vidofludimus

Vidofludimus (SC12267) (4SC-101, SC12267) is a novel small molecule inhibitor of dihydroorotate dehydrogenase (DHODH).

Vidofludimus hemicalcium (4sc-101; SC12267) is an orally active compound that acts as a dihydroorotate dehydrogenase (DHODH) inhibitor and serves as a novel modulator of the farnesoid X receptor (FXR). This immunomodulatory agent is utilized in the research of autoimmune disorders, including inflammatory bowel disease (IBD), and is explored for its potential in fatty liver disease research through FXR targeting.

Zotiraciclib, also known as TG02 and SB1317, is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. Zotiraciclib may be useful for the treatment of cancer that crosses the blood brain barrier and acts by depleting Myc through the inhibition of cyclin-dependent kinase 9 (CDK9). It is one of a number of CDK inhibitors under investigation; others targeting CDK9 for the treatment of acute myeloid leukemia include alvocidib and atuveciclib. Myc overexpression is a known factor in many cancers, with 80 percent of glioblastomas characterized by this property.

NR4A agonist-2, derived from the design of Vidofludimus, is a selective pan-NR4A agonist with a dissociation constant (Kd) of 0.10 μM for NR4A1 and half-maximal effective concentrations (EC50) of 0.098 μM, 0.092 μM, and 0.09 μM for Nur77, Nurr1, and NOR-1, respectively. It exhibits 47-fold selectivity for DHODH and demonstrates no cytotoxic activity at concentrations up to 10 μM. NR4A agonist-2 acts by binding to a specific surface pocket in the ligand-binding domain of Nurr1, inhibiting Nurr1 homodimer formation and activating response elements such as NBRE, NurRE, and DR5, thus robustly inducing the expression of neuroprotective genes like BDNF and SOD2. This compound holds potential for research in neurodegenerative diseases including Parkinson's disease, dementia, and multiple sclerosis.