstream proteins. Also it is involved in differentiation, proliferation, tumor transformation and may participate in the pathophysiology of type I diabetes [1, 2].
|
Read more...
|
Targeting protein protein interaction (PPI) is a new challenge to current drug discovery. Due to growing interest in PPI inhibitors we represent focused compound libraries covering chemical space of PPI inhibitors.
|
Read more...
|
Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase binding protein or cluster of differentiation 26 (CD26), is a serine exopeptidase able to recognizes an amino acid sequence having proline at the N-terminal penultimate position and inactivate this oligopeptides through the removal of N-terminal proline dipeptides [1, 2].
|
Read more...
|
|
The GABA receptors (GABAA and GABAB) respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. GABA receptors agonists produce typically sedative effects, and may also cause other effects such as anticonvulsant, anxiolytic and muscle relaxant effects. Antagonists of GABA receptors inhibit the action of GABA. In general they produce stimulant and convulsant effects. Therefore, small molecule compounds modulating GABA receptors activity may have significant therapeutic potential.
|
Read more...
|
Beta-arrestins (ß-arrestin 1 and ß-arrestin 2) play central roles in the mechanisms regulating G protein-coupled receptors signalling and trafficking. They participate in agonist-mediated desensitization of GPCR and cause specific dampening of cellular responses to stimuli such as sensory signals, hormones or neurotransmitters [1].
|
Read more...
|
Nuclear estrogen receptors (ERα and Erβ) are members of the nuclear receptor family of intracellular receptors. Estrogen receptors (ERs) are involved in modulation of biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism and behavior in both females and males.
|
Read more...
|
Alzheimer's disease (AD) is a complex neurodegenerative disorder of the central nervous system that usually starts slowly and gets worse over time. It is characterized by progressive loss of dementia, cognitive ability, and eventually death. Currently there is no cure for the disease.
|
Read more...
|
Epigenetic targets are a major new category for successful drug research. Among them the protein methyltransferases (PMTs) which have crucial roles in gene transcription are an important group of enzymes that play key parts in normal physiology and human diseases. There has been a significant increase in attention towards protein arginine methyltransferases (PRMTs) which catalyze methylation of nitrogen of specific arginine residues in proteins and impact on numerous essential biological pathways by methylating different nuclear, cytoplasmic and membrane protein substrates.
|
Read more...
|
The recent substantial progress in RNA biology underscores the importance of RNA in normal and aberrant cellular functions. Rather, it is now recognized that RNA is essential for transcriptional regulation, translational regulation, protein function, and catalysis, responsibilities that have classically been reserved for proteins.
|
Read more...
|
A neurotoxic peptide β-amyloid (Aβ) is linked to the beginning of Alzheimer’s disease (AD). The accumulation of amyloid-beta inside mitochondria boosts production of free radical and activation of the apoptotic pathway. Human Presequence Protease (hPreP, PITRM1) is a mitochondrial ATP-independent metalloprotease. It degrades toxic peptides, including mitochondrial presequences and β-amyloid. This enzyme is an attractive target for Alzheimer’s disease drug design because enhancement of it's activity increases the level of Aβ proteolysis.
|
Read more...
|
5-hydroxytryptamine receptors (serotonin receptors , 5-HT receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels found in the central and peripheral nervous systems [1, 2]. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.
|
Read more...
|
The sodium glucose cotransporter 2 (SGLT2) reabsorbs most of the glucose filtered by the kidneys. SGLT2 inhibitors reduce glucose reabsorption, thereby lowering blood glucose levels in patients with diabetes [1]. Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality.
|
Read more...
|
The enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A, HMG-CoA, HMGCR) catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis. The HMG-CoA reductase inhibitors, also known as statins, are the most effective class of drugs for lowering serum low-density lipoprotein cholesterol concentrations.
|
Read more...
|
|