Small-molecule organic fluorophores, spectrally active in the 900-1700 nm region, with tunable wavelength and sensing properties are sought-after for in vivo optical imaging and biosensing. A panel of fluorescent dyes (CX) has been developed to meet this challenge. CX dyes exhibit the wavelength tunability of cyanine dyes and have a rigidified polymethine chain to guarantee their stability. They are chemo- and photo-stable in an aqueous environment and have tunable optical properties with maximal absorbing/emitting wavelength at 1089/1140 nm. They show great potential in high-contrast in vivo bioimaging and multicolor detection with negligible optical cross talk. Förster resonance energy transfer (FRET) between CX dyes was demonstrated in deep tissue, providing an approach for monitoring drug-induced hepatotoxicity by detection of OONO . This report presents a series of NIR-II dyes with promising spectroscopic properties for high-contrast bioimaging and multiplexed biosensing.