- Suppliers
ADM 
Armor Pharma 
Asahi KASEI 
Ashland 
BASF 
Beneo 
Budenheim 
Captisol 
Clariant 
Croda 
DFE Pharma 
Excipio Chemicals 
Fuji Chemical 
Gattefossé 
Gangwal 
IamFluidics 
IOI Oleo 
Ingredient Pharm 
JRS Pharma 
Kerry 
KLK Oleo 
Lipoid 
Lubrizol Life Science Health 
MAGNESIA 
MEGGLE 
Nagase Viita 
Nordic Bioproducts 
Pfanstiehl 
pharm-a-spheres 
PMC Isochem 
Seppic 
ShinEtsu 
Sigachi 
SPI Pharma 
Südzucker 
Vikram Thermo 
Zerion Pharma 
All4Nutra
- Suppliers
ADM Armor Pharma Asahi KASEI Ashland BASF Beneo Budenheim Captisol Clariant Croda DFE Pharma Excipio Chemicals Fuji Chemical Gattefossé Gangwal IamFluidics IOI Oleo Ingredient Pharm JRS Pharma Kerry KLK Oleo Lipoid Lubrizol Life Science Health MAGNESIA MEGGLE Nagase Viita Nordic Bioproducts Pfanstiehl pharm-a-spheres PMC Isochem Seppic ShinEtsu Sigachi SPI Pharma Südzucker Vikram Thermo Zerion Pharma - All4Nutra
A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats
A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats
Abstract
Aim
Highlights
- The intestinal effective permeability was moderate for ARV-110 and low for ARV-471 in rats.
- Intestinal P-gp contributes to limited intestinal permeability of ARV-110 and ARV-471.
- CYP3A seems to play minor role in first-pass metabolism of ARV-110 and ARV-471.
- The CRBN-based PROTACs undergo luminal enzyme-mediated degradation pre-absorption.
Methods
Results and discussion
Conclusion
In the rat, ARV-110 and ARV-471 were enzymatically degraded in the intestinal lumen and in plasma, and their intestinal permeability and systemic exposure seem to be reduced due to P-gp efflux.
Download the full article as PDF here: A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats
or read it here
2.1. Model compounds and other chemicals
ARV-110 (purity > 98 %) and ARV-471 (purity > 95.4 %) were purchased from Excenen PharmaTech Co., Ltd. (Shanghai, China). Ketoconazole and 4-(2-aminoethyl)-benzene-sulfonyl fluoride (Pefabloc® SC) as well as HPLC grade dimethyl sulfoxide (DMSO), Cremophor EL, D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), carboxymethyl cellulose (CMC), sodium chloride (NaCl) and potassium dihydrogen phosphate (KH2PO4) were supplied by Sigma-Aldrich (St. Louis, MO, USA). Polyethylene glycol 400 (PEG400) was obtained from Thermo Fisher Scientific (Waltham, MA, USA). Encequidar mesylate was purchased from TargetMol Chemicals Inc. (Boston, MA, USA).
Janis Niessen, Nathalie Arendt, Markus Sjöblom, Ilse R. Dubbelboer, Thomas Borchardt, Mirko Koziolek, Mikael Hedeland, Hans Lennernäs, Anura Indulkar, David Dahlgren, A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats, European Journal of Pharmaceutics and Biopharmaceutics, Volume 211, 2025, 114719, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2025.114719.
See also the interesting video on Vitamin E TPGS below and read more: here
