Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics: strategy and approach during the drug discovery phase with four case …

Y Chen, JY Jin, S Mukadam, V Malhi… - … & drug disposition, 2012 - Wiley Online Library
Prospective simulations of human pharmacokinetic (PK) parameters and plasma
concentration–time curves using in vitro in vivo extrapolation (IVIVE) and physiologically based …

Prediction of drug-drug interactions arising from CYP3A induction using a physiologically based dynamic model

LM Almond, S Mukadam, I Gardner, K Okialda… - Drug Metabolism and …, 2016 - ASPET
Using physiologically based pharmacokinetic modeling, we predicted the magnitude of drug-drug
interactions (DDIs) for studies with rifampicin and seven CYP3A4 probe substrates …

Drug–Drug Interaction Potential of Marketed Oncology Drugs: In Vitro Assessment of Time-Dependent Cytochrome P450 Inhibition, Reactive Metabolite Formation …

JR Kenny, S Mukadam, C Zhang, S Tay… - Pharmaceutical …, 2012 - Springer
Purpose To evaluate 26 marketed oncology drugs for time-dependent inhibition (TDI) of
cytochrome P450 (CYP) enzymes. Evaluate TDI-positive drugs for potential to generate reactive …

Discovery of novel PI3-kinase δ specific inhibitors for the treatment of rheumatoid arthritis: taming CYP3A4 time-dependent inhibition

…, MC Lucas, C Lewis, S Mukadam… - Journal of medicinal …, 2012 - ACS Publications
PI3Kδ is a lipid kinase and a member of a larger family of enzymes, PI3K class IA(α, β, δ)
and IB (γ), which catalyze the phosphorylation of PIP2 to PIP3. PI3Kδ is mainly expressed in …

Physiologically based pharmacokinetic modeling as a tool to predict drug interactions for antibody-drug conjugates

Y Chen, D Samineni, S Mukadam, H Wong… - Clinical …, 2015 - Springer
Background and Objectives Monomethyl auristatin E (MMAE, a cytotoxic agent), upon releasing
from valine-citrulline-MMAE (vc-MMAE) antibody-drug conjugates (ADCs), is expected …

Discovery and biological profiling of potent and selective mTOR inhibitor GDC-0349

…, L Bao, U Vijapurkar, S Mukadam… - ACS medicinal …, 2013 - ACS Publications
Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human
tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic …

Discovery of potent and efficacious urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with reduced CYP2C9 inhibition properties

…, X Liang, BM Liederer, J Lin, S Mukadam… - Bioorganic & medicinal …, 2013 - Elsevier
Potent, reversible inhibition of the cytochrome P450 CYP2C9 isoform was observed in a
series of urea-containing nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. This …

Potent Non-Benzoquinone Ansamycin Heat Shock Protein 90 Inhibitors from Genetic Engineering of Streptomyces hygroscopicus

…, CD Reeves, C Carreras, S Mukadam… - Journal of medicinal …, 2009 - ACS Publications
Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy.
We describe the preparation of potent non-benzoquinone ansamycins. One of these …

In vitro and in vivo characterization of CYP inhibition by 1‐aminobenzotriazole in rats

…, A Jaochico, J Ly, Q Ho, S Mukadam… - … & drug disposition, 2016 - Wiley Online Library
Aminobenzotriazole (ABT) is a non‐isoform specific, time‐dependent inhibitor of cytochrome
P450 (CYP) enzymes used extensively in preclinical studies to determine the relative …

[HTML][HTML] BB-301: a silence and replace AAV-based vector for the treatment of oculopharyngeal muscular dystrophy

…, N Lu-Nguyen, K Takahashi, S Mukadam… - … Therapy-Nucleic Acids, 2021 - cell.com
Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant disease that
results from an alanine expansion in the N-terminal domain of Poly-A Binding Protein Nuclear-…