Pharmacokinetics and metabolism of HOE 077

Kellner, H. M.; Volz, M; Baader, E.; Kürzel, Gert Ulrich; Eckert, Hans-Georg

doi:10.1016/0168-8278(91)90008-y

Cited by 10 publications

(9 citation statements)

References 8 publications

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“…The K 2 and K 3 values are very close to those of ETAM and DEATAM. Instead, the major differences between TAMmeg and the other neutral-sidechain ligands lie in the first complexation equilibrium constant logβ 110 (at least 0.6 log units greater than logβ 110 for ETAM (12) or DEATAM (11)) and in the first proton association constant logβ 011 (at least 0.3 log units lower than logβ 011 for ETAM or DEATAM).…”

Section: Solution Thermodynamicsmentioning

confidence: 99%

“…The 2-methoxyethylamide moiety should be compatible with the goal of limited ligand toxicity based on previous investigations in which a similar pyridine-based compound containing 2-methoxyethylamide units (considered for an unrelated pharmaceutical application) was found to have an acceptable toxicity profile. 11,12 This work details the synthesis of TAMmeg and structural and thermodynamic studies of the ligand and its iron complex. The solid state structures of the ligand, its benzyl-protected precursor, and its iron complex were characterized by X-ray diffraction.…”

Section: Introductionmentioning

confidence: 99%

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A Bidentate Terephthalamide Ligand, TAMmeg, as an Entry into Terephthalamide-Containing Therapeutic Iron Chelating Agents

Jurchen

Raymond

2006

Inorg. Chem.

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A new bidentate 2,3-dihydroxyterephthalamide ligand, 2,3-dihydroxy-N,N′-bis(2-methoxyethyl)terephthalamide (TAMmeg), has been prepared. The ligand, its synthetic precursor 2,3-bis(benzyloxy)-N, N′-bis(2-methoxy-ethyl)-terephthalamide (BnTAMmeg), and its iron complex have been structurally characterized by X-ray diffraction. BnTAMmeg crystallizes in the monoclinic space group P2 1 /n with cell parameters a = 14.4976 (14)

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Section: Solution Thermodynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Bidentate Terephthalamide Ligand, TAMmeg, as an Entry into Terephthalamide-Containing Therapeutic Iron Chelating Agents

Jurchen

Raymond

2006

Inorg. Chem.

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“…Berenil is a synthetic drug that is effective against animal trypanosomiasis [ 1,2]. The pharmacological effect of berenil in vivo has been related [l] to its preference for kinetoplast DNA (kDNA).…”

Section: Introductionmentioning

confidence: 99%

Berenil acts as a poison of eukaryotic topoisomerase II

Portugal

1994

FEBS Letters

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The ability of the anti-trypanosomal drug berenil to interfere with the activities of eukaryotic type II topoisomerases is evaluated using two different types of reactions catalyzed by the enzyme: the relaxation of naturally supercoiled DNA and the decatenation of kinetoplast DNA (kDNA). The results indicate that berenil acts as an inhibitor of the catalytic activity, but the inhibiting ability appears to be smaller than for other minor-groove binding ligands.

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“…HOE 077 has been shown to be effec tive in vitro [6,24] and in vivo [19,20] in preventing fibrogenesis. Pharmacokinetic studies of the drug have shown a distribution of the inhibitor in all organs includ ing the pancreas and a biphasic elimination with half-lives of 2 and 19 h [25]. We have employed the inhibitor HOE 077 in the cerulein pancreatitis model in an attempt to modify collagen biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Failure of a Prolyl 4-Hydroxylase Inhibitor to Alter Extracellular Matrix Deposition during Experimental Pancreatitis

Weidenbach

Lerch²,

Turi³

et al. 1997

Digestion

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In chronic pancreatitis the exocrine pancreatic tissue is replaced by extracellular matrix deposits from fibroblasts. We have stimulated fibrogenesis in the pancreas by inducing a single episode of cerulein pancreatitis (10 μg/kg/h for 12 h). We have used a spectrophotometrical assay to measure the tissue hydroxyproline content and immunohistochemistry to study the transient deposition of extracellular matrix in the pancreas. We have investigated whether a potent prolyl 4-hydroxylase inhibitor (HOE-077) can influence the deposition of extracellular matrix in the pancreas. Three days after the induction of the pancreatitis we found the maximum increase in pancreatic hydroxyproline content (by 63%), the maximum decrease in total protein content and amylase activity (by -39 and -86%, respectively), as well as a significant increase in DNA content and the deposition of interstitial collagen fibers on electron microscopy. By immunohistochemistry the largest expansion of extracellular matrix components was found for fibronectin. HOE 077, regardless of the concentration administered, failed to affect any of these parameters. We conclude that the induction of a single episode of cerulein pancreatitis and the serial determination of pancreatic hydroxyproline content represents a simple method to induce and monitor experimental fibrogenesis in the pancreas. Prolyl 4-hydroxylase inhibition did not affect the course of extracellular matrix deposition in the pancreas.

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Pharmacokinetics and metabolism of HOE 077

Cited by 10 publications

References 8 publications

A Bidentate Terephthalamide Ligand, TAMmeg, as an Entry into Terephthalamide-Containing Therapeutic Iron Chelating Agents

A Bidentate Terephthalamide Ligand, TAMmeg, as an Entry into Terephthalamide-Containing Therapeutic Iron Chelating Agents

Berenil acts as a poison of eukaryotic topoisomerase II

Failure of a Prolyl 4-Hydroxylase Inhibitor to Alter Extracellular Matrix Deposition during Experimental Pancreatitis

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