Cytochrome P450 3A4 (CYP3A4) is the most important cytochrome P450 enzyme for drug metabolism in humans. Its activity directly determines the efficacy and safety of over 50% of clinical pharmaceuticals.
Traditional detection methods relying on mass spectrometry are limited by high costs and complex workflows, restricting their deep application in complex biological systems. To overcome this bottleneck, the research team led by Professor Ge Guangbo at Shanghai University of Traditional Chinese Medicine integrated computational intelligent design, AI-based drug-likeness screening, and cross-platform validation to successfully develop two novel CYP3A4-specific fluorescent substrates—NCN and NFa.
NCN: Multi-dimensional Dynamic Monitoring & Mass Spectrometry-free Quantification
NCN avoids interference from P-glycoprotein (P-gp) and exhibits excellent cell membrane permeability, enabling dynamic CYP3A4 activity monitoring across multiple levels: subcellular fractions, living cells, isolated organs, and live animals. It aims to establish a mass spectrometry-free quantitative detection system, supporting multidimensional dynamic tracking and high-throughput drug screening from subcellular structures to whole organisms.
NFa: In Situ Super-resolution Imaging & Multi-dimensional Modulator Screening
NFa goes further with its oral bioavailability, low toxicity, and endoplasmic reticulum targeting, making it ideal for in situ, real-time super-resolution imaging in living cells, tissues, and animals. It also allows efficient screening and evaluation of CYP3A4 modulators across multiple dimensions—from target enzymes and tissue preparations to cells, organs, and in vivo models.
Together, NCN and NFa form a powerful dual-substrate toolkit that provides unprecedented capabilities for studying cytochrome P450 enzyme function, advancing drug–drug interaction research, and promoting personalized medicine.
| Traditional Mass Spectrometry Methods | NCN/NFa Fluorescent Probe Methods | |
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| Core Principle | Relies on mass spectrometers to detect changes in the molecular weight of metabolites. | Detects changes in fluorescence signal intensity or location to directly reflect enzyme activity. |
| Sample System | Typically relies on human liver microsomes or recombinant enzymes, differing from the real intracellular environment. | Can directly use live cells expressing the enzymes, closer to physiological or pathological states, yielding more accurate results. |
| Spatio-temporal Resolution | Cannot provide real-time dynamic information in living systems; it is an endpoint-based destructive detection method. | NCN: Enables multi-dimensional dynamic activity monitoring. NFa: Possesses super-resolution imaging capabilities that are in situ, real-time, and targeted to specific subcellular organelles. |
| Instrument Cost | Requires expensive mass spectrometers and specialized operators. | Lower detection instrument cost, enabling high-throughput screening. |
| Operation & Time Consumption | Complex procedures, cumbersome sample preparation, and long detection cycles. | Simple operation, rapid reaction, easy to automate, saving significant labor and time. |
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Guangbo Ge, PhD Chair Professor & Executive Vice Dean Shanghai University of Traditional Chinese Medicine |
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Development of innovative drug screening technologies and fluorescence-based molecular probes for real-time monitoring of drug-metabolizing enzymes (particularly cytochrome P450 isoforms). |
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Core Products
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Cat#9456218 NFa, 98%
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Cat#9456220 NCN, 98%
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Cat#9456219 4-HNFa, 98%
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Cat#9456211 HNCN, 98%
艳 李
