PROTAC Targeted Degradation of IRAK-4 as Potential Treatment in Cancer.

Toll-like receptors and interleukin-1 receptor directly interact with intracellular interleukin receptor associated kinase (IRAK) family members to initiate innate immune and inflammatory responses following activation by pathogens. The IRAK family members are involved in linking the innate immune response to the pathogenesis of various diseases, including cancers, non-infectious immune disorders, and metabolic disorders. The Patent Highlight showcases exemplary PROTAC compounds that exhibit a broad range of pharmacological activities associated with degradation of protein targets for the treatment of cancer.

Targeting the "Undruggable" Driver Protein, KRAS, as Potential Therapy in Prostate Cancer.

In spite of the progress made in the development of KRAS inhibitors, there is still continued interest to develop inhibitors of other KRAS such as KRAS for the treatment of diseases, including prostate cancer, colorectal cancer, and non-small-cell lung cancer. This Patent Highlight provides exemplary compounds having activity as inhibitors of G12D mutant KRAS protein.

Orally Active Forms of DMT, 5-MeO-DMT, and Long-Acting MDMA for the Treatment of Neuropsychiatric Disorders.

This Patent Highlight describes derivatives of DMT, 5-MeO-DMT, and MDMA that are metabolically converted to biologically active analogs. When these prodrugs are administered to a subject, they potentially could be used therapeutically in conditions associated with neurological diseases. Furthermore, the disclosure provides methods to potentially treat conditions comprising major depressive disorder, post-traumatic stress disorder, Alzheimer's disease, Parkinson's disease, schizophrenia, frontotemporal dementia, Parkinson's dementia, dementia, Lewy body dementia, multiple system atrophy, or substance abuse.

Discovery of Potent Deuterated Compounds as Potential KRAS Inhibitors in Cancer Therapy.

The disclosure in this Patent Highlight describes a new class of deuterated compounds that bind directly to KRAS and block its activity. These exemplary deuterated compounds are potentially useful as pharmaceuticals that may possess desirable properties, including bioavailability, stability, and therapeutic index. This may have significant influence in drugs absorption, distribution, metabolism, excretion, and half-life when administered to a human or animal.

5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice.

Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase clinical studies.

Discovery of Selective Aldehyde Dehydrogenase Inhibitors for the Treatment of Cancer.

ALDH1A3 is an important member of 19 aldehyde dehydrogenases, which metabolize reactive aldehydes to their corresponding carboxylic acids, detoxify endogenous and exogenous aldehydes, and are also involved in the biosynthesis of retinoic acid. In addition, ALDH1A3 plays important physiological and toxicological roles in different pathologies, including type II diabetes, obesity, cancer, pulmonary arterial hypertension, and neointimal hyperplasia. Consequently, inhibition of ALDH1A3 may offer new therapeutic options for patients with cancer, obesity, diabetes, and cardiovascular disorder.

Psychedelic-Assisted Neuroplasticity for the Treatment of Mental Health Disorders.

The renaissance of research into psychedelics class of drugs has renewed interest for a possible psychedelic clinical therapy for treating psychiatric conditions such as treatment-resistant depression, major depressive-disorder, post-traumatic stress disorder, and other neuropsychiatric diseases. Psychedelics are known to stimulate neurogenesis and gliogenesis, reduce inflammation, and ameliorate oxidative stress, which makes them promising candidates for therapeutics in psychiatric, neurodegenerative, and movement disorders. The patent highlight showcase methods for treating mental health disorders and promoting neural plasticity.

Discovery of Potent PROTACs for the Potential Treatment of Leukemia.

Janus kinases family PROTACs have been developed that recruit inhibitor of apoptosis protein leading to proteasomal degradation. JAK2 is involved in multiple cytokine pathways, including IL-6-mediated signaling and associated granulocyte-macrophage colony-stimulating factor, which are critical for different physiological processes like hematopoiesis, bone metabolism, and differentiation of B-cells.

Potential Therapeutic Transdermal Psychoactive Drug Delivery Technology.

There is a high rise in depression sufferers worldwide, which has necessitated the need for diverse drug delivery systems that would include conventional and emerging transdermal delivery strategies. A number of approaches have been investigated, including a pro-drug approach, formulation of transdermal patches, micro emulsification, and chemical and physical enhancing technologies.

Emerging Proteolysis Targeting Antibodies (PROTABs) for Application in Cancer Therapy.

The emerging proteolysis targeting antibodies (PROTABs) offer an attractive technology that circumvents some of the challenges of small-molecule intracellular degraders with limited bioavailability and cell permeability. PROTABs present an improved approach to target degradation of membrane-bound and cell surface proteins and use multispecific binding proteins such as multispecific antibodies that bind to at least one transmembrane E3 ubiquitin ligase as well as cell surface proteins intended for degradation.

Potent PROTACs Targeting EGFR Mutants in Drug Discovery.

Epidermal growth factor receptor (EGFR) upregulations are found in many types of cancers, including breast cancer, cholangiocarcinoma, ovarian cancer, prostate cancer, leukemia, and colon cancer. This Patent Highlight showcases PROTAC compounds formed by conjugating EGFR inhibitor with E3 ligase ligand, which recruit targeted proteins to E3 ubiquitin ligase for EGFR mutant protein degradation.

Structure-Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice.

4-Phosphoryloxy-,-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-,-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing mushrooms, including the secondary amine 4-phosphoryloxy--methyltryptamine (baeocystin) and the quaternary ammonium 4-phosphoryloxy-,,-trimethyltryptamine (aeruginascin), but these compounds are not well studied.

Recent Discovery of PARP7 Inhibitors as Anticancer Agents.

The 5-year survival rate for advanced ovarian cancer remains less than 30% and has not improved in recent years. Disclosures in this patent highlight provides PARP7 inhibitors and methods for treating cancers such as ovarian cancer and pancreatic cancers.

Potential Treatment for Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) affects approximately 2% of the population worldwide and is also prevalent in other neuropsychiatric disorders. Serotonin reuptake inhibitors have limited widespread success. Alternate treatment options for OCD and other indications are highlighted using 3-bromo-lysergic acid diethylamide.

Targeted Degradation of Androgen Receptor for the Potential Treatment of Prostate Cancer.

Prostate cancer (PCa) is the fourth most commonly diagnosed cancer in the world. Antiandrogens treatments have eventually mostly induced resistant mutations in patients, and when higher dosages are administered, they might cause adverse effects, such as fatigue, back pain, and constipation. The present Patent Highlight provides PROTACs that degrade or inhibit the androgen receptor at low concentrations in a subject in need of treatment.

MDMA and Their Analogs as Therapeutics for Mental Disorder and Response Predictor.

Provided herein are MDMA and their analogs for the potential psychotherapy-assisted treatment of alcohol use disorder (AUD), post-traumatic stress disorder (PTSD), and a method of predicting dosing and patient response.

ALK Inhibitors for Treating Cancer, Blood, and Kidney Diseases.

Cancers that traditionally have been resistant to apoptosis via chemical- or radiation-based therapies may respond when the treatments are combined with ALK-5 inhibition. Disclosures in this Patent Highlight provide inhibitors of activin-receptor-like kinases such as ALK-5, compositions and methods for increasing red blood cell or hemoglobin levels, and activin antagonists to treat, prevent, or reduce the progression rate or severity of kidney disease.

Selective Cyclin-Dependent Kinase Inhibitors and Their Application in Cancer Therapy.

Every cell cycle step is a well-regulated process controlled by cyclin-dependent kinases (CDKs). Selectivity to individual CDKs is crucial in minimizing potential off target complications. Disclosures in this Patent Highlight provides CDK2-selective inhibitor compounds and methods for treating cancers.

The crystal structure of baeocystin.

The title compound, baeocystin or 4-phosphor-yloxy--methyl-tryptamine {systematic name: 3-[2-(methylazaniumyl)ethyl]-1-indol-4-yl hydrogen phosphate}, CHNOP, has a single zwitterionic mol-ecule in the asymmetric unit. The mol-ecule has an intra-molecular N-H⋯O hydrogen bond between the ammonium cation and the hydro-phosphate anion. In the crystal, the mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds into a three-dimensional network.