Sapanisertib (TAK-228) is an investigational, orally available, potent and highly selective mTORC1/2 inhibitor demonstrating promise in numerous malignancies.
Physiologically-Based Pharmacokinetic Modeling in Lead Optimization II: “Rational Bioavailability Design” by Global Sensitivity Analysis to Identify Properties Affecting Bioavailability.
When medicinal chemists need to improve oral bioavailability (%F) during lead optimization, they systematically modify compound properties mainly based on their own experience and general rules of thumb.
Physiologically-Based Pharmacokinetic Modeling in Lead Optimization I: Evaluation and Adaptation of GastroPlus to Predict Bioavailability of Medchem Series
When medicinal chemists need to improve bioavailability (%F) within a chemical series during lead optimization, they synthesize new series members with systematically modified properties...
Preparation and Evaluation of Progesterone Nanocrystals to Decrease Muscle Irritation and Improve Bioavailability.
Progesterone (PG) is a crucial immunomodulatory agent during early pregnancy, and nowadays PG oil-based injection (PG/OI) has a huge market all over the world.
Model-informed drug development for malaria therapeutics
Malaria is a critical public health problem resulting in substantial morbidity and mortality, particularly in developing countries. Owing to the development of resistance toward current therapies, novel approaches to accelerate...
Developing a mechanistic absorption model to predict the pharmacokinetics of immediate-release weak base drugs with a long Tmax by incorporating lysosomal trapping.
The objectives of this study were 1) to develop and verify mechanistic absorption models to predict the pharmacokinetics (PK) of two immediate-release weak base drug (WBD) products (Drug X and Drug Y) with a...
In Vitro Dissolution Methodology And Estimated Consequences Of Biowaiver Extension For Immediate Release Solid Oral Dosage Forms With Metformin Hydrochloride
The in vitro dissolution methodologies are frequently used as quality control tools for the assessment of solid oral dosage forms.
Every Jack has His Jill: Finding a Target for Your Combinatorial Library
Pharmaceutical companies regularly run campaigns to evolve their proprietary chemical libraries which are among their most valuable assets.
Physiologically Based Oral Absorption Modelling to Study Gut-Level Drug Interactions
Physiologically based oral absorption models are in silico tools primarily used to guide formulation development and project the clinical performance of formulation variants.
The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs, Ketoconazole and Raloxifene
The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the...
Synaptophysin expression on circulating tumor cells in patients with castration resistant prostate cancer undergoing treatment with abiraterone acetate or enzalutamide
Background: With the advent of secondary androgen receptor (AR)-targeted therapies in metastatic castration resistant prostate cancer (PC), nonadenocarcinoma PCs are...
Identification of mechanisms of resistance to treatment with abiraterone acetate or enzalutamide in patients with castration-resistant prostate cancer (CRPC)
Background: Two androgen receptor (AR)-targeted therapies, enzalutamide and abiraterone acetate plus prednisone (abiraterone), have been approved for the treatment...
Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and Serum Biomarkers to Cimaglermin Alfa (GGF2) Clinical Trials
Cimaglermin alfa (GGF2) is a recombinant human protein growth factor in development for heart failure.
Software based approaches for drug designing and development: A systematic review on commonly used software and its applications.
Drug discovery include drug designing and development, is a multifarious and expensive endeavor, where least number of drugs that pass the clinical trials makes it to market.
Phase 1 and pharmacokinetic study of LY3007113, a p38 MAPK inhibitor, in patients with advanced cancer
Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion.
Modeling of prolactin response following dopamine D2 receptor antagonists in rats: can it be translated to clinical dosing?
Prolactin release is a side effect of antipsychotic therapy with dopamine antagonists, observed in rats as well as humans.
A cross-species translational pharmacokinetic-pharmacodynamic evaluation of core bodytemperature reduction by the TRPM8 blocker PF-05105679.
PF-05105679 is a moderately potent TRPM8 blocker which has been evaluated for the treatment of cold pain sensitivity.
Ribociclib Bioavailability Is Not Affected by Gastric pH Changes or Food Intake: In Silico and Clinical Evaluations.
Ribociclib (KISQALI®), a cyclin-dependent kinase 4/6 inhibitor approved for the first-line treatment of HR+/HER2– advanced breast cancer with an aromatase inhibitor, is administered with...
Intrinsic dissolution simulation of highly and poorly soluble drugs for BCS solubility classification
Intrinsic dissolution testing allows characterizing drug substances through its dissolution rate when exposed to a specified surface area in a specific dissolution media.