PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 15866340-9 2005 This finding is particularly important in the development of a novel CPA/methotrexate-alpha-peptide system in solid tumor chemotherapy. Methotrexate 73-85 carboxypeptidase A1 Homo sapiens 69-72 10022548-1 1999 In an effort to develop a gene-dependent enzyme/prodrug therapy (GDEPT) for tumor-specific delivery of methotrexate (MTX) we have chosen to construct mutant forms of carboxypeptidase A1 (CPA) that circumvent the requirement for trypsin-dependent activation. Methotrexate 103-115 carboxypeptidase A1 Homo sapiens 166-185 10022548-1 1999 In an effort to develop a gene-dependent enzyme/prodrug therapy (GDEPT) for tumor-specific delivery of methotrexate (MTX) we have chosen to construct mutant forms of carboxypeptidase A1 (CPA) that circumvent the requirement for trypsin-dependent activation. Methotrexate 117-120 carboxypeptidase A1 Homo sapiens 166-185 1731945-8 1992 This potentiation of MTX-Ala cytotoxicity by conjugate-bound CP-A, which was at least 30-fold greater than that produced by a comparable amount of free enzyme, is attributed to enhanced effectiveness of MTX generated at the cell surface as opposed to the surrounding medium. Methotrexate 21-24 carboxypeptidase A1 Homo sapiens 61-65 9188478-7 1997 We report here the first test of this concept using the human enzyme carboxypeptidase A1 (hCPA1) and prodrugs of methotrexate (MTX). Methotrexate 127-130 carboxypeptidase A1 Homo sapiens 69-88 9188478-16 1997 The results showed that the targeted ING-1:hCPA1-T268G conjugate produced excellent activation of the MTX prodrugs to kill HT-29 cells as efficiently as MTX itself. Methotrexate 102-105 carboxypeptidase A1 Homo sapiens 43-48 9188478-16 1997 The results showed that the targeted ING-1:hCPA1-T268G conjugate produced excellent activation of the MTX prodrugs to kill HT-29 cells as efficiently as MTX itself. Methotrexate 153-156 carboxypeptidase A1 Homo sapiens 43-48 8806703-8 1996 The kcat/Km values for MTX-Phe were 440,000 and 90,000 M-1 s-1 for hCPA1 and hCPA2, respectively, and for MTX-naphthylAla these values were 1400 and 1,400,000 M-1 s-1 for hCPA1 and hCPA2, respectively. Methotrexate 23-26 carboxypeptidase A1 Homo sapiens 67-72 8806703-8 1996 The kcat/Km values for MTX-Phe were 440,000 and 90,000 M-1 s-1 for hCPA1 and hCPA2, respectively, and for MTX-naphthylAla these values were 1400 and 1,400,000 M-1 s-1 for hCPA1 and hCPA2, respectively. Methotrexate 23-26 carboxypeptidase A1 Homo sapiens 171-176 7834611-4 1995 When the lung tumor cells were treated with CPA conjugated to KS1/4 (a mAb targeted to these cells) and excess conjugate removed by extensive washing, the ID50 for MTX-Phe improved from 2.2 x 10(-6) M (no enzyme present) to 6.3 x 10(-8) M; the latter value was comparable to that of the parent drug MTX (4.5 x 10(-8) M). Methotrexate 299-302 carboxypeptidase A1 Homo sapiens 44-47 7834611-6 1995 The present results demonstrate that, for use in conjunction with CPA-mAb conjugates, the alpha-phenylalanine derivative is the optimal prodrug form of MTX (and probably other antifols that contain the glutamate moiety). Methotrexate 152-155 carboxypeptidase A1 Homo sapiens 66-69 21559659-3 1994 An enzymatic assay was then developed using CZE for monitoring the hydrolysis of the MTX-alpha-peptides by bovine pancreatic carboxypeptidase A (CP-A) leading to the release of free MTX. Methotrexate 85-88 carboxypeptidase A1 Homo sapiens 145-149 9893962-0 1999 Antibody-directed enzyme prodrug therapy with the T268G mutant of human carboxypeptidase A1: in vitro and in vivo studies with prodrugs of methotrexate and the thymidylate synthase inhibitors GW1031 and GW1843. Methotrexate 139-151 carboxypeptidase A1 Homo sapiens 72-91 9893962-2 1999 Our approach to this technology has been to design a mutant of human carboxypeptidase A (hCPA1-T268G) which is capable of hydrolyzing in vivo stable prodrugs of MTX and targeting this enzyme to tumors on an Ep-CAM1-specific antibody, ING1. Methotrexate 161-164 carboxypeptidase A1 Homo sapiens 89-94 7834611-0 1995 Methotrexate-alpha-phenylalanine: optimization of methotrexate prodrug for activation by carboxypeptidase A-monoclonal antibody conjugate. Methotrexate 50-62 carboxypeptidase A1 Homo sapiens 89-107 7834611-2 1995 Production of MTX from MTX-Phe, catalyzed by bovine pancreas carboxypeptidase A (CPA), was 250-fold faster than the corresponding reaction involving methotrexate-alpha-alanine, previously the best MTX peptide substrate for the enzyme. Methotrexate 14-17 carboxypeptidase A1 Homo sapiens 61-79 7834611-2 1995 Production of MTX from MTX-Phe, catalyzed by bovine pancreas carboxypeptidase A (CPA), was 250-fold faster than the corresponding reaction involving methotrexate-alpha-alanine, previously the best MTX peptide substrate for the enzyme. Methotrexate 14-17 carboxypeptidase A1 Homo sapiens 81-84 7834611-2 1995 Production of MTX from MTX-Phe, catalyzed by bovine pancreas carboxypeptidase A (CPA), was 250-fold faster than the corresponding reaction involving methotrexate-alpha-alanine, previously the best MTX peptide substrate for the enzyme. Methotrexate 23-26 carboxypeptidase A1 Homo sapiens 61-79 7834611-2 1995 Production of MTX from MTX-Phe, catalyzed by bovine pancreas carboxypeptidase A (CPA), was 250-fold faster than the corresponding reaction involving methotrexate-alpha-alanine, previously the best MTX peptide substrate for the enzyme. Methotrexate 23-26 carboxypeptidase A1 Homo sapiens 81-84 7834611-3 1995 The amount of CPA required to make MTX-Phe equitoxic with MTX, when tested against UCLA-P3 human lung adenocarcinoma cells in vitro, was more than 10-fold lower than that required to achieve the same result with MTX-alpha-alanine. Methotrexate 35-38 carboxypeptidase A1 Homo sapiens 14-17 7834611-4 1995 When the lung tumor cells were treated with CPA conjugated to KS1/4 (a mAb targeted to these cells) and excess conjugate removed by extensive washing, the ID50 for MTX-Phe improved from 2.2 x 10(-6) M (no enzyme present) to 6.3 x 10(-8) M; the latter value was comparable to that of the parent drug MTX (4.5 x 10(-8) M). Methotrexate 164-167 carboxypeptidase A1 Homo sapiens 44-47