Cyclotraxin B is highly potent and selective TrkB receptor antagonist that inhibits BDNF-induced TrkB activity (IC50 = 0.30 nM). It allosterically changes the conformation of TrkB receptor, but does not change BDNF binding.
CAT No: R0881
CAS No:1203586-72-4
Synonyms/Alias:Cyclotraxin B;1203586-72-4;Cyclotraxin B acetate;(3S,6R,11R,17S,20S,23S,26S,32S,35S)-6-amino-20-(4-aminobutyl)-3-(2-amino-2-oxoethyl)-17-(2-carboxyethyl)-23-[(1R)-1-hydroxyethyl]-26-[(4-hydroxyphenyl)methyl]-32-(2-methylsulfanylethyl)-2,5,13,16,19,22,25,28,31,34-decaoxo-8,9-dithia-1,4,12,15,18,21,24,27,30,33-decazabicyclo[33.3.0]octatriacontane-11-carboxylic acid;DTXSID501045820;AKOS024458477;AS-85368;DA-72492;PD079892;G14323;S-1203586-72-4;
Cyclotraxin B is a synthetic cyclic peptide known for its highly specific antagonistic activity against the TrkB (tropomyosin receptor kinase B) receptor, a key player in neurotrophin signaling pathways. As a structurally constrained peptide, it exhibits remarkable stability and target selectivity, making it a valuable biochemical tool for dissecting molecular mechanisms underlying neuronal growth, differentiation, and synaptic plasticity. The compound's unique ability to modulate TrkB signaling without affecting related receptors has positioned it as an important reagent in neurobiology and receptor pharmacology research. Its applications span a range of experimental contexts where precise inhibition of TrkB-mediated processes is required for mechanistic elucidation or pathway validation.
Neurotrophin pathway research: Cyclotraxin B is widely utilized in studies aimed at unraveling the complexities of neurotrophin signaling, especially those involving brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB. By selectively inhibiting TrkB, researchers can delineate the specific contributions of this receptor to downstream signaling cascades, neuronal survival, and synaptic modulation. Such investigations are critical for understanding the molecular underpinnings of neuronal development and plasticity, as well as the broader biological roles of neurotrophins in the central nervous system.
Receptor pharmacology: The cyclic peptide serves as a robust tool for characterizing the pharmacological properties of TrkB and related receptor tyrosine kinases. Through its potent and selective antagonism, Cyclotraxin B enables detailed analyses of ligand-receptor interactions, receptor activation dynamics, and the structural determinants of selective inhibition. These studies support the development of new strategies for targeting neurotrophin receptors in a research context and contribute to the refinement of receptor-specific assay systems.
Peptide-functional studies: Researchers frequently employ Cyclotraxin B in peptide structure-activity relationship (SAR) investigations to explore how cyclic constraints and sequence modifications influence receptor binding affinity and selectivity. Its well-defined cyclic structure provides a reference point for designing and optimizing novel peptide-based inhibitors or modulators of protein-protein interactions. Such work is essential for advancing the broader field of peptide therapeutics research, particularly with respect to neurotrophin receptor modulation.
Cellular signaling analysis: In vitro and ex vivo systems benefit from the use of Cyclotraxin B to dissect the cellular consequences of TrkB inhibition. By applying the peptide to neuronal cultures or tissue preparations, scientists can monitor alterations in intracellular signaling pathways, such as MAPK/ERK or PI3K/Akt, that are regulated by TrkB activation. This approach facilitates the identification of downstream effectors, feedback mechanisms, and compensatory responses within complex signaling networks.
Target validation in model systems: Cyclotraxin B is instrumental in validating the functional relevance of TrkB in diverse experimental models, including genetically modified cell lines and primary neuronal cultures. Its ability to provide acute, reversible, and highly selective inhibition allows researchers to temporally control TrkB signaling, thereby distinguishing direct receptor-mediated effects from long-term compensatory changes. Such applications are particularly valuable in preclinical studies seeking to establish causal relationships between receptor activity and observed cellular or molecular phenotypes.
Cocaine exposure alters brain-derived neurotrophic factor (BDNF) expression in the brain. BDNF signaling through TrkB receptors differentially modulates cocaine self-administration, depending on the brain regions involved. In the present study, we determined how brain-wide inhibition of TrkB signaling affects cocaine intake, the motivation for the drug, and reinstatement of drug taking after extinction. To overcome the inability of TrkB ligands to cross the blood–brain barrier, the TrkB antagonist cyclotraxin-B was fused to the nontoxictransduction domain ofthetat proteinfrom human immunodeficiency virustype 1 (tat-cyclotraxin-B). Intravenous injection of tat-cyclotraxin-B dose-dependently reduced cocaine intake, motivation for cocaine (as measured under a progressive ratio schedule of reinforcement), and reinstatement of cocainetaking in rats allowed either short or long accessto cocaine self-administration.
Systemic Delivery of a Brain-Penetrant TrkB Antagonist Reduces Cocaine Self-Administration and Normalizes TrkB Signaling in the Nucleus Accumbens and Prefrontal Cortex
By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal) activities.
Cyclotraxin-B, the First Highly Potent and Selective TrkB Inhibitor, Has Anxiolytic Properties in Mice
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