Discovery of N-(pyridin-4-yl)-1,5-naphthyridin-2-amines as potential tau pathology PET tracers for Alzheimer’s Disease.

Discovery of N-(pyridin-4-yl)-1,5-naphthyridin-2-amines as potential tau pathology PET tracers for Alzheimer’s Disease.

Authors: Rombouts FJR, Andrés JI, Ariza M, Alonso JM, Austin N, Bottelbergs A, Chen L, Chupakhin V, Cleiren E, Fierens K, Fontana A, Langlois X, Leenaerts JE, Mariën J, Martinez Lamenca C, Salter R, Schmidt ME, Te Riele P, Wintmolders C, Trabanco AA, Zhang W, Macdonald GJ, Moechars D
Publication: J Med Chem
Keywords: alzheimer's disease, medicinal chemistry, pharmacokinetic
Software: ADMET Predictor®

A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified...

IMI – oral biopharmaceutics tools project – evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds

IMI – oral biopharmaceutics tools project – evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds

Authors: Margolskee A, Darwich AS, Pepin X, Pathak SM, Bolger MB, Aarons L, Rostami-Hodjegan A, Angstenberger J, Graf F, Laplanche L, Müller T, Carlert S, Daga PR, Murphy D, Tannergren C, Yasin M, Greschat-Schade S, Mück W, Muenster U, van der Mey D, Frank KJ, Lloyd R, Adriaenssen L, Bevernage J, De Zwart L, Swerts D, Tistaert C, Van Den Bergh A, Van Peer A, Bennett J, McAllister M, Wong M, Zane P, Ollier C, Vicat P, Kolhmann M, Marker A, Brun P, Mazuir F, Beilles S, Venczel M, Boulenc X, Loos P, Lennernäs H, Abrahamsson B
Publication: Eur J Pharm Sci
Keywords: absorption biopharmaceutics, drug database, modelling and simulation (M&S), oral bioavailability (F(oral)), physiologically based pharmacokinetics (PBPK)

Predicting oral bioavailability (Foral) is of importance for estimating systemic exposure of orally administered drugs.

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysing In Silico performance across different compound classes

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysing In Silico performance across different compound classes

Authors: Darwich AS, Margolskee A, Pepin X, Aarons L, Galetin A, Rostami-Hodjegan A, Carlert S, Hammarberg M, Hilgendorf C, Johansson P, Karlsson E, Murphy D, Tannergren C, Thörn H, Yasin M, Mazuir F, Nicolas O, Ramusovic S, Xu C, Pathak SM, Korjamo T, Laru J, Malkki J, Pappinen S, Tuunainen J, Dressman J, Hansmann S, Kostewicz ES, He H, Heimbach T, Wu F, Hoft C, Pang Y, Bolger MB, Huehn E, Lukacova V, Mullin JM, Szeto KX, Costales C, Lin J, McAllister M, Modi S, Rotter C, Varma M, Wong M, Mitra A, Bevernage J, Van Peer A, Lloyd R, Shardlow C, Langguth P, Mishenzon I, Nguyen MA, Brown J, Lennernäs H, Abrahamsson B
Publication: Eur J Pharm Sci
Keywords: absorption, biopharmaceutics, drug database, modelling and simulation (M&S), oral bioavailability (F(oral)), Physiologically based pharmacokinetic (PBPK) modeling
Software: GastroPlus®

Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp® Simulator, and GastroPlus™) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools...

Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

Authors: Park MH, Shin SH, Lee GH, Yu B, Shin YG
Publication: Korean J Physiol Pharmacol
Keywords: caffeine, ciprofloxacin, drug-drug interactions (DDIs), physiologically based pharmacokinetics
Software: ADMET Predictor®, GastroPlus®

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction...

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results

Authors: Margolskee A, Darwich AS, Pepin X, Aarons L, Galetin A, Rostami-Hodjegan A, Carlert S, Hammarberg M, Hilgendorf C, Johansson P, Karlsson E, Murphy D, Tannergren C, Thörn H, Yasin M, Mazuir F, Nicolas O, Ramusovic S, Xu C, Pathak SM, Korjamo T, Laru J, Malkki J, Pappinen S, Tuunainen J, Dressman J, Hansmann S, Kostewicz ES, He H, Heimbach T, Wu F, Hoft C, Laplanche L, Pang Y, Bolger MB, Huehn E, Lukacova V, Mullin JM, Costales C, Lin J, McAllister M, Modi S, Rotter C, Varma M, Wong M, Mitra A, Bevernage J, Biewenga J, Van Peer A, Lloyd R, Shardlow C, Langguth P, Mishenzon I, Nguyen MA, Brown J, Lennernäs H, Abrahamsson B
Publication: Eur J Pharm Sci
Keywords: absorption, biopharmaceutics, drug database, modelling and simulation (M&S), oral bioavailability (F(oral)), physiologically based pharmacokinetics (PBPK)
Software: GastroPlus®

Orally administered drugs are subject to a number of barriers impacting bioavailability (Foral), causing challenges during drug and formulation development.

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors.

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors.

Authors: Woodhead JL, Brock WJ, Roth SE, Shoaf SE, Brouwer KL, Church R, Grammatopoulos TN, Stiles L, Siler SQ, Howell BA, Mosedale M, Watkins PB, Shoda LKM
Publication: Toxicol Sci
Keywords: ADPKD, DILI, quantitative systems pharmacology modeling, tolvaptan
Software: DILIsym®
Division: DILIsym Services

Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD).

In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions

In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions

Authors: Mercuri A, Wu S, Stranzinger S, Mohr S, Salar-Behzadi S, Bresciani M, Fröhlich E
Publication: Int J Pharm
Keywords: biorelevant dissolution, permeability, PK modelling, solubility, tacrolimus

This work aims to better understand the in vivo behaviour of modified release (MR) formulations (Envarsus® tablets and Advagraf® capsules) using in vitro properties of tacrolimus and in silico simulations.

Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA’s Office of Pharmaceutical Quality

Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA’s Office of Pharmaceutical Quality

Authors: Fisher AC, Lee SL, Harris DP, Buhse L, Kozlowski S, Yu LJ, Kopcha M, Woodcock J
Publication: Int J Pharm
Keywords: emerging technology, pharmaceutical quality, policy, quality standards, regulatory science
Software: GastroPlus®

Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States.

Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis

Network pharmacology-based identification of key pharmacological pathways of Yin–Huang–Qing–Fei capsule acting on chronic bronchitis

Authors: Yu G, Zhang Y, Ren W, Dong L, Li J, Geng Y, Zhang YF, Defeng L, Xu H, Yang H
Publication: Int J Chron Obstruct Pulmon Dis
Keywords: asthma pathway, chronic bronchitis, network pharmacology, raditional Chinese medicine, Yin–Huang–Qing–Fei capsule
Software: MedChem Studio™

For decades in China, the Yin–Huang–Qing–Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects.

Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)

Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)

Authors: Wang C, Zhao Q, Vargas M, Jones JO, White KL, Shackleford DM, Chen G, Saunders J, Ng AC, Chiu FC, Dong Y, Charman SA, Keiser J, Vennerstrom JL
Publication: J Med Chem
Keywords: antischistosomal, antischistosomal hydantoins, igand-androgen receptor

The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced...

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV): (Part 2 – Hybrid LBA/LCMS and input from regulatory agencies)

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV): (Part 2 – Hybrid LBA/LCMS and input from regulatory agencies)

Authors: Song A, Lee A, Garofolo F, Kaur S, Duggan J, Evans C, Palandra J, Donato LD, Xu K, Bauer R, Bustard M, Chen L, Cocea L, Croft S, Galliccia F, Haidar S, Hughes N, Ishii-Watabe A, Islam R, Jones B, Kadavil J, Krantz C, Santos GML, Olah T, Pedras-Vasconcelos J, Staelens L, Saito Y, Savoie N, Scheibner K, Spitz S, Tampal N, Thomas E, Vinter S, Wakelin-Smith J, Welink J, Zeng J, Zhou S
Publication: Bioanalysis
Keywords: bioanalysis, biomarker assay validation (BAV), biomarkers, immunogenicity, LCMS, Workshop on Recent Issues in Bioanalysis (WRIB)
Division: Simulations Plus

The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide.

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV): (Part 3 – LBA, biomarkers and immunogenicity)

2016 White Paper on recent issues in bioanalysis: focus on biomarker assay validation (BAV): (Part 3 – LBA, biomarkers and immunogenicity)

Authors: Richards S, Amaravadi L, Pillutla R, Birnboeck H, Torri A, Cowan KJ, Papadimitriou A, Garofolo F, Satterwhite C, Piccoli S, Wu B, Krinos-Fiorotti C, Allinson J, Berisha F, Cocea L, Croft S, Fraser S, Galliccia F, Gorovits B, Gupta S, Gupta V, Haidar S, Hottenstein C, Ishii-Watabe A, Jani D, Kadavil J, Kamerud J, Kramer D, Litwin V, Santos GML, Nelson R, Ni Y, Pedras-Vasconcelos J, Qiu Y, Rhyne P, Safavi A, Saito Y, Savoie N, Scheibner K, Schick E, Siguenza PY, Smeraglia J, Staack RF, Subramanyam M, Sumner G, Thway T, Uhlinger D, Ullmann M, Vitaliti A, Welink J, Whiting CC, Xue L, Zeng R
Publication: Bioanalysis
Keywords: bioanalysis, biomarker assay validation (BAV), biomarkers, immunogenicity, LCMS, Workshop on Recent Issues in Bioanalysis (WRIB)
Division: Simulations Plus

The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide.