A5114803342- Drug Transport and Resistance Mechanisms
- Drug Solubulity and Delivery Systems
- Immune Response and Inflammation
- Pharmacological Effects and Toxicity Studies
- NF-κB Signaling Pathways
- Cancer therapeutics and mechanisms
- Multiple Myeloma Research and Treatments
- Eicosanoids and Hypertension Pharmacology
- Chronic Lymphocytic Leukemia Research
- Analytical Methods in Pharmaceuticals
- Bioactive Compounds and Antitumor Agents
- Cardiac electrophysiology and arrhythmias
- Analytical Chemistry and Chromatography
- Chronic Myeloid Leukemia Treatments
- Protein Degradation and Inhibitors
- Pharmacogenetics and Drug Metabolism
- HIV/AIDS drug development and treatment
- Pharmaceutical studies and practices
- Receptor Mechanisms and Signaling
- Quinazolinone synthesis and applications
- interferon and immune responses
- Ion channel regulation and function
Bristol-Myers Squibb (United States)
2017-2025
Biocon (India)
2015-2018
Bristol-Myers Squibb (India)
2015-2018
Syngene International (India)
2015-2018
The serine/threonine kinase IL-1R-associated (IRAK)4 is a critical regulator of innate immunity. We have identified BMS-986126, potent, highly selective inhibitor IRAK4 activity that demonstrates equipotent against multiple MyD88-dependent responses both in vitro and vivo. BMS-986126 failed to inhibit assays downstream MyD88-independent receptors, including the TNF receptor TLR3. Very little was seen TLR4, which can also activate an pathway. In mice, compound inhibited cytokine production...
Self-emulsifying drug delivery systems (SEDDS) have been used to solubilize poorly water-soluble drugs improve exposure in high-dose pharmacokinetic (PK) and toxicokinetic (TK) studies. However, the absorbable dose is often limited by solubility lipidic SEDDS vehicle. This study focuses on increasing loading of ionizable vehicles using lipophilic counterions prepare salts drugs. formulations two salts-atazanavir-2-naphthalene sulfonic acid (ATV-2-NSA) atazanavir-dioctyl sulfosuccinic...
Abstract Iberdomide is a BCS III CELMoD™ agent currently under development for treatment of multiple myeloma. Five formulations were used during clinical development, starting with active ingredient in gelatin capsule (AIC), followed by subsequent (F1), HPMC capsules (F2 and F3), finally the intended commercial form (ICF). A food effect study Phase I AIC formulation showed no two relative bioavailability studies bridging from to F1 F2 similar systemic exposure. Modeling simulation, based on...
We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent IKur current blocker with selectivity versus hERG, Na and Ca channels, an acceptable preclinical PK profile. Upon further characterization in vivo, compound demonstrated unacceptable level of brain penetration. In effort to reduce the penetration while maintaining overall profile, SAR was developed at C2' position for series close analogues by employing hydrogen bond donors. As...
The study presented here identified and utilized a panel of solubility enhancing excipients to enable the generation flux data in Human colon carcinoma (Caco-2) system for compounds with poor solubility. Solubility Dimethyl acetamide (DMA) 1 % v/v, polyethylene glycol (PEG) 400 1% povidone w/v, poloxamer 188 2.5% w/v bovine serum albumin (BSA) 4% did not compromise Caco-2 monolayer integrity as assessed by trans-epithelial resistance measurement (TEER) Lucifer yellow (LY) permeation....
IRAK4 is an attractive therapeutic target for the treatment of inflammatory conditions. Structure guided optimization a nicotinamide series inhibitors has been expanded to explore front pocket. This resulted in identification compounds such as 12 with improved potency and selectivity. Additionally demonstrated activity pharmacokinetics/pharmacodynamics (PK/PD) model. Further efforts led highly kinome selective 21, which robust PD effect efficacy TLR7 driven model murine psoriasis.
1-Aminobenzotriazole (ABT) is a mechanism-based inactivator of major cytochrome P450 (CYP) enzymes, which used in multiple mechanistic studies. The purpose was to evaluate the effect 2 and 16-h pretreatment regimens ABT on exposures triazolam rat. Another objective gastric emptying acetaminophen. Plasma area under curve (AUC) increased by 101-fold 81-fold for rats pretreated with at 16 h, respectively, compared control rats. Time reach maximum concentration 0.3, 4.8 3.7 h control, animals,...