A5052101341- Computational Drug Discovery Methods
- Ion Channels and Receptors
- Protein purification and stability
- Retinal and Macular Surgery
- Monoclonal and Polyclonal Antibodies Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Essential Oils and Antimicrobial Activity
- Retinal Diseases and Treatments
- Phytochemicals and Antioxidant Activities
- Cancer-related gene regulation
- TGF-β signaling in diseases
- Statistical Methods in Clinical Trials
- Pharmacogenetics and Drug Metabolism
- Pharmaceutical studies and practices
- Cell Adhesion Molecules Research
- Retinal Development and Disorders
Abstract Transforming growth factor β (TGFβ) signaling has been recently shown to reduce antitumor response PD-L1 blockade, leading a renewed enthusiasm in developing anti-TGFβ therapies for potential combination with cancer immunotherapy agents. Inhibition of TGFβ nonclinical toxicology species is associated serious adverse toxicities including cardiac valvulopathies and anemia. Previously, cardiovascular have thought be limited small molecule inhibitors receptor not considered liability...
Abstract The transforming growth factor-β (TGFβ) cytokine family, which comprises three pleiotropic cytokines (TGFβ1, TGFβ2, and TGFβ3), plays a key role in many diseases including cancer fibrosis. of TGFβ disease is well established efforts to develop therapies via inhibition the isoforms their receptors have been pursued for decades. Unfortunately, progress this pursuit has limited as complete signaling pathway using small molecule inhibitors receptor or following administration potent...
Abstract The transforming growth factor-β (TGFβ) cytokine family, which comprises three pleiotropic cytokines (TGFβ1, TGFβ2, and TGFβ3), plays a key role in many diseases including cancer fibrosis. of TGFβ disease is well established efforts to develop therapies via inhibition the isoforms their receptors have been pursued for decades. Unfortunately, progress this pursuit has limited as complete signaling pathway using small molecule inhibitors receptor or following administration potent...
GDC-0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile pharmacodynamic (PD) effects were evaluated in this first-in-human (FIH) study. A starting single dose 25 mg was selected based on integrated preclinical PK, PD, toxicology data following oral administration guinea pigs, rats, dogs, monkeys. Human PK PK-PD characterized...
Long-acting delivery platforms for intravitreal therapies are an active area of research in ophthalmic drug development. The aim these is to decrease the burden patients, by increasing period between injections. This brief communication describes in-life, histologic and immunohistochemical findings associated with repeat-dose administration poly D, L sustained lactide-co-glycolide polymeric rods, depot, cynomolgus monkey ( Macaca fascicularis). These nonclinical investigations illustrate a...
MTBT1466A is a high-affinity TGFβ3-specific humanized IgG1 monoclonal antibody with reduced Fc effector function, currently under investigation in clinical trials as potential anti-fibrotic therapy. Here, we characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of mice monkeys predicted PK/PD humans to guide selection first-in-human (FIH) starting dose. demonstrated typical IgG1-like biphasic PK profile monkeys, human clearance 2.69 mL/day/kg t1/2 20.4 days are consistent those...