Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CGP 53437 is a peptidomimetic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease containing a hydroxyethylene isostere. The compound inhibited recombinant HIV-1 protease with a Ki of 0.2 nM. The inhibition constant versus human cathepsin D and human cathepsin E was 4 nM. Human pepsin and gastricsin were inhibited with Kis of 8 and 500 nM, respectively, and human renin was inhibited with a Ki of 190 microM. The replication of HIV-1/LAV, HIV-1/Z-84, and HIV-1/pLAI was inhibited with a 90% effective dose of 0.1 microM in acutely infected MT-2 cells. The 50% cytotoxic dose was 100 microM. Similar antiviral activity was observed when the compound was added up to 10 h after infection. At the effective concentration, processing of Gag precursor protein p55 was greatly reduced, confirming an action on the late stage of the virus life cycle, as expected. The efficacy of the inhibitor was also demonstrated by using primary human peripheral blood lymphocytes infected with the HIV-1/LAV strain, low-passage clinical isolates obtained from HIV-1-seropositive individuals (including a zidovudine-resistant strain), and HIV-2/ROD. In these cells, CGP 53437 delayed the onset of HIV replication in a dose-dependent fashion (substantial effects with concentrations of > or = 0.1 microM) as long as the inhibitor was maintained in the culture. CGP 53437 was orally bioavailable in mice. Concentrations in plasma 10-fold in excess of the in vitro antiviral 90% effective dose could be sustained for several hours after oral application of 120 mg/kg. Therefore, CGP 53437 has the potential to be a therapeutically useful anti-HIV agent for the treatment of AIDS.
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PMID:CGP 53437, an orally bioavailable inhibitor of human immunodeficiency virus type 1 protease with potent antiviral activity. 825 28

To characterize proteins involved in melanoma dissemination, protein profiles from B16F10 and B16Bl6 cells were compared, as only B16Bl6 cells give pulmonary metastases after subcutaneous graft. As B16F10 and B16Bl6 cells had the same invasive capacities in vitro, we wondered whether their extracellular content could be different and correlate with their metastatic properties. We have shown that B16F10 and B16Bl6 culture cell supernatants have different modulatory effects on HT1080 fibrosarcoma cell invasion in Matrigel-coated chambers. B16Bl6 supernatants significantly enhanced HT1080 in vitro invasion as compared with B16F10 ones, suggesting differences in their protein profiles. Indeed, proteomic analysis allowed the identification of 18 differential proteins. Among the proteins with a higher concentration in B16Bl6 supernanants, lactate dehydrogenase B, M2 pyruvate kinase, cathepsin D, and galectin 1 were involved in the melanoma aggressiveness signature. Interestingly, several Gag retroviral proteins, as well as syntenin, were found mainly in the B16F10 secretome. Although its intracellular form is known as an aggressive melanoma marker, we show for the first time that syntenin was actively secreted and could reduce the invasion process, probably by protein interactions in the B16 model.
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PMID:B16 melanoma secretomes and in vitro invasiveness: syntenin as an invasion modulator. 2001 92