FC 131 is an antagonist of CXCR4 with anti-HIV activity
CAT No: 10-101-256
CAS No:606968-52-9
Synonyms/Alias:FC131;606968-52-9;FC 131;Cyclo(-D-Tyr-Arg-Arg-Nal-Gly-);2-[3-[(2S,5S,8S,14R)-5-[3-(diaminomethylideneamino)propyl]-14-[(4-hydroxyphenyl)methyl]-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propyl]guanidine;CHEMBL436283;CHEMBL2180076;Fc-131;Cyclo[2-Nal-Gly-D-Tyr-Arg-Arg];SCHEMBL15987252;CHEBI:183910;GLXC-04293;Cyclo(-Nal-Gly-D-Tyr-Arg-Arg-);HY-P1104;BDBM50166106;BDBM50399002;Cyclo-[2-Nal-Gly-D-Tyr-Arg-Arg];EX-A11275;AKOS040745190;DA-53131;CS-0027759;Cyclo[3-(2-naphthalenyl)-L-alanylglycyl-D-tyrosyl-L-arginyl-L-arginyl];1-[3-[(2S,5S,8S,14R)-5-(3-guanidinopropyl)-14-[(4-hydroxyphenyl)methyl]-8-(2-naphthylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]propyl]guanidine;N-{3-[(2S,5S,8S,14R)-5-(3-carbamimidamidopropyl)-14-[(4-hydroxyphenyl)methyl]-8-(naphthalen-2-ylmethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl]propyl}guanidine;N-{3-[(2S,5S,8S,14R)-5-(3-Guanidino-propyl)-14-(4-hydroxy-benzyl)-8-naphthalen-2-ylmethyl-3,6,9,12,15-pentaoxo-1,4,7,10,13pentaaza-cyclopentadec-2-yl]-propyl}-guanidine;
Chemical Name:cyclo[3-(2-naphthalenyl)-L-alanylglycyl-D-tyrosyl-L-arginyl-L-arginyl]
FC131, also known as a potent and selective chemokine receptor antagonist, is a synthetic carbohydrate-based compound recognized for its unique structure and high affinity for CXCR4. Characterized by its macrocyclic peptide framework and carbohydrate moieties, FC131 demonstrates exceptional stability and specificity in molecular interactions. Its design enables targeted modulation of chemokine receptor pathways, making it a valuable tool in advanced biochemical research. The compound's capacity to disrupt chemokine signaling has opened new avenues in the exploration of cell migration, immune response regulation, and receptor-ligand dynamics. Researchers appreciate the versatility of FC131, as it can be seamlessly incorporated into various in vitro and in vivo experimental systems, supporting a broad spectrum of scientific investigations.
Molecular Pharmacology: FC131 is widely employed in molecular pharmacology studies to investigate the underlying mechanisms of chemokine receptor signaling, particularly those involving CXCR4. By acting as a competitive antagonist, the compound effectively blocks the interaction between CXCR4 and its natural ligand, SDF-1 (CXCL12), thereby allowing researchers to dissect the downstream signaling pathways and their biological consequences. This targeted inhibition facilitates the examination of G-protein coupled receptor (GPCR) functions, receptor desensitization, and internalization processes, offering insights into receptor pharmacodynamics and the modulation of cellular responses.
Cell Migration and Invasion Research: The ability of FC131 to inhibit CXCR4-mediated chemotaxis makes it instrumental in studies focused on cell migration and invasion. Scientists utilize it to model and analyze the movement of immune cells, stem cells, and cancer cells in response to chemokine gradients. By disrupting the SDF-1/CXCR4 axis, the compound helps delineate the molecular cues that govern cellular trafficking and tissue homing. This application is particularly valuable for understanding mechanisms underlying immune surveillance, tissue regeneration, and pathological cell dissemination.
Immune System Modulation: In immunological research, FC131 serves as a critical tool for evaluating the regulation of immune cell trafficking and activation. The compound's antagonistic effect on CXCR4 is leveraged to study the mobilization of hematopoietic stem cells, lymphocyte homing, and the orchestration of immune responses in various disease models. Researchers can manipulate immune cell localization and assess the impact of altered chemokine signaling on inflammation, immune homeostasis, and adaptive immunity, thereby advancing knowledge in immunomodulation and host defense mechanisms.
Receptor-Ligand Binding Assays: The high specificity of FC131 for CXCR4 enables its use in receptor-ligand binding assays, where it acts as a reference antagonist or competitive inhibitor. These assays are fundamental for characterizing novel ligands, screening potential modulators, and quantifying binding affinities. By providing a reliable means to block receptor activity, the compound supports the validation of new chemokine receptor-targeted agents and the development of structure-activity relationship (SAR) models, contributing to the rational design of next-generation pharmacological tools.
Signal Transduction Pathway Analysis: Researchers employ FC131 to probe signal transduction pathways downstream of chemokine receptor activation. By selectively inhibiting CXCR4, the compound allows for the dissection of signaling cascades such as PI3K/AKT, MAPK/ERK, and JAK/STAT in diverse cell types. This application is essential for elucidating the molecular basis of cell proliferation, survival, and differentiation in response to chemokine cues. The insights gained from these studies inform the development of targeted interventions and expand the understanding of cellular communication networks.
Biochemical and Cellular Assays: The versatility of FC131 extends to its integration into a wide array of biochemical and cellular assays designed to evaluate receptor function, cellular signaling, and biological outcomes. Its use in migration assays, calcium flux measurements, and gene expression studies allows for comprehensive assessment of chemokine receptor activity and its impact on cellular physiology. The compound's robust performance in complex experimental systems makes it a preferred choice for academic and industrial laboratories aiming to unravel the intricacies of chemokine-mediated processes and advance the field of receptor biology.
The Arg2 and 2‐Nal3 side chains of FC131 interact with residues in TM‐3 (His113, Asp171) and TM‐5 (hydrophobic pocket) respectively. Arg1 forms charge‐charge interactions with Asp187 in ECL‐2, while D‐Tyr5 points to the extracellular side of CXCR4. Furthermore, the backbone of FC131 interacts with the chemokine receptor‐conserved Glu288 via two water molecules. Intriguingly, Tyr116 and Glu288 form a H‐bond in CXCR4 crystal structures and mutation of either residue to Ala abolishes CXCR4 activity.
Determination of the binding mode for the cyclopentapeptide CXCR4 antagonist FC131 using a dual approach of ligand modifications and receptor mutagenesis
Previously, we developed a highly potent CXC chemokine receptor type 4 (CXCR4) antagonist, FC131 [cyclo(-d-Tyr1-Arg2-Arg3-Nal4-Gly5-)], from a library of cyclic pentapeptides consisting of pharmacophore residues of the polyphemusin-II-derived anti-human immunodeficiency virus (HIV) peptide T140. Since this novel scaffold for CXCR4 antagonists was identified, a series of cyclic peptides and peptidomimetics have been designed for potential anti-HIV and antimetastatic agents.
Structure–Activity Relationship Study of a CXC Chemokine Receptor Type 4 Antagonist, FC131, Using a Series of Alkene Dipeptide Isosteres
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