Breaking News
October 22, 2018 - Researchers discover how acne-causing bacteria resist treatment
October 22, 2018 - Cancer trial shows treating the prostate with radiotherapy improves survival
October 22, 2018 - New hope for a drug to treat lymphedema symptoms
October 22, 2018 - Immune-Based Treatment Helps Fight Aggressive Breast Cancer, Study Finds
October 22, 2018 - Takeda announces positive Phase 3 ALTA-1L data in first-line therapy for advanced ALK+ NSCLC
October 22, 2018 - Paternal exercise has significant impact on child’s lifelong metabolic health
October 22, 2018 - Targeting specific genomic mutation in breast cancer improves survival
October 22, 2018 - Loss of tumor protein p53 helps cancer cells grow in hostile environment
October 22, 2018 - IDT to demonstrate CRISPR expertise at European-focused events
October 22, 2018 - Breathing through the nose improves memory consolidation
October 22, 2018 - Recreational Marijuana Now Legal in Canada
October 22, 2018 - Scientists reveal drumming helps schoolchildren diagnosed with autism
October 22, 2018 - A stage IV cancer patient discusses what it means to live well with serious illness
October 22, 2018 - In Kids with Autism, Short Questionnaire May Detect GI Disorders
October 22, 2018 - Merck presents MK-1454 Phase 1 data for treatment of advanced solid tumors or lymphomas
October 22, 2018 - Aspirin may be effective in preventing blood clots after knee replacement
October 22, 2018 - Gilead Sciences presents Phase 3 results of filgotinib in biologic-experienced rheumatoid arthritis at 2018 ACR/ARHP Annual Meeting
October 22, 2018 - Study shows potential positive impact of group prenatal care on birth outcomes
October 22, 2018 - Immunotherapy with pembrolizumab extends survival in metastatic or recurrent head and neck cancer
October 22, 2018 - Health Tip: Keep Ticks Away
October 22, 2018 - Obsessive-compulsive disorder – Genetics Home Reference
October 22, 2018 - Researchers find disrupted functional connectivity in cerebellum of adults with HF-ASD
October 22, 2018 - Deciphera presents Phase 1 clinical results of DCC-2618 in patients with gastrointestinal stromal tumors
October 22, 2018 - Combination of Opdivo and Yervoy shows four-year survival benefits in patients with advanced melanoma
October 22, 2018 - Overcoming bottlenecks in early drug discovery with the power of sound
October 22, 2018 - Scientists discover genes that contribute to ADHD development
October 22, 2018 - Incyte announces Phase 2 FIGHT-202 trial data in patients with cholangiocarcinoma
October 22, 2018 - FDA approves update to Rituxan label to include information on treatment of rare forms of vasculitis
October 22, 2018 - At-home biofeedback therapy effective in relieving difficult-to-treat constipation
October 22, 2018 - Merck presents KEYNOTE-057 trial results for patients with high-risk non-muscle invasive bladder cancer
October 22, 2018 - People with periodontal disease less likely to reach healthy blood pressure ranges
October 22, 2018 - Phase III LONSURF study shows progression-free survival in patients with refractory metastatic gastric cancer
October 22, 2018 - Primary care doctors ‘not doing enough’ to curb STDs
October 22, 2018 - Pfizer announces PALOMA-3 trial results in patients with HR+, HER2- metastatic breast cancer
October 22, 2018 - ImmunoGen announces study results of platinum-resistant ovarian cancer therapy at ESMO 2018 Congress
October 22, 2018 - Study findings could set new standard of care for advanced anal cancer
October 22, 2018 - Erlotinib improves progression-free survival in EGFR mutated NSCLC
October 22, 2018 - Pain, insomnia, and depression often drive osteoarthritis patients to seek medical care
October 22, 2018 - The International Society of Refractive Surgery honors Vivior Chairman with Casebeer Award
October 22, 2018 - Multi-strain probiotic helps reduce chemotherapy-induced diarrhea in cancer patients
October 22, 2018 - Study shows potential of avelumab plus axitinib as new treatment option for patients with advanced RCC
October 22, 2018 - Vertex gets European CHMP positive opinion for KALYDECO to treat patients with cystic fibrosis
October 22, 2018 - Phase III trial reports positive results with HDAC inhibitor in advanced breast cancer patients
October 22, 2018 - Prostate radiotherapy improves survival in men with low burden of metastatic disease
October 22, 2018 - Duration of respiratory disturbances may better predict mortality risk from OSA
October 22, 2018 - Free phone app helps low-income obese patients to lose weight
October 22, 2018 - Immunotherapy with nivolumab and ipilimumab may improve survival in patients with MSI-high metastatic colorectal cancers
October 22, 2018 - FOTIVDA expected to be included in new ESMO guidelines for advanced renal cell carcinoma
October 22, 2018 - Compression Collar May Protect Brain of Female Soccer Players
October 22, 2018 - Technique visualizes neuron communication
October 22, 2018 - Advancement in medical imaging methods for health care
October 22, 2018 - Takeda presents vedolizumab phase 3 VISIBLE 1 trial results for treatment of moderately to severely active ulcerative colitis
October 22, 2018 - Immunotherapy increases survival in some patients with metastatic triple negative breast cancer
October 22, 2018 - Exelixis presents CABOSUN and METEOR trial results in patients with advanced renal cell carcinoma
October 22, 2018 - LYNPARZA Phase III SOLO-1 results show improved outcome for patients with advanced BRCA-mutated ovarian cancer
October 22, 2018 - Brainlab unveils ExacTrac Dynamic at ASTRO meeting in San Antonio, Texas
October 22, 2018 - Not exercising is worse than smoking, diabetes or heart disease finds study
October 22, 2018 - Shorter course of trastuzumab could be an option for women with HER2+ early breast cancer
October 22, 2018 - Map of Mouse Hippocampus Could Be Weapon Against Alzheimer’s
October 22, 2018 - Psychotropic polypharmacy is common in Alzheimer’s disease
October 22, 2018 - Texas A&M and UTA establish Texas Genomics Core Alliance
October 22, 2018 - Analyzing mouse’s potential as animal model of decision-making
October 22, 2018 - Radiotherapy can prolong survival in prostate cancer
October 22, 2018 - A genetic mutation involved in relapse
October 21, 2018 - Report reveals growing impact of cannabis on young people
October 21, 2018 - NSF awards $5 million grant to help scientists magnify societal impact of research
October 21, 2018 - Fertility Rates Down for Each Urbanization Level 2007 to 2017
October 21, 2018 - Genetically engineered 3-D human muscle transplant in a murine model
October 21, 2018 - Moms’ tight work schedules may affect their children’s sleep
October 21, 2018 - AHA: No Direct Link Between Preeclampsia and Cognitive Impairment, Study Finds
October 21, 2018 - Weight loss success linked with active self-control regions of the brain
October 21, 2018 - Scripps researchers successfully test potential new smoking-cessation treatment in rodents
October 21, 2018 - More accurate and less stressful way to measure a baby’s heartbeat
October 21, 2018 - Researchers show better cardiorespiratory fitness leads to longer life
October 21, 2018 - Healthy candies for diabetic patients
October 21, 2018 - Environment impact of microplastics remains unclear
October 21, 2018 - Antibiotics for appendicitis? Surgery often not needed
October 21, 2018 - AHA and AMA recognize more than 800 medical practices, health systems for blood pressure control
October 21, 2018 - Scientists obtain clearest ever image of Ebola virus protein
October 21, 2018 - Study reveals connection between two proteins known to be hyperactive in cancer
New drug discovery system allows scientists to target ‘undruggable’ enzymes

New drug discovery system allows scientists to target ‘undruggable’ enzymes

image_pdfDownload PDFimage_print

A new drug discovery system allows scientists to specifically target members of an important family of enzymes, called phosphatases, which were previously considered mostly “undruggable”.

Scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology, in Cambridge, UK, demonstrated the capabilities of the new system by identifying a molecule that could successfully target a phosphatase to reduce the accumulation of Huntington’s disease-associated proteins in the brains of mice.

The findings, published in Cell, could enable scientists to screen for drugs that can target specific phosphatases. Phosphatases are a type of enzyme that are a key part of signaling in cells – turning processes on and off. Most signaling starts with an activation signal – often when a type of enzyme called a kinase attaches a chemical tag, a phosphate group, to specific proteins to change their function. The signal is stopped by phosphatase enzymes, which cut off the phosphate group.

There are more than 200 types of phosphatases involved in many different processes in cells, so any drug must selectively target only the right one, otherwise it will produce serious side-effects or kill the cell.

Many drugs have been developed that can target specific kinases (such as anti-cancer drugs), but developing drugs that can specifically target particular phosphatases has proved difficult – because the functional part that cuts off phosphate groups is common to all phosphatases, so drugging one phosphatase inhibits hundreds of them and kills cells.

Dr Anne Bertolotti from the MRC Laboratory of Molecular Biology, who led the study, said: “For decades, with no way to selectively target phosphatases, research into them has lagged behind kinases and they’ve been described as undruggable. Our new system is only a first step, but we hope cracking this problem will stimulate phosphatase research and drug development.

“Targeting phosphatases – instead of kinases – is like targeting the brake, rather than the accelerator, on signals in cells. By inhibiting a phosphatase, we prolong a signaling event that has already been turned on, which may offer safer ways to specifically alter signaling in cells and help to create new drugs with fewer side-effects.”

The new system builds on previous work by the same scientists in which they created functional synthetic versions of phosphatase proteins.

These synthetic phosphatases are tethered to chips so they can be screened to find a molecule that binds to one type of phosphatase, but to none of the other types. The successful molecule is then tested in cells grown in a dish to check it is safe before beginning testing in mice.

Targeting Huntington’s disease

The researchers used the system to discover a molecule that showed promise in a mouse model of Huntington’s disease.

Many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntingdon’s diseases, feature misfolded proteins that accumulate in cells in the brain. The researchers hoped that slowing down a cell’s production of proteins could leave its ‘quality control machinery’ with more capacity to clear up the misfolded proteins.

In this study, they aimed to slow down the cell’s protein production machinery by targeting a specific phosphatase (designated ‘PPP1R15B’). They used their new drug discovery platform and found a molecule, called Raphin1, that targeted only that phosphatase.

When they tested Raphin1 in a mouse model of Huntington’s disease, they found it could cross into the brain where it reduced the accumulation of the disease-associated misfolded proteins in neurons. The scientists emphasize that this is early stage research and more work is needed to test if the drug will be safe or effective in humans.

Dr Anne Bertolotti said: “Since Huntington’s disease runs in families and can be diagnosed genetically, early diagnosis could provide what we hope is a window of opportunity to target the disease before symptoms appear. Our unique approach manipulates cells to slow down normal functions and give them a chance to clear up the misfolded proteins that are characteristic of Huntington’s. However, it will take some years before we know if this approach works in humans and is safe.”

Source:

https://mrc.ukri.org/news/browse/drugs-to-target-undruggable-enzymes-critical-in-many-diseases/

About author

Related Articles