Age impacts disease tolerance to sepsis, study shows
The immune system is a critical factor of host survival, allowing resistance to infections and maintaining tissue integrity. The activation of immune responses requires precise regulation to assure a balance between the benefits and costs of these responses. Moreover, the theory of antagonistic pleiotropy proposes that traits beneficial to early-life fitness may sustain costs that manifest later in life, after the period of strongest natural selection, where aging introduces further complexities for cooperative defenses. As a result of this, hosts of different ages may manifest distinct disease courses despite infection with the same pathogen.

Age impacts disease tolerance to sepsis, study shows
The immune system is a critical factor of host survival, allowing resistance to infections and maintaining tissue integrity. The activation of immune responses requires precise regulation to assure a balance between the benefits and costs of these responses. Moreover, the theory of antagonistic pleiotropy proposes that traits beneficial to early-life fitness may sustain costs that manifest later in life, after the period of strongest natural selection, where aging introduces further complexities for cooperative defenses. As a result of this, hosts of different ages may manifest distinct disease courses despite infection with the same pathogen.
Alveus Therapeutics’ ALV-100 gains IND clearance for obesity
Alveus Therapeutics Inc. has obtained IND clearance from the FDA for ALV-100, for chronic weight management, enabling initiation of a phase Ib study. Dosing has now commenced in the study.
PGC-1α gene delivery protects against kidney reperfusion injury
Renal ischemia-reperfusion injury (IRI) is a type of acute kidney injury commonly affecting hospitalized patients and associated with poor outcomes, including increased risk of death in severe cases. IRI is caused by a transient reduction in renal blood flow followed by blood reperfusion.
Oncolytic measles virus shows activity in pediatric leukemia
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common pediatric cancer. Although pediatric ALL is cured in over 90% of cases, children with high-risk BCP-ALL present increased chance of treatment failure and relapse.
Centre Hospitalier Regional Universitaire de Lille divulges new 3CLpro inhibitors
Centre Hospitalier Regional Universitaire de Lille has patented new 3C-like proteinase (3CLpro; Mpro; nsp5) (SARS-CoV-2; COVID-19 virus) inhibitors reported to be useful for the treatment of SARS-CoV-2 infection (COVID-19).
MicroRNAs in circulating extracellular vesicles as IPF biomarkers
MicroRNAs (miRNAs) are small noncoding RNAs gaining increasing attention due to their crucial role in gene expression regulation and influence in various cellular processes and diseases. miRNAs can be encapsulated in extracellular vesicles (EVs), which are released by most cell types to modulate gene expression in recipient cells.
Pyrimidine-based KRAS inhibitors are structurally novel chemotype
Researchers from Lanzhou University and Southern Medical University (China) have presented the discovery of a structurally distinct pyrimidine-based chemotype for the inhibition of KRAS G12C.
Researchers develop 3,3-dimethyl-2-oxoindiline STING inhibitors
Hyperactivity of the transmembrane adaptor protein STING, which normally helps the cell respond to infection and injury, has been implicated in several autoimmune or inflammatory diseases, including systemic lupus erythematosus and amyotrophic lateral sclerosis.

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Conferences

5-HT2R allosteric ligands attenuate cocaine use and seeking behavior
Substance use and poisoning
Serotonergic G-protein-coupled receptors (GPCRs), including the 5-HT2A receptor (5-HT2AR) and 5-HT2CR, are key regulators of cortical signaling pathways and promising targets for neurotherapeutic drug discovery. Researchers from the University of Texas System have developed AB-0124, a 5-HT2AR...
First-in-class ADC targeting DEM-TXX shows high preclinical efficacy
American Society of Clinical Oncology
Researchers at DEM Biopharma Inc. reported preclinical findings demonstrating the efficacy of DEM-301, a bifunctional antibody-drug conjugate (ADC) engineered to selectively recognize and eliminate tumor cells that express DEM-TXX.
Centessa’s CNT-9982 shows promise for MDD
New compound
Orexin OX2 receptor agonists have demonstrated the ability to enhance wakefulness in rodent models, as well as in nonhuman primates and patients with narcolepsy and idiopathic hypersomnia. Based on recent findings, it has been hypothesized that they may also regulate cognition, mood and other...
Sumitomo’s DSP-3456 exerts antidepressant-like effects
Neurology/psychiatric
About one-third of patients with major depressive disorder (MDD) are treatment resistant. Ketamine is very effective in treatment-resistant depression, but it is associated with psychotomimetic effects. Metabotropic glutamate mGlu2 and mGlu3 receptors negatively regulate the release of glutamate...

Cancer

Avacta’s AVA-6103 gains IND clearance for solid tumors
Regulatory
Avacta Therapeutics (Avacta Group plc) has obtained IND clearance from the FDA for FAP-Exd (AVA-6103), a Precision peptide-drug conjugate based on exatecan.

Infection

NIK inhibitor shows potential for IBD and sepsis
Gastrointestinal
NF-κB-inducing kinase (NIK), also known as MAP3K14, is the key kinase driving noncanonical NF-κB signaling and p100 processing. Researchers from China Pharmaceutical University reported the discovery and preclinical evaluation of a novel NIK inhibitor.

MK-7762 overcomes linezolid limitations in tuberculosis treatment
Researchers from Merck & Co. reported the development of MK-7762, a novel oxazolidine with antitubercular activity designed to overcome the off-target effects of linezolid.
Dual-targeting lipopeptides inhibit SPase I, disrupt membranes in MDR pathogens
Multidrug-resistant (MDR) gram-positive bacteria can evade last-line therapies, such as vancomycin, daptomycin and linezolid, through the development of sophisticated resistance mechanisms that include inactivation of target enzymes, mutations in binding sites, alterations in membrane permeability...

Neurology/psychiatric

Nippon Zoki Pharmaceutical synthesizes new GABA-A receptor subunit positive allosteric modulators
Nippon Zoki Pharmaceutical Co. Ltd. has discovered alkyne derivatives acting as GABA-A receptor subunit α1β2γ2 positive allosteric modulators. As such, they are believed to be useful for the treatment of sleep disorders.
Insilico Medicine and Hygtia partner on ISM-8969
Deals and M&A
Insilico Medicine Cayman Topco and Hygtia Therapeutics Co. Ltd. have entered into an exclusive license and co-development collaboration to advance ISM-8969 worldwide. ISM-8969 is an orally available, brain penetrant NLRP3 inhibitor for CNS disorders.
Sundance Biosciences patents new TYK2 inhibitors for multiple sclerosis
Patents
Sundance Biosciences Inc. has discovered non-receptor tyrosine-protein kinase TYK2 inhibitors potentially useful for the treatment of multiple sclerosis.
Succinate prodrug NV-354 protects the brain in complex I deficiency
Genetic/congenital
Leigh syndrome is a fatal pediatric neurodegenerative disorder caused by mitochondrial dysfunction, most often due to defects in the mitochondrial respiratory chain. The Ndufs4 knockout (Ndufs4 KO) mouse is an established model of the disease, as loss of the NDUFS4 subunit leads to complex I (CI)...
Zincure synthesizes new MMP-9 inhibitors
Patents
Zincure Corp. has discovered matrix metalloproteinase-9 (MMP-9, gelatinase B) inhibitors reported to be useful for the treatment of epilepsy, stroke, multiple sclerosis, hypoglycemic encephalopathy and traumatic brain injury.

Endocrine/metabolic

Scribe eyes clinic with STX-1150 for hypercholesterolemia
Cardiovascular
Scribe Therapeutics Inc. is aiming to advance STX-1150, its lead product candidate for the treatment of hypercholesterolemia, into the clinic around the middle of this year. Hypercholesterolemia is a major driver of atherosclerotic cardiovascular disease.

Biomarkers

Brain-derived tau in blood predicts stroke severity and outcome
Cardiovascular
Brain-derived tau, a protein that is exclusive to the brain and detectable in the blood, could serve as an indicator of brain damage after an ischemic stroke. The analysis of this special form of tau has revealed a relationship between high levels of the protein and extensive brain injury, a higher...

Biallelic variants in COX18 identified as cause of Charcot-Marie-Tooth disease
Genetic/congenital
Charcot-Marie-Tooth (CMT) disease is a group of clinically and genetically heterogeneous sensorimotor peripheral neuropathies. It is the most frequent inherited neuromuscular disorder affecting 9.7-82.3 patients per 100,000 individuals. Over 100 genes with all patterns of inheritance have been...
Neurotrimin unveiled as marker in intellectual disability
Genetic/congenital
Neurotrimin (NTM) is a member of the IgLON family, the disruption of which has been tied to emotional learning deficits and anxiety-like behavior in animal models. A mutation in the NTM gene was found to disrupt NTM protein heterodimerization with other IgLON family members, suggesting a potential...

Gastrointestinal

RIPK1 arises as target in primary sclerosing cholangitis
Inflammatory
Increasing evidence exists regarding receptor-interacting protein kinase 1 (RIPK1), a necroptosis regulator, being involved in inflammation and fibrosis in chronic liver disorders. The relationship between necroptosis and the inhibition of RIPK1...
Nanjing Chia Tai Tianqing Pharmaceutical identifies new somatostatin SST2 receptor agonists
Patents
Nanjing Chia Tai Tianqing Pharmaceutical Co. Ltd. has discovered somatostatin SST2 receptor agonists described as potentially useful for the treatment of acute pancreatitis and peptic ulcer bleeding.
First circRNA-based protein replacement therapy for liver fibrosis
Researchers from Shanghai Institute of Nutrition and Health and Guangming Advanced Research Institute (China) proposed a new strategy based on a circular RNA (circRNA) encoding human relaxin-2 (cRLN2). circRNAs, thanks to their high stability and...
SLIT2 shows promise as a druggable target in liver injury
About 10% of acute hepatitis cases and 50% of acute liver failure are caused by drug induction, where treatment remains largely limited. The SLIT/ROBO signaling axis is composed of the secretory SLIT proteins (SLIT1, SLIT2 and SLIT3) and their...
Fat tissue subtyping gives functional insights
Science
Once it was considered to be more or less a passive energy-storing device that could double as a cushion. But increasingly, fat is conceptualized as an endocrine organ as much as a tissue type. Now, separate research groups have reported new...
Refining, like reducing and replacing, can improve animal research
Drug design, drug delivery and technologies
The concept of the 3 Rs – reducing, refining and replacing animal research – has been championed since the 1950s, when William Russel and Rex Burch argued in their book “The Principles of Humane Experimental Technique” that the 3 Rs could...

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