Representative compounds

Probes (Available for collaboration)

Name Structure Target TOC Introduction
TiNIR HMOX2 protein

Tumor initiating cell

TiNIR selectively detects heme oxygenase 2 (HMOX2) as a novel biomarker for TIC, and enriches the functionally active TIC in human lung tumors. Through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, TiNIR can inhibit tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. J. Am. Chem. Soc. 2019, 141, 14673.
BacGO Peptidoglycan

Gram-positive bacteria

BacGO, a novel Gram‐positive bacterial probe, was developed from a library of fluorescent molecules with a boronic‐acid motif that binds to peptidoglycan on the Gram‐positive bacterial cell wall. BacGO can be used to identify Gram‐positive bacteria in diverse, highly complex samples, and is an attractive alternative to Gram staining. Angew. Chem. Int. Ed. Engl. 201958, 7972.
CDr20 Ugtla7c protein


Using a thorough structure-activity relationships study, we developed CDr20, a high‐performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome‐scale CRISPR‐Cas9 knockout screen, the UDP‐glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence. Angew. Chem. Int. Ed. 2019, 58, 7972.
CDg16    Orphan transporter Slc18b1

Activated macrophage

CDg16 is a small molecule probe specific for activated macrophages and can be applied to visualize inflammatory atherosclerotic plaques in vivo. Through a systematic transporter screen using a CRISPR activation library, we identify the orphan transporter Slc18b1/SLC18B1 as the gating target of CDg16Nat. Commun. 201910, 1111.
ElaNIR Elastin The NIR zwitterionic elastin probe ElaNIR (elastin NIR) was discovered through fluorescent-image-based screening. The probe was successfully applied for in vitro, ex vivo, and in vivo imaging by various imaging modalities. Age-related elastin differences shown by in vivo fluorescent and photoacoustic imaging indicated that ElaNIR can be a potentially convenient tool for uncovering changes of elastin in live models. Chem 20184, 1128.
TiY Vimentin

Tumor initiating cell

TiY is the first TIC‐specific fluorescent chemical probe with the molecular target of vimentin, a marker for epithelial‐to‐mesenchymal transition (EMT). TiY selectively stains TICs over differentiated tumor cells or normal cells, and facilitates the visualization and enrichment of functionally active TICs from patient tumors. At high concentration, TiY shows anti‐TIC activity with low toxicity to non‐TICs. Angew. Chem. Int. Ed. Engl. 201857, 2851.



TP-β is a 2-glucosamine-based two-photon fluorescent probe, which is suitable for imaging of beta cells in live pancreatic islets from mice. Flow cytometry studies confirmed that TP-β is suitable for isolation of primary beta cells. Moreover, two-photon imaging of TP-β-stained pancreatic islets showed brightly stained beta cells in live islets. Insulin enzyme-linked immunosorbent assays revealed that TP-β has no effect on glucose-stimulated insulin secretion from the stained islet. J. Am. Chem. Soc. 2017139, 3480.


Pancreatic alpha cell

The first TP live pancreatic islet imaging probe, TP-α (Two Photon-alpha), can selectively stain glucagon secreting alpha cells. In vitro fluorescence test showed that TP-α have direct interaction and appear glucagon with a significant fluorescence increase, but not with insulin or other hormones/analytes. Finally, TP-α was successfully applied for 3D imaging of live islets by staining alpha cell directly. J. Am. Chem. Soc. 2015137, 5355.
 CDg13 Abcg2 transporter

 Neurogenic neural stem/progenitor cells

CDg13, a new fluorescent substrate for the Abcg2 transporter, facilitated the isolation of neurogenic neural stem/progenitor cells (NSPCs) from embryonic mouse brain. The high sensitivity and selectivity of CDg13 to Abcg2 make the probe as a very useful tool to measure Abcg2 activity in live cells. ChemBioChem 2016, 17, 2118.
CDy1 Pluripotent stem cells CDy1, a PSC specific fluorescent probe, was investigated for the generation of reactive oxygen species (ROS) and demonstrated to induce selective death of PSC upon visible light irradiation. Importantly, the CDy1 and/or light irradiation did not negatively affect differentiated endothelial cells. The photodynamic treatment of PSC with CDy1 and visible light irradiation confirmed the inhibition of teratoma formation in mice. ACS Cent. Sci. 2016, 2, 604.
CO-1 &


CO-1 and AzG-1, a cyclooctyne- and azide-containing BODIPY probe, respectively, can specifically label intracellular target organelles and engineered proteins with minimum background. They provide an efficient strategy for development of background-free probes, referred to as ‘tame’ probes, and novel tools for live cell intracellular imaging. Nat. Commun. 20167, 11964.
ATP-Red 1 ATP A multisite‐binding, switchable fluorescent probe can selectively and rapidly respond to ATP at intracellular concentrations. In live‐cell imaging, the probe, ATP-Red 1 was successfully applied to monitor fluctuations in mitochondrial ATP levels. Angew. Chem. Int. Ed. 201655, 1773.
CDy11 Bacterial amyloid

Pathogenic biofilm

CDy11 (compound of designation yellow 11), which targets amyloid in the Pseudomonas aeruginosa biofilm matrix, was discovered through a diversity-oriented fluorescent library approach (DOFLA). CDy11 was further demonstrated for in vivo imaging of P. aeruginosa in implant and corneal infection mice models. J. Am. Chem. Soc. 2016138, 402.
BD-Oligo Aβ Oligomers The oligomer-specific fluorescent chemical probe, BoDipy-Oligomer (BD-Oligo), was developed through the use of the diversity-oriented fluorescent library approach (DOFLA) and high-content, imaging-based screening. This probe enables dynamic oligomer monitoring during fibrillogenesis in vitro and shows in vivo Aβ oligomers staining possibility in the AD mice model. J. Am. Chem. Soc. 2015137, 13503.
CDy9 Mouse embryonic stem cell CDy9 is a highly reliable probe for the specific detection of live stem cells. CDy9 allows the detection and isolation of intact stem cells with marginal impact on their function and capabilities. Bioorg. Med. Chem. Lett. 201525, 4862.
CDb12 Nucleus A low-toxicity nucleus staining fluorescent probe, CDb12, was developed for real time mitosis imaging in live cells. CDb12 was identified by unbiased high-throughput imaging-based screening of a new xanthone library (AX). Unlike the conventional Hoechst dye, the low toxicity of CDb12 allows long term monitoring of cell division over more than one cell cycle. Chem. Commun. 201551, 9336.
CDy6 Lysosome CDy6 is a dye to mark mitotic cells. CDy6 displays numerous favorable properties including showing a sharp increase in intensity and change in localization in mitosis, improved photostability, and decreased toxicity compared with other widely used lysosomal markers in long-term real-time imaging. Chem. Biol. 201522, 299.
NeuO Neuron To address existing limitations in live neuron imaging, we have developed NeuO, a novel cell-permeable fluorescent probe with an unprecedented ability to label and image live neurons selectively over other cells in the brain. NeuO enables robust live neuron imaging and isolation in vivo and in vitro across species; its versatility and ease of use sets the basis for its development in a myriad of neuronal targeting applications. Angew. Chem. Int. Ed. 201554, 2442.

Neural stem cell

  The neural stem cell (NSC)-specific probe (CDr3), was developed through a high throughput/content screening of diversity-oriented fluorescence library in stem cells at different developmental stages. CDr3 specifically detects living neural stem cells of both human and mouse origin. Furthermore, the binding target was identified by proteomic analysis as fatty acid binding protein 7 (FABP7), which is highly expressed in neural stem cells and localized in the cytoplasm. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 10214. 
CDg4 Glycogen

Mouse embryonic stem cell

CDg4, a novel green fluorescent mESC probe was discovered through a high-content image based screening of 160 members of the chalcone library. Interestingly, the molecular binding target of CDg4 was identified as the glycogen of the stem cell colony surface, rather than a conventional protein target from an intracellular source. Chem. Commun. 2012, 48, 6681.


To investigate intracellular binders of myotube‐specific probes, a thiol‐reactive derivative, CDy2, was prepared. In live cells, the derivative selectively localizes in mitochondria and covalently labels its binding partners. Angew. Chem. Int. Ed. 2011, 50, 2761.
Glucagon Yellow Glucagon

Alpha cell

The first BODIPY library (BD) was synthesized, and a highly selective glucagon sensor, Glucagon Yellow (BD-105), was discovered by fluorescence image-based screening method. Glucagon Yellow exhibited selective staining only in AlphaTC1 cells. The selectivity of Glucagon Yellow toward glucagon was confirmed in vitro by comparison of its fluorescence intensity change against 19 biologically relevant analytes. J. Am. Chem. Soc. 2009, 131, 10077.
Heparin Blue Heparin Heparin Blue was developed by a diversity-oriented fluorescence library approach (DOFLA) from a benzimidazolium library; the discovered compound showed remarkable properties and have the potential to be applied to monitoring heparin levels in clinical plasma samples for point-of-care detection. Chem. Commun. 2008, 1173.
G13 HSA A fluorescent dye library approach for the development of a bioanalyte sensor was sought. The screening of a rosamine dye library against diverse macromolecules led to the discovery of a highly sensitive human serum albumin binder, G13, with ∼36-fold fluorescence intensity change. G13 showed a highly selective response to HSA over other macromolecules including albumins from other species. The potential use of G13 for the detection of HSA in biofluids is described. J. Comb. Chem. 2008, 10, 376.
STB-8 Amyloid plaques A group of styryl‐based neutral compounds has been developed as potential imaging agent candidates for the β‐amyloid plaques seen in Alzheimer’s disease (AD). The representative compound STB‐8 successfully penetrated the blood-brain barrier and specifically stained amyloid plaques of AD model transgenic mice ex vivo and in vivo. ChemBioChem 2007, 8, 1679.
RS-H22 GSH Combinatorial approach on fluorescent rosamine library was developed using solid-phase chemistry. A highly selective library member (H22) toward reduced glutathione (GSH) was discovered, demonstrating the capability of in vivo GSH level sensing in live cells. J. Am. Chem. Soc. 2007, 129, 4510.







RNA This protocol outlines a methodology for the preparation and characterization of three RNA-specific fluorescent probes (E36, E144 and F22) and their use in live cell imaging. It describes a detailed procedure for their chemical synthesis and purification; serial product characterization and quality control tests, including measurements of their fluorescence properties in solution, measurement of RNA specificity and analysis of cellular toxicity; and live cell staining and counterstaining with Hoechst or DAPI. Preparation and application of these RNA imaging probes take 1 week. Nat. Protoc. 2006, 1, 2922.
GTP Green GTP Highly selective fluorescence turn-on GTP sensor, GTP Green, was discovered by a diversity directed sensor approach, combined by solid-phase combinatorial synthesis of a benzimidazolium library and high-throughput screening. J. Am. Chem. Soc. 2006, 128, 10380.


40 & Aβ42 fibril A library of fluorescent styryl dyes (320 compounds) was prepared by solid‐phase chemistry. The dyes were screened for their detection of amyloid aggregates, which are associated with diseases such as Alzheimer’s, and two of the 320 compounds screened, 2C40 and 2E10, showed promise as brain‐imaging agents. Angew. Chem. Int. Ed. 2004, 43, 6331.

Sensors (Available for collaboration)

Name Structure Target TOC Introduction
Mito Thermo Yellow (MTY) Temperature


Mito thermo yellow was applied to measure mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 °C, mitochondria were more than 10 °C warmer (close to 50 °C) when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. PLoS Biol. 2018, 16, e2003992.325. Chem. Commun. 201551, 8044.
 ERThermAC Temperature

Endoplasmic Reticulum

ERthermAC was developed to monitor thermogenesis in BAs derived from murine brown fat precursors and in human brown fat cells differentiated from human neck brown preadipocytes. ERthermAC accumulated in the endoplasmic reticulum of BAs and displayed a marked change in fluorescence intensity in response to adrenergic stimulation of cells, which corresponded to temperature change. Sci. Rep. 20177, 1383.
ER Thermo Yellow Temperature

Endoplasmic Reticulum

ER thermo yellow is the first small molecule fluorescent thermometer selectively targeting the endoplasmic reticulum, with the highest sensitivity reported so far (3.9%/°C). Unlike nanoparticle thermometers, ER thermo yellow stains the target organelle evenly without the commonly encountered problem of aggregation, and successfully demonstrates the ability to monitor intracellular temperature gradients generated by external heat sources in various cell types. We further confirm the ability of ER thermo yellow to monitor heat production by intracellular Ca2+ changes in HeLa cells. Sci. Rep. 20144, 6701.
BTV Viscosity


A simple BODIPY-based probe, BTV, was developed for cellular mitochondria viscosity imaging. BTV exhibited a significant fluorescence intensity enhancement as the solvent viscosity increased and showed a direct linear relationship between the fluorescence lifetime and the media viscosity. BTV could achieve practical applicability in the monitoring of mitochondrial viscosity changes in live cells through fluorescence lifetime imaging microscopy (FLIM). Sensors 201616, 1397.