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MAO-B, GABRA5 identified as astrocyte targets in subcortical stroke

DISEASE CATEGORY: Neurology INDICATION: Stroke Inhibiting MAO-B or GABRA5 could treat subcortical stroke by restoring regional glucose metabolism and alleviating diaschisis, neurological dormancy at sites distant from a focal brain injury. In a rat model...

Oral small molecule viral RNA polymerase inhibitor for parainfluenza virus

DISEASE CATEGORY: Infectious disease INDICATION: Parainfluenza virus (PIV) An isoquinolylbenzamide-based inhibitor of viral RNA-dependent RNA polymerase could treat infections by PIV and other paramyxoviruses. Cell-based high-throughput screens of 141,936 small molecules yielded an isoquinolylbenzamide-based compound,...

ADORA2B agonism for obesity and aging-induced sarcopenia

DISEASE CATEGORY: Endocrine/metabolic; musculoskeletal INDICATION: Obesity; musculoskeletal Promoting adenosine signaling through ADORA2B could treat obesity and aging-induced sarcopenia. In brown adipose tissue biopsies from lean and overweight individuals, ADORA2B expression was lower in older individuals...

Targeting the metabolic enzyme DGAT1 to treat glioblastoma

DISEASE CATEGORY: Cancer INDICATION: Brain cancer DGAT1 inhibition could treat glioblastoma multiforme (GBM) by promoting fat catabolism. Levels of triglycerides and lipid droplets were higher in postmortem brain tissue from GBM patients than individuals without...

Activating potassium channel KCNJ3 to treat epilepsy

DISEASE CATEGORY: Neurology INDICATION: Epilepsy A thiophenylurea-based activator of the potassium channel KCNJ3 could treat epilepsy. In a mouse model of chemically induced epilepsy, the KCNJ3 activator reduced seizure severity and the duration of tonic...

Vesicular trafficking protein fusion targets for metastatic osteosarcoma

DISEASE CATEGORY: Cancer INDICATION: Bone cancer Interrupting the interaction between RAP1GDS1, which can regulate cell migration, and vesicle trafficking protein RAB22A fusions could treat metastatic osteosarcoma bearing the mutations. The RAB22A fusion proteins are caused...

Antisense-mediated exon skipping for X-linked Alport syndrome

DISEASE CATEGORY: Renal INDICATION: Renal Exon skipping therapy with an antisense oligonucleotide (ASO) targeting a truncating variant in exon 21 of COL4A5 could treat severe X-linked Alport syndrome. The ASO led to complete exon 21...

Fat metabolism enzyme DECR1 as castration-resistant prostate cancer target

DISEASE CATEGORY: Cancer INDICATION: Prostate cancer Inhibiting the β oxidation enzyme DECR1 could treat castration-resistant prostate cancer. In biopsies from prostate cancer patients, DECR1 protein levels were higher after the development of resistance to androgen...

CAPN2 inhibition for concussion-associated neuropathy and behavioral changes

DISEASE CATEGORY: Neurology INDICATION: Neurology Inhibiting the calcium-dependent protease CAPN2 could treat neuropathy and behavioral changes caused by repeated concussions. In a mouse model of traumatic brain injury mediated by controlled cortical impact, excitatory neuron-specific...

Scripps mAb shows signs of COVID-19 protection in hamsters

DISEASE CATEGORY: Infectious disease INDICATION: Coronavirus A team led by Scripps Research Institute researchers has identified an anti-spike mAb that could treat COVID-19. High throughput screening of 2,045 antibodies derived from eight donors, who previously...

Inhibiting proteolytic activation of the receptor PAR2 for eosinophilic esophagitis

DISEASE CATEGORY: Inflammation INDICATION: Eosinophilic esophagitis Inhibiting the extracellular serine protease KLK5 or its substrate PAR2 could treat eosinophilic esophagitis, a food antigen-driven inflammatory disease. Single-cell sequencing revealed aberrant KLK5 expression in multiple cell populations...

Pyrazinediamine-based mitochondrial uncoupler for obesity

DISEASE CATEGORY: Endocrine/metabolic INDICATION: Obesity A mitochondrial protonophore uncoupler could treat obesity. In mouse liver cells, a pyrazinediamine-based tool compound stimulated oxygen consumption rate seven times more potently than the prototype mitochondrial uncoupler 2,4-dinitrophenol (DNP),...

Promoting degradation of the MDM2 oncogene for liposarcoma

DISEASE CATEGORY: Cancer INDICATION: Sarcoma A pyrido-indole-based tool compound that triggers degradation of MDM2, an enzyme that suppresses p53 expression, could treat liposarcoma. In 10 human liposarcoma cell lines, the compound inhibited growth with IC...

AADAC identified as protective factor against diabetic atherosclerosis

DISEASE CATEGORY: Cardiovascular; endocrine/metabolic INDICATION: Atherosclerosis; diabetes Promoting the expression of AADAC, a deacetylase, in vascular smooth muscle cells could treat atherosclerosis in Type II diabetics. Induced pluripotent stem (iPS) cell-derived vascular smooth muscle cells...

Blocking cGAS for colitis

DISEASE CATEGORY: Gastrointestinal INDICATION: Colitis Colitis may be treatable by targeting cGAS, a cytosolic DNA sensor that triggers inflammatory signaling through STING activity. In a mouse model of chemically induced colitis, systemic GSDMD knockout exacerbated...