Due to the advancement in techniques for detection and characterization of receptors, and in particular of G protein-coupled receptors (GPCRs) [8,9,10,11,12], the availability of suitable probes is a constant need. of covalent ligands in GPCR structural biology. In this review, an updated collection of available chemical probes targeting adenosine receptors is reported. Keywords: adenosine receptors, fluorescent ligands, radioligands, radiotracers, covalent ligands, GPCR probes 1. Introduction Since their discovery in the mid Octreotide seventies [1,2], adenosine receptors (ARs) have attracted research interest for their implication in a wide range of physiological and pathological processes (i.e., asthma, ischemia, cancer, Parkinsons disease, etc.) [3]. As a consequence, at the same time study commenced on specific receptor probes that are essential tools for receptor characterization [4,5]. ARs exist as four different subtypes: A1, A2A, A2B and A3 ARs [6,7]. Due to the advancement in techniques for detection and characterization of receptors, and in particular of G protein-coupled receptors (GPCRs) [8,9,10,11,12], the availability of IL-23A appropriate probes is a constant need. In particular, this review covers three specific chemical probe family members for ARs: radioactive, covalent and fluorescent ligands. Radioactive ligands, properly called radioligands, are the oldest class of AR probes, and still represent the principal tool in drug finding since their use in binding assays [7]. Recently, the broad desire for radioactive ligands is Octreotide due to their development as radiotracers in positron emission tomography (PET), leading to new diagnostic options [13,14]. On the other hand, covalent ligands for GPCRs, which were in the past used as tools to purify, isolate or pharmacologically characterize receptors, have recently captivated the interest of the medical community for his or her ability to stabilize their target protein, increasing the probability of Octreotide obtaining X-ray crystal constructions [10]. This strategy was successfully applied for the A1 AR subtype [15,16]. Since A2B and A3 AR crystal constructions are still lacking, it is easy to imagine that several works will focus on development of covalent ligands for these receptor subtypes in the near future. Finally, the last few years have been characterized by the application of a variety of fluorescence-based methods for GPCR structure biology and drug discovery [17]. These techniques involve the intro of a fluorescent tag on a GPCR or on a GPCR ligand, leading to fluorescent ligands, which are discussed here [9,18,19,20]. The aim of this review is definitely Octreotide to give a panorama of the available chemical probes for the ARs to experts working in this field or medicinal chemists working on ARs or additional GPCR focuses on. 2. Radioligands and Radiotracers It is well known, that radioligand probes are useful for studying both the distribution and functions of receptors. In this class of compounds, two families of derivatives should be considered: i) radioligands, generally tritiated or iodinated, for binding studies; ii) radioligands utilized for imaging, in general probes including isotopes such as 11C, 18F and 15O. In the first class of compounds, in the last decades, several examples of radioligands for those AR subtypes, both agonists and antagonists, with different examples of potency and selectivity have been reported and extensively examined [7,21,22,23,24]. Our purpose is definitely to give a brief upgrade of the work developed with this field with this review. Considering labeled derivatives for binding studies only an agonist for A2B AR named [3H]-BAY60-6583 (1) was recently reported from the group of Prof. C.A. Mller (Number 1) [25]. Open in a separate window Number 1 Structure of BAY60-6583. This partial agonist in its tritiated form (the position of tritium is not reported) failed to be a good probe for binding studies. This is probably due to its moderate affinity in the human being A2B receptor and higher level of non-specific binding. The only results obtained.