A5089720680- Cancer-related Molecular Pathways
- RNA regulation and disease
- Viral Infections and Immunology Research
- Click Chemistry and Applications
- Estrogen and related hormone effects
- Cancer Research and Treatments
- Crime, Illicit Activities, and Governance
- Genomic variations and chromosomal abnormalities
- Irish and British Studies
- DNA and Nucleic Acid Chemistry
- Advanced Breast Cancer Therapies
- Metastasis and carcinoma case studies
- Multiple Sclerosis Research Studies
- Acute Lymphoblastic Leukemia research
- Cytokine Signaling Pathways and Interactions
- Autoimmune and Inflammatory Disorders Research
- Immune Cell Function and Interaction
- HIV, Drug Use, Sexual Risk
- Nanoparticle-Based Drug Delivery
- Opioid Use Disorder Treatment
- Peptidase Inhibition and Analysis
- Folate and B Vitamins Research
- Veterinary Oncology Research
- Cancer therapeutics and mechanisms
Endocyte (United States)
2013-2021
Novartis (United States)
2021
Activated macrophages in the experimental model of multiple sclerosis (MS) express folate receptor-β (FR-β), representing a promising target for treatment MS. Here, we both evaluated efficacy novel folate-aminopterin construct (EC2319) rat focal and investigated utility 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated (68Ga-FOL) assessing inflammatory lesions. In addition, whether FR-β is expressed brain patients with MS.Focal delayed-type hypersensitivity autoimmune...
Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRβ), with subnanomolar affinity for vitamin folic acid (FA), is upregulated during immune in hematopoietic cells of myeloid lineage. This phenomenon has inspired a strong interest exploring FRβ-directed diagnostics/therapeutics. Previously, we have reported that FA-targeted...
The purpose was to determine the safety and antitumor activity of a folate-tubulysin conjugate (EC0531) in relevant preclinical animal model, dogs with naturally-occurring invasive urothelial carcinoma (iUC). Canine iUC is an aggressive cancer high folate receptor (FR) expression similar that certain forms human cancer.A 3+3 dose escalation study EC0531 (starting 0.2 mg/kg given intravenously at two-week intervals) performed expressing levels FRs (>50% positive tumor cells). Pharmacokinetic...
Abstract Folate receptor (FR)-targeted small molecule drug conjugates (SMDCs) have shown promising results in early stage clinical trials with microtubule destabilizing agents, such as vintafolide and EC1456. In our effort to develop FR-targeted SMDCs varying mechanisms of action, we synthesized EC2629, a folate conjugate DNA crosslinking agent based on novel DNA-alkylating moiety. This was found be extremely potent an vitro IC50 ~ 100× lower than constructed various inhibitors. EC2629...
Abstract Several folate-targeted small-molecule drug conjugates (SMDCs) are under development for the treatment of folate receptor-positive (FR+) cancer. To date, all clinical SMDCs have been constructed with a disulfide-based linker strategically placed in between targeting ligand (e.g. folate) and therapeutically active drug. At least SMDCs, disulfide remains relatively stable circulation, but it rapidly breaks once SMDC enters reductive endocytic process within targeted cell. While this...
Abstract Triple negative breast cancer (TNBC) patients are insensitive to hormonal or anti-HER2 therapy and have a higher recurrence rate among all subtypes. There is lack of common therapeutic targets in TNBC due its six distinct molecular characteristics. Recently, ~50% cases were found express the folate receptor alpha (FRα) on tumor cells. FRα GPI-anchored membrane glycoprotein capable bringing folate-targeted small-molecule drug conjugates (SMDCs) inside cell. EC1456 folic...