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Leveraging multi-organ models for drug combination therapy safety
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DOI：10.1016/j.biopha.2025.118847.png)
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Abstract
En 中文
• Proposed in vitro platform rapidly identifies systemic toxicities of multidrug combinations. • C2 & REMP combos show organ-specific toxicities undetectable in single-organ screens. • Model differentiation is not always essential but critically improves toxicity detection sensitivity. • Drug-drug interactions potentiate toxicity in specific organ models. • Ready-to-use platform enables early integration into phenotypic screening, optimizing safer multidrug combinations.
Keywords:
ADME
Absorption, Distribution, Metabolism, and Elimination
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
CTG
CellTiter-Glo®
Cx43
Connexin 43
C2
multidrug combination composed of erlotinib HCl, dasatinib, tubacin and tacedinaline
DHepaRG
Differentiated HepaRG cells
DH9c22-1
Differentiated H9c22-1 cells
DMEM
Dulbecco’s Modified Eagle Medium
DMF
Dimethylformamide
DMSO
Dimethyl Sulfoxide
FBS
Fetal Bovine Serum
HEK293T
Human Embryonic Kidney 293T cells
IPSC
Induced pluripotent stem cells
LDH
lactate dehydrogenase
NdHepaRG
Non-differentiated HepaRG cells
NdH9c22-1
Non-differentiated H9c22-1 cells
RA
all-trans Retinoic Acid
REMP
multidrug combination composed of erlotinib HCl, parthenolide, metformin HCl, and RAPTA-C
RPTEC
Renal Proximal Tubule Epithelial Cells
TGMO
Therapeutically Guided Multidrug Optimization
ODCs
Optimized Drug Combinations
cancer
cardiotoxicity
drug combination
drug-drug interaction
hepatotoxicity
in vitro
nephrotoxicity
screening
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Journal
B
IF:
7.5
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1.6W
Citations:
8.2W
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