HTS010M - ChemiSCREEN™ Rehsus Macaque CCR5 Chemokine Receptor Membrane Preparation

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HTS010M
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    CCR5 is the receptor for CC chemokines MIP-1a, MIP-1b, and RANTES (Raport et al., 1996), and is preferentially expressed on Th1 lymphocytes (Loetscher et al., 1998). CCR5 is a coreceptor for macrophage-tropic HIV, and its ligands potently inhibit HIV replication in human leukocytes (Cocchi et al., 1995). In addition, HIV-infected patients with the nonfunctional CCR5D32 allele exhibit delayed onset of AIDS symptoms (Samson et al., 1996), and pharmacological antagonism of CCR5 inhibits HIV-1 infection (Strizki et al., 2001). Preclinical testing of small molecule antagonists of CCR5 has been hampered by low affinity of the compounds to rodent and dog CCR5, but two such compounds, maraviroc and AD101, have been shown to have potent antagonist activity at rhesus macaque CCR5, which differs from human CCR5 by 8 amino acids (Napier et al., 2005; Billick et al., 2004). One antagonist of human CCR5, SCH-C, does not block HIV entry through rhesus macaque CCR5, and one amino acid difference is responsible for the functional difference (Billick et al., 2004). Rhesus macaque CCR5 membrane preparations are crude membrane preparations made from our proprietary stable recombinant cell lines to ensure high-level of GPCR surface expression; thus, they are ideal HTS tools for screening of agonists and antagonists of rCCR5.

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    Item Unit of Measure: EA
    Quantity: 200 units
    Storage: On receipt of material store at -70°C. Unopened reagent is stable for a minimum of 1 year from date of shipment when stored at recommended storage temperature. Avoid repeat freeze/thaw cycles.
    Applications: Radioligand Binding Assay
    Host Cell: Chem-1, an adherent cell line expressing the promiscuous G-protein, Ga15.
    Reference 1: 1. Abdi, R, et al. (2002) The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection. Diabetes 51: 2489-2495.
    Reference 2: 2. Belnoue, E, et al. (2003) CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 101: 4253-9.
    Reference 3: 3. Cocchi, F., et al. (1995) Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270: 1811-1815.
    Reference 4: 4. Loetscher, P, et al. (1998) CCR5 is characteristic of Th1 lymphocytes. Nature 391: 344-5.
    Reference 5: 5. Raport CJ, et al. (1996) Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem 271: 17161-6.
    Reference 6: 6. Samson, M, et al. (1996) Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382: 722-5.
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