Medical treatment that
targets human proteins rather than ever - mutating viruses may one day help HIV - positive people whose bodies have built a resistance to «cocktails» currently used to keep them healthy, according to a Keck School of Medicine of USC researcher.
«New way to treat HIV identified:
Targeting human proteins may be more effective than the use of «HIV cocktails» to maintain health.»
Not exact matches
«
Proteins that appear to have neurodevelopmental significance for
human babies will be key
targets for future research focused on enhancing infant formula,» Lemay said.
The drug - like compounds can be modified and developed into medicines that
target a
protein in the
human body that is responsible for chemotherapy resistance in cancers, said biochemist Pia D. Vogel, lead author on the scientific paper reporting the discovery.
The largest class of
human target proteins for drugs are the so - called G -
protein - coupled receptors.
Approaches based on these five strategies have been used for streamlined, enhanced validation of more than 10,000 antibodies from more than 30 providers,
targeting over 7,000
human proteins as part of the Human Protein Atlas pro
human proteins as part of the
Human Protein Atlas pro
Human Protein Atlas program.
As a result of these steps, the team could detect the copies of the
target protein, even though
human proteins were 10 million times more plentiful.
«This is the first time that this specific
protein -
protein signaling complex has been identified in GBM, and it gives us a new potential
target for drug development,» says Fisher, Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at VCU Massey, professor and chair of the Department of
Human and Molecular Genetics at the VCU School of Medicine, and director of the VIMM.
Mathias Uhlen, director of the
Human Protein Atlas project and co-author of the paper, says: «I am extremely pleased that the resource created through the
Human Protein Atlas effort has been used in the analysis of clinical data obtained from liver disease patients and that this analysis has led to the identification of liver - specific drug
targets that can be used for treatment of this clinically important patient group.»
DEADLY
TARGET A
human immune
protein might combat the MERS virus, shown here in yellow in a camel's cells.
To track down the location of
proteins inside
human tissues, Uhlén's team of about 100 scientists breaks the problem into two parts — finding antibodies that
target individual
proteins and then using those antibodies to hunt for
proteins inside tissues.
Insight into this mechanism led the researchers to design new peptides — snippets of the
human B7 - 2 receptor
protein — that powerfully block the binding of a superantigen to its costimulatory receptor
targets, and thereby protect against lethal toxic shock, as they showed in animals.
Mardinoglu says the team's network modeling approach, which relied on data from the Sweden - based
Human Protein Atlas project and The Genotype - Tissue Expression (GTEx) project consortia, can be used in the identification of drug
targets and eventually in the development of efficient strategies for treating a number of chronic liver diseases.
SAMHD1, a
human protein, plays a major role in HIV's devastation of the immune system and is rarely mutated, so we are hopeful that it will be a better
target for therapies.»
There are over 500 known
human kinases and 10s of thousands of possible
proteins they can
target.
«
Proteins that appear to have neurodevelopmental significance for
human babies will be key
targets for future research focused on enhancing infant formula,» Lemay said.
The team believed that because these
proteins might be exposed on the surface of the membrane, they could conceivably be
targeted by the
human immune system.
This is why it is so difficult for
humans to mount an effective immune response and why it is challenging for researchers to develop vaccines
targeting the HIV envelope
proteins,» Dr. Blanchard says.
Proteins in this spider's venom
target the nervous system of insects but leave
humans unharmed.
«As in the mouse,» he continues, «the
human elements can be used in biotechnological applications to
target mRNA encoding different
proteins, by simply engineering the antisense part.
«Our research adds weight to the idea that effective antifungal drugs can
target even those mitochondrial
proteins that are highly conserved in
humans and fungi, and that this could be a way to make a broad spectrum antifungal combination therapy that would be less susceptible to resistance,» says Benjamin Vincent, a former graduate student in Whitehead Member Susan Lindquist's lab who is now a scientist at Yumanity Therapeutics.
«If this same alternative ubiquitination process occurs in
humans, perhaps an engineered ubiquitin - editing
protein could be developed to
target and control processes critical to the development of many diseases, including infection,» Luo said.
Protein interactions between viruses and cells can illuminate common weak points in
human biology and reveal potential new
targets for antiviral treatments
Human cytomegalovirus major immediate early 1
protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface.
Mass spectrometry ‐ based cellular thermal shift assay (MS ‐ CeTSA) analysis of CDK4 / 6 inhibitor palbociclib
targets in MCF7
human breast cancer cells identifies
protein complexes including the 20S proteasome.
Proteins targeted for structure determination by SSGCID are selected for their biomedical relevance in
human pathogens such as Ebola and Zika, as well as those responsible for tuberculosis, leprosy, malaria, and influenza.
Phenylalanine pairs capable of forming a molecular switch are also present in many other signaling
proteins, including receptors in
human cells, making it an attractive
target for drug design and biotechnology applications.
The IT -
Targets project provides a unique opportunity to explore the roles of G
protein - coupled receptors in
human tumor immunology.
The AstraZeneca annotated library consists of roughly 14,000 compounds specifically
targeting over 1,700
human proteins.
Therefore, Teitell's group opted to further modify their constructs with a 3 ′ - UTR mitochondrial
targeting sequence (MTS) from
human mitochondrial ribosomal
protein S12 — the same essential approach used to optimize the import of allotopically - expressed
proteins by Dr. Marisol Corral - Debrinski, (3,4) and subsequently advanced for multiple additional ETS subunit
proteins by Dr. Matthew O'Connor's group at the SENS Foundation Research Center (RC).
Other theories and lines of research have begun to prosper due to the lack of tangible
human results for anti-amyloid immunotherapies, in particular that neurofibrillary tangles of misfolded tau
protein are just as much a
target for clearance as is amyloid - β, and that perhaps it is time to focus on the decline of known clearance mechanisms rather than the amyloid itself.
We believe that leveraging
human intuition through creation of a scientific game for drug discovery can not only provide a new avenue to discover therapeutic drugs for
protein targets, but can also contribute to the development of new sophisticated algorithms to use in computer aided drug design.
A
protein displayed on the surface of malaria parasites called «TRAP» is a high - priority vaccine
target, but how it interacts with
human... -LSB-...]
Each uses a different approach to
targeting these malformed
proteins, and is supported by data in animal models — and the early
human evidence looks favorable, if very preliminary.
To find out, the researchers looked at the relationships between 919 successful drugs, their
human gene or
protein targets, and the functional properties of those
targets.
Zheng is now trying to translate this finding to
human pathology, where mutations in
human ubiquitin ligases cause low affinity bindings to
target proteins.
In the case of Influenza A, the loss of RNA exosome activity severely compromises viral infectivity, but also manifests in
human neurodegeneration suggesting that viruses
target essential
proteins implicated in rare disease in order to ensure continual adaptation.
CAR - T cells are
human killer T cells artificially engineered to
target specific
proteins (antigens) associated with a cancer.
«Seeing this drug bound to its intended
human protein target at atomic resolution was mind - blowing,» said Frost, an assistant professor of biochemistry and biophysics at UCSF.
Susan Amara, USA - «Regulation of transporter function and trafficking by amphetamines, Structure - function relationships in excitatory amino acid transporters (EAATs), Modulation of dopamine transporters (DAT) by GPCRs, Genetics and functional analyses of
human trace amine receptors» Tom I. Bonner, USA (Past Core Member)- Genomics, G
protein coupled receptors Michel Bouvier, Canada - Molecular Pharmacology of G
protein - Coupled Receptors; Molecular mechanisms controlling the selectivity and efficacy of GPCR signalling Thomas Burris, USA - Nuclear Receptor Pharmacology and Drug Discovery William A. Catterall, USA (Past Core Member)- The Molecular Basis of Electrical Excitability Steven Charlton, UK - Molecular Pharmacology and Drug Discovery Moses Chao, USA - Mechanisms of Neurotophin Receptor Signaling Mark Coles, UK - Cellular differentiation,
human embryonic stem cells, stromal cells, haematopoietic stem cells, organogenesis, lymphoid microenvironments, develomental immunology Steven L. Colletti, USA Graham L Collingridge, UK Philippe Delerive, France - Metabolic Research (diabetes, obesity, non-alcoholic fatty liver, cardio - vascular diseases, nuclear hormone receptor, GPCRs, kinases) Sir Colin T. Dollery, UK (Founder and Past Core Member) Richard M. Eglen, UK Stephen M. Foord, UK David Gloriam, Denmark - GPCRs, databases, computational drug design, orphan recetpors Gillian Gray, UK Debbie Hay, New Zealand - G
protein - coupled receptors, peptide receptors, CGRP, Amylin, Adrenomedullin, Migraine, Diabetes / obesity Allyn C. Howlett, USA Franz Hofmann, Germany - Voltage dependent calcium channels and the positive inotropic effect of beta adrenergic stimulation; cardiovascular function of cGMP
protein kinase Yu Huang, Hong Kong - Endothelial and Metabolic Dysfunction, and Novel Biomarkers in Diabetes, Hypertension, Dyslipidemia and Estrogen Deficiency, Endothelium - derived Contracting Factors in the Regulation of Vascular Tone, Adipose Tissue Regulation of Vascular Function in Obesity, Diabetes and Hypertension, Pharmacological Characterization of New Anti-diabetic and Anti-hypertensive Drugs, Hypotensive and antioxidant Actions of Biologically Active Components of Traditional Chinese Herbs and Natural Plants including Polypehnols and Ginsenosides Adriaan P. IJzerman, The Netherlands - G
protein - coupled receptors; allosteric modulation; binding kinetics Michael F Jarvis, USA - Purines and Purinergic Receptors and Voltage-gated ion channel (sodium and calcium) pharmacology Pain mechanisms Research Reproducibility Bong - Kiun Kaang, Korea - G
protein - coupled receptors; Glutamate receptors; Neuropsychiatric disorders Eamonn Kelly, Prof, UK - Molecular Pharmacology of G
protein - coupled receptors, in particular opioid receptors, regulation of GPCRs by kinasis and arrestins Terry Kenakin, USA - Drug receptor pharmacodynamics, receptor theory Janos Kiss, Hungary - Neurodegenerative disorders, Alzheimer's disease Stefan Knapp, Germany - Rational design of highly selective inhibitors (so call chemical probes)
targeting protein kinases as well as
protein interaction inhibitors of the bromodomain family Andrew Knight, UK Chris Langmead, Australia - Drug discovery, GPCRs, neuroscience and analytical pharmacology Vincent Laudet, France (Past Core Member)- Evolution of the Nuclear Receptor / Ligand couple Margaret R. MacLean, UK - Serotonin, endothelin, estrogen, microRNAs and pulmonary hyperten Neil Marrion, UK - Calcium - activated potassium channels, neuronal excitability Fiona Marshall, UK - GPCR molecular pharmacology, structure and drug discovery Alistair Mathie, UK - Ion channel structure, function and regulation, pain and the nervous system Ian McGrath, UK - Adrenoceptors; autonomic transmission; vascular pharmacology Graeme Milligan, UK - Structure, function and regulation of G
protein - coupled receptors Richard Neubig, USA (Past Core Member)- G
protein signaling; academic drug discovery Stefan Offermanns, Germany - G
protein - coupled receptors, vascular / metabolic signaling Richard Olsen, USA - Structure and function of GABA - A receptors; mode of action of GABAergic drugs including general anesthetics and ethanol Jean - Philippe Pin, France (Past Core Member)- GPCR - mGLuR - GABAB - structure function relationship - pharmacology - biophysics Helgi Schiöth, Sweden David Searls, USA - Bioinformatics Graeme Semple, USA - GPCR Medicinal Chemistry Patrick M. Sexton, Australia - G
protein - coupled receptors Roland Staal, USA - Microglia and neuroinflammation in neuropathic pain and neurological disorders Bart Staels, France - Nuclear receptor signaling in metabolic and cardiovascular diseases Katerina Tiligada, Greece - Immunopharmacology, histamine, histamine receptors, hypersensitivity, drug allergy, inflammation Georg Terstappen, Germany - Drug discovery for neurodegenerative diseases with a focus on AD Mary Vore, USA - Activity and regulation of expression and function of the ATP - binding cassette (ABC) transporters
Abbreviations: Aβ, amyloid β - peptide; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; Ambra1, activating molecule in Beclin -1-regulated autophagy; AMPK, AMP - activated
protein kinase; APP, amyloid precursor
protein; AR, androgen receptor; Atg, autophagy - related; AV, autophagic vacuole; Bcl, B - cell lymphoma; BH3, Bcl - 2 homology 3; CaMKKβ, Ca2 + - dependent
protein kinase kinase β; CHMP2B, charged multivesicular body
protein 2B; CMA, chaperone - mediated autophagy; 2 ′ 5 ′ ddA, 2 ′, 5 ′ - dideoxyadenosine; deptor, DEP - domain containing mTOR - interacting
protein; DRPLA, dentatorubral pallidoluysian atrophy; 4E - BP1, translation initiation factor 4E - binding
protein - 1; Epac, exchange
protein directly activated by cAMP; ER, endoplasmic reticulum; ERK1 / 2, extracellular - signal - regulated kinase 1/2; ESCRT, endosomal sorting complex required for transport; FAD, familial AD; FDA, U.S. Food and Drug Administration; FIP200, focal adhesion kinase family - interacting
protein of 200 kDa; FoxO3, forkhead box O3; FTD, frontotemporal dementia; FTD3, FTD linked to chromosome 3; GAP, GTPase - activating
protein; GR, guanidine retinoid; GSK3, glycogen synthase kinase 3; HD, Huntington's disease; hiPSC,
human induced pluripotent stem cell; hVps, mammalian vacuolar
protein sorting homologue; IKK, inhibitor of nuclear factor κB kinase; IMPase, inositol monophosphatase; IP3R, Ins (1,4,5) P3 receptor; I1R, imidazoline - 1 receptor; JNK1, c - Jun N - terminal kinase 1; LC3, light chain 3; LD, Lafora disease; L - NAME, NG - nitro - L - arginine methyl ester; LRRK2, leucine - rich repeat kinase 2; MIPS, myo - inositol -1-phosphate synthase; mLST8, mammalian lethal with SEC13
protein 8; MND, motor neuron disease; mTOR, mammalian
target of rapamycin; mTORC, mTOR complex; MVB, multivesicular body; NAC, N - acetylcysteine; NBR1, neighbour of BRCA1 gene 1; NOS, nitric oxide synthase; p70S6K, ribosomal
protein S6 kinase - 1; PD, Parkinson's disease; PDK1, phosphoinositide - dependent kinase 1; PE, phosphatidylethanolamine; PI3K, phosphoinositide 3 - kinase; PI3KC1a, class Ia PI3K; PI3KC3, class III PI3K; PI3KK, PI3K - related
protein kinase; PINK1, PTEN - induced kinase 1; PKA,
protein kinase A; PLC, phospholipase C; polyQ, polyglutamine; PS, presenilin; PTEN, phosphatase and tensin homologue deleted from chromosome 10; Rag, Ras - related GTP - binding
protein; raptor, regulatory - associated
protein of mTOR; Rheb, Ras homologue enriched in brain; rictor, rapamycin - insensitive companion of mTOR; SBMA, spinobulbar muscular atrophy; SCA, spinocerebellar ataxia; SLC, solute carrier; SMER, small - molecule enhancer of rapamycin; SMIR, small - molecule inhibitor of rapamycin; SNARE, N - ethylmaleimide - sensitive factor - attachment
protein receptor; SOD1, copper / zinc superoxide dismutase 1; TFEB, transcription factor EB; TOR,
target of rapamycin; TSC, tuberous sclerosis complex; ULK1, UNC -51-like kinase 1; UVRAG, UV irradiation resistance - associated gene; VAMP, vesicle - associated membrane
protein; v - ATPase, vacuolar H + - ATPase; Vps, vacuolar
protein sorting
The scientists report in the September 24 issue of Molecular Cell that the
protein, called fatty acid transporter
protein - 4 (FATP4), may constitute a novel
target for anti-obesity therapy in
humans.
In collaboration with Nanyang Technological University, experiments were also conducted to co-deliver paclitaxel and small interfering RNA (siRNA)
targeting a
protein that prevents cell death (Bcl - 2) to MDA - MB - 231
human breast cancer cell line.
Furthermore, sgRNA
targeting GPI anchor
protein pathway genes induced loss of function mutations in
human and mouse cell lines measured by FLAER labelling.
The GCS - 100
targets the
protein galectin - 3, which, when overproduced by the
human body, has been associated with chronic organ failure and cancer.