Disease relevance of AMP

• These analyses support the virological observation that the addition of M46I and I47V mutations on the I50V mutant background enables increased survival of the HIV-1 virus as it replicates in the presence of VX-478 [1].
• Passage of human immunodeficiency virus type-1 (HIV-1) in T-lymphocyte cell lines in the presence of increasing concentrations of the hydroxylethylamino sulfonamide inhibitor VX-478 or VB-11328 results in sequential accumulation of mutations in HIV-1 protease [1].
• Within 10 to 15 weeks of serial passage, three major mutations-I54M, I82F, and L90M-arose in HIV-2 viral cultures exposed to APV, NFV, and IDV, whereas I82L was selected with TPV [2].
• Twenty-seven patients (1 female, 26 males, age 62+/-9 years) with lung cancer or indeterminate pulmonary nodules were studied on the same day with a full-ring PET scanner (Siemens ECAT EXACT) and a coincidence gamma camera system (ADAC Vertex MCD) [3].

Psychiatry related information on AMP

• At GlaxoSmithKline (GSK) and Vertex Pharmaceuticals, this effort focused on two key issues, patient compliance and viral resistance [4].
• Individual differences in auditory electric responses: comparisons of between-subject and within-subject variability. II. Amplitude of brainstem Vertex-positive peaks [5].

High impact information on AMP

• VX-944 (Vertex Pharmaceuticals, Cambridge, MA, USA) is a small-molecule, selective, noncompetitive inhibitor directed against human IMPDH [6].
• Amprenavir (Agenerase, 141-W94, VX-478) is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PRI) recently approved for the treatment of HIV-1 infection in the United States. A major cause of treatment failure is the development of resistance to PRIs [7].
• When the substitutions observed were introduced as single mutations into an HIV-1 infectious clone (HXB2), only the Ile-50-->Val mutant showed reduced sensitivity (two- to threefold) to VB-11,328 and VX-478 [8].
• Human immunodeficiency virus type 1 (HIV-1) variants with reduced sensitivity to the hydroxyethylamino sulfonamide protease inhibitors VB-11,328 and VX-478 have been selected in vitro by two independent serial passage protocols with HIV-1 in CEM-SS and MT-4 cell lines [8].
• DNA sequence analyses of the protease genes from VB-11,328- and VX-478-resistant variants reveal a sequential accumulation of point mutations, with similar resistance patterns occurring for the two inhibitors [8].

Chemical compound and disease context of AMP

• The baseline phenotypes of wild-type HIV-2 isolates were in the range observed for HIV-1, except for APV and NFV for which a lower degree of sensitivity was seen [2].
• 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB) [9].
• Three HIV-2 isolates were selected for resistance to amprenavir (APV), nelfinavir (NFV), indinavir (IDV), and tipranavir (TPV) in cell culture [2].
• A computational study of the resistance of HIV-1 aspartic protease to the inhibitors ABT-538 and VX-478 and design of new analogues [10].

Biological context of AMP

• Single-dose safety and pharmacokinetics of amprenavir (141W94), a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, in HIV-infected children [11].
• He has founded several successful biotechnology firms, including Vertex Pharmaceuticals in 1989, ARIAD Pharmaceuticals in 1991, and Infinity Pharmaceuticals in 2001 [12].
• The effects of protein binding on the antiviral activity of VX-478 are minor, as expected for a weak drug-protein interaction [13].
• The structure of the two inhibitors 6-Cl-IMP and SAD binding in the IMP and NAD pockets of IMPDH, respectively, gives information for the binding mode of the di-nucleotide cofactor to the enzyme.At Vertex Pharmaceuticals a structure-based drug design program for the design of IMPDH inhibitors was initiated [14].
• The average concentration of 141W94 at 8 and 12 h after single doses of 900 and 1200 mg, respectively, was in excess of 10 times the IC50 [15].

Anatomical context of AMP

• Amprenavir (141W94, VX-478, KVX-478) is metabolized primarily by CYP3A4 (cytochrome P450 3A4) in recombinant systems and human liver microsomes (HLM) [16].
• The most interesting electrode positions for recording the FFR are the Vertex and the mastoid [17].
• It was evident that some of the masking effect that was observed in the Vertex-derived response stemmed from as yet obsure brain stem mechanisms [18].
• The Vertex (Medtronics) system used included longitudinal bars connected to the lateral mas plating system, which was subsequently used to place screws within the keel of the occipital bone [19].

Associations of AMP with other chemical compounds

• Pharmacokinetic sampling was performed on day 8 of each treatment, and samples were analyzed for FPV, amprenavir (APV), LPV, and RTV concentrations by high-performance liquid chromatography-tandem mass spectrometry [20].
• Compound 141W94 (Vertex VX478) (3S)-tetrahydro-3-furyl N-[((S,2R)-3-(4-amino-N-isobutylbenzenesulfonamido)-1-benzyl- 2-hydroxypropyl] carbamate, is a potent HIV-protease inhibitor and is currently undergoing clinical trials [21].
• Urinary symptom scores were significantly lower for the Inlay stent on day 3 than for the Vertex (P = 0.01), Contour (P = 0.05), Endo-Sof (P = 0.03), and Classic (P = 0.02) stents [22].
• The binding of 141W94 to human alpha 1-acid glycoprotein was relatively weak (Kd = 4 microM) and the off-rate for the drug is very fast (> or = 100 s-1) [15].
• Resistant viruses were raised in vitro by passage of HIV-1IIIB in the presence of increasing concentrations of VX-478 and the related hydroxyethylamino sulfonamide inhibitor VB-11,328 [23].

Gene context of AMP

• Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4 [24].
• Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor [25].
• We show that solving the footprint sorting problem requires the solution of the "Minimum Weight Vertex Feedback Set Problem", which is known to be NP-complete and APX-hard [26].
• Quasistatic loading was done at a rate of 2.5 mm/s. Impact loading tests were conducted at a rate of 7.1 to 8.0 m/s. Vertex, parietal, temporal, frontal, and occipital regions were selected as the loading sites [27].
• For the second problem of computing a PPH solution that minimizes the number of distinct haplotypes, we show that the problem is NP-hard using a reduction from Vertex Cover (Garey and Johnson, 1979) [28].

Analytical, diagnostic and therapeutic context of AMP

• Safety and pharmacokinetics of amprenavir (141W94), a human immunodeficiency virus (HIV) type 1 protease inhibitor, following oral administration of single doses to HIV-infected adults [29].
• A test procedure for attenuation correction in SPECT is described and applied to two principally different gamma camera systems (the Siemens Multispect 3 triple-headed system [3HS] and the ADAC Genesys Vertex double-headed system [2HS]) [30].
• Patients undergoing uncomplicated ureteroscopy were randomized to the Bard Inlay, Cook Endo-Sof, Microvasive Contour, Applied Medical Vertex, or Surgitek Classic Double-Pigtail stent [22].
• MATERIAL AND METHODS: The denture liners investigated were Vertex soft (acrylic-based, heat-cured), Coe soft (acrylic-based, auto-cured), Molloplast-B (silicone-based, heat-cured), and Mollosil plus (silicone-based, auto-cured) [31].

References