alx40-4c has been researched along with plerixafor* in 4 studies
1 review(s) available for alx40-4c and plerixafor
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[Development of anti-HIV drugs targeted to the coreceptors].
Topics: Amino Acid Sequence; Animals; Anti-HIV Agents; Antimicrobial Cationic Peptides; Benzylamines; Chemokine CCL5; Cyclams; Heterocyclic Compounds; HIV-1; Humans; Ligands; Molecular Sequence Data; Oligopeptides; Peptides; Receptors, Chemokine | 1998 |
3 other study(ies) available for alx40-4c and plerixafor
Article | Year |
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A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C are weak partial agonists.
CXCR4 is a G protein-coupled receptor for stromal-derived factor 1 (SDF-1) that plays a critical role in leukocyte trafficking, metastasis of mammary carcinoma, and human immunodeficiency virus type-1 infection. To elucidate the mechanism for CXCR4 activation, a constitutively active mutant (CAM) was derived by coupling the receptor to the pheromone response pathway in yeast. Conversion of Asn-119 to Ser or Ala, but not Asp or Lys, conferred autonomous CXCR4 signaling in yeast and mammalian cells. SDF-1 induced signaling in variants with substitution of Asn-119 to Ser, Ala, or Asp, but not Lys. These variants had similar cell surface expression and binding affinity for SDF-1. CXCR4-CAMs were constitutively phosphorylated and present in cytosolic inclusions. Analysis of antagonists revealed that exposure to AMD3100 or ALX40-4C induced G protein activation by CXCR4 wild type, which was greater in the CAM, whereas T140 decreased autonomous signaling. The affinity of AMD3100 and ALX40-4C binding to CAMs was less than to wild type, providing evidence of a conformational shift. These results illustrate the importance of transmembrane helix 3 in CXCR4 signaling. Insight into the mechanism for CXCR4 antagonists will allow for the development of a new generation of agents that lack partial agonist activity that may induce toxicities, as observed for AMD3100. Topics: Amino Acid Substitution; Animals; Anti-HIV Agents; Benzylamines; CHO Cells; Cricetinae; Cyclams; Genes, Reporter; Genetic Variation; GTP-Binding Proteins; Heterocyclic Compounds; Humans; Oligopeptides; Open Reading Frames; Point Mutation; Protein Conformation; Receptors, CXCR4; Recombinant Proteins; Saccharomyces cerevisiae; Signal Transduction; Transfection | 2002 |
Increase of R5 HIV-1 infection and CCR5 expression in T cells treated with high concentrations of CXCR4 antagonists and SDF-1.
The chemokine receptors CXCR4 and CCR5 are considered to be potential targets for the inhibition of HIV-1 replication. We found that the synthetic peptides T134 and T140 (see text for full names) inhibited X4 HIV-1 infection with selectivity and low toxicity because they acted as CXCR4 antagonists. However, high concentrations of T134, T140, and ALX40-4C (see text for full name) increased the expression of CCR5 and R5 HIV-1 infection, as did stromal cell-derived factor 1 (SDF-1). In contrast to CXCR4 antagonists and SDF-1, viral monocyte inflammatory protein (vMIP) II inhibited not only anti-CXCR4 monoclonal antibody (MAb) but also inhibited anti-CCR5 MAb binding to human peripheral blood mononuclear cells, and inhibited both X4 and R5 HIV-1 strains. T134, T140, ALX40-4C, and SDF-1 increased viral transcription in the treated cells. In addition, ALX40-4C and SDF-1 also increased nuclear transcription factor (NF)-kappaB. However, the mechanisms of action of T134 and T140 are different from those of clinically used anti-HIV drugs. Thus, synergistic activities were observed in the concomitant treatment with T134 and reverse transcriptase inhibitors or protease inhibitors. Our findings, presented here, are noteworthy in regard to the potential clinical use of these agents as drugs for the treatment of AIDS. Topics: Animals; Anti-HIV Agents; Antibodies, Monoclonal; Benzylamines; CD4 Antigens; CD4-Positive T-Lymphocytes; Chemokine CXCL12; Chemokines; Chemokines, CXC; Chlorocebus aethiops; COS Cells; Cyclams; Drug Synergism; Gene Expression Regulation; Heterocyclic Compounds; HIV Long Terminal Repeat; HIV-1; Humans; Methionine; Oligopeptides; Peptide Fragments; Receptors, CCR5; Receptors, CXCR4; Transfection; Tumor Cells, Cultured; Virus Replication; Zidovudine | 2001 |
A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140.
T22 ([Tyr5,12, Lys7]-polyphemusin II) is an 18-residue peptide amide, which has strong anti-HIV activity. T22 inhibits the T cell line-tropic (T-tropic) HIV-1 infection through its specific binding to a chemokine receptor CXCR4, which serves as a coreceptor for the entry of T-tropic HIV-1 strains. Herein, we report our finding of novel 14-residue CXCR4 inhibitors, T134 and T140, on the basis of the T22 structure. In the assays we examined, T140 showed the highest inhibitory activity against HIV-1 entry and the strongest inhibitory effect on the binding of an anti-CXCR4 monoclonal antibody (12G5) to CXCR4 among all the CXCR4 inhibitors that have been reported up to now. Topics: Amino Acid Sequence; Anti-HIV Agents; Antimicrobial Cationic Peptides; Benzylamines; Cells, Cultured; Chemokine CXCL12; Chemokines, CXC; Circular Dichroism; Cyclams; DNA-Binding Proteins; Heterocyclic Compounds; HIV-1; Molecular Sequence Data; Oligopeptides; Peptides; Peptides, Cyclic; Receptors, CXCR4; T-Lymphocytes | 1998 |