XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, do... more XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind,
La presente invention concerne l'utilisation d'inhibiteurs de proteine kinases et, plus p... more La presente invention concerne l'utilisation d'inhibiteurs de proteine kinases et, plus particulierement, l'utilisation d'inhibiteurs de la proteine kinase : kinase amino-terminale de c-Jun, de (poly)peptides inhibiteurs de JNK, de peptides chimeriques ou d'acides nucleiques codant pour ceux-ci, ainsi que des compositions pharmaceutiques les contenant, pour le traitement de maladies oculaires inflammatoires non chroniques ou chroniques, telles que des maladies inflammatoire de la paupiere, de la conjonctive, de la cornee, de la sclerotique, du corps vitre, de l'uvee, du corps ciliaire, de la choroide, des os de l'orbite, des glandes lacrymales ou des iris, en particulier la maladie inflammatoire etant choisie parmi l'orgelet, la chalazion, la conjonctivite, la keratite, la sclerite, l'episclerite, l'endophtalmie, la panophtalmie, l'iritis, l'uveite, la cyclite, la chorioidite, le phlegmon orbitaire, la retinite et la myosite du muscle ...
La presente invention concerne l'utilisation d'inhibiteurs des proteines kinase, et en pa... more La presente invention concerne l'utilisation d'inhibiteurs des proteines kinase, et en particulier l'utilisation d'inhibiteurs de la kinase N-terminal c-Jun; de sequences inhibitrices de JNK; de peptides chimeriques; ou l'utilisation d'acides nucleiques codant pour ceux-ci; ainsi que des compositions pharmaceutiques contenant ceux-ci et destinees au traitement de divers troubles ou maladies fortement lies a la voie de signalisation JNK.
La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de la JNK et... more La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de la JNK et leur utilisation dans une methode de traitement therapeutique du corps d'un humain ou d'un animal.
La presente invention concerne l'utilisation d'inhibiteurs de proteine kinase et, plus pr... more La presente invention concerne l'utilisation d'inhibiteurs de proteine kinase et, plus precisement, l'utilisation d'inhibiteurs de la proteine kinase c-Jun, une kinase a extremite amino-terminale, de sequences d'inhibiteurs JNK, de peptides chimeriques ou d'acides nucleiques codant ceux-ci, ainsi que des compositions pharmaceutiques contenant ceux-ci, pour le traitement de diverses maladies ou de divers troubles fortement lies a la signalisation JNK.
Binding fragment of fully human HSV antigen of an antibody that includes a secuenciacon 90% homol... more Binding fragment of fully human HSV antigen of an antibody that includes a secuenciacon 90% homology with SEQ ID NO: 3 or SEQ ID NO: 4 for use in the treatment or diagnosis of ocular unaenfermedad by topical administration.
(Poli) chimeric peptide comprising a (poly) peptide JNK inhibitor for use in treating uveitis, co... more (Poli) chimeric peptide comprising a (poly) peptide JNK inhibitor for use in treating uveitis, comprising or consisting of the (poly) chimeric peptide throughout the sequence of D-amino acids of SEQ ID NO: 11, or a fragment or a variant thereof sharing a sequence identity of at least 90% with the entire sequence of D-amino acids of SEQ ID NO: 11.
La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de JNK et le... more La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de JNK et leur utilisation dans un procede de traitement du corps humain ou animal par therapie.
ABSTRACTHerpes simplex ocular infection is a major cause of corneal blindness. Local antiviral tr... more ABSTRACTHerpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC50and MEC90, respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. Thein vivoefficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, bu...
(+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibi... more (+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that selectively and competitively inhibits P450TB (CYP2C9) in vitro. The potential for kinetic interactions in vivo between fluvastatin and P450TB substrates was therefore investigated in healthy volunteers. Diclofenac (25 mg orally) oxidation was used as a marker of P450TB activity on days 0, 1, and 8 of fluvastatin treatment (40 mg/day). Diclofenac peak concentration (Cmax) increased over time (0.28 [SD, 0.12], 0.38 [0.20], and 0.45 [0.4] mg/L on days 0, 1, and 8, respectively). Oral clearance was reduced on days 1 and 8 (14% and 15%, respectively). A time-dependent decrease in urinary metabolic ratio (MR, 4'-hydroxydiclofenac/diclofenac) was noted (1.07 [0.34], 0.90 [0.23] and 0.70 [0.18] on days 0, 1, and 8, respectively [p < 0.0001]) for the first 4 hours. The interaction was clear in only some individuals; MR reduction was related to baseline MR and it was more pronounced in subjects with a higher baseline MR (p < 0.01). Fluvastatin Cmax (0.18 [0.11] and 0.32 [0.1] mg/L on days 1 and 8, respectively) and area under the curve (0.28 [0.12] and 0.43 [0.15] hr.mg/L on days 1 and 8, respectively; p < 0.001) increased over time. Diclofenac MR reduction was correlated with fluvastatin concentrations. Interactions between fluvastatin and P450TB substrates (phenytoin, oral anticoagulants, oral hypoglycemic agents, and nonsteroidal antiinflammatory drugs) may occur, at least in some patients.
Objective: The affinity of (+)-, (9)- and (±)- fluvastatin, a new synthetic HMG-CoA reductase inh... more Objective: The affinity of (+)-, (9)- and (±)- fluvastatin, a new synthetic HMG-CoA reductase inhibitor developed as a racemate, for specific human P450 monooxygenases in liver microsomes was com-pared with that of the pharmacologically active acidic forms of lovastatin, ...
XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, do... more XG-102 administered to healthy male volunteers as a single intravenous infusion: a randomized, double-blind,
La presente invention concerne l'utilisation d'inhibiteurs de proteine kinases et, plus p... more La presente invention concerne l'utilisation d'inhibiteurs de proteine kinases et, plus particulierement, l'utilisation d'inhibiteurs de la proteine kinase : kinase amino-terminale de c-Jun, de (poly)peptides inhibiteurs de JNK, de peptides chimeriques ou d'acides nucleiques codant pour ceux-ci, ainsi que des compositions pharmaceutiques les contenant, pour le traitement de maladies oculaires inflammatoires non chroniques ou chroniques, telles que des maladies inflammatoire de la paupiere, de la conjonctive, de la cornee, de la sclerotique, du corps vitre, de l'uvee, du corps ciliaire, de la choroide, des os de l'orbite, des glandes lacrymales ou des iris, en particulier la maladie inflammatoire etant choisie parmi l'orgelet, la chalazion, la conjonctivite, la keratite, la sclerite, l'episclerite, l'endophtalmie, la panophtalmie, l'iritis, l'uveite, la cyclite, la chorioidite, le phlegmon orbitaire, la retinite et la myosite du muscle ...
La presente invention concerne l'utilisation d'inhibiteurs des proteines kinase, et en pa... more La presente invention concerne l'utilisation d'inhibiteurs des proteines kinase, et en particulier l'utilisation d'inhibiteurs de la kinase N-terminal c-Jun; de sequences inhibitrices de JNK; de peptides chimeriques; ou l'utilisation d'acides nucleiques codant pour ceux-ci; ainsi que des compositions pharmaceutiques contenant ceux-ci et destinees au traitement de divers troubles ou maladies fortement lies a la voie de signalisation JNK.
La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de la JNK et... more La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de la JNK et leur utilisation dans une methode de traitement therapeutique du corps d'un humain ou d'un animal.
La presente invention concerne l'utilisation d'inhibiteurs de proteine kinase et, plus pr... more La presente invention concerne l'utilisation d'inhibiteurs de proteine kinase et, plus precisement, l'utilisation d'inhibiteurs de la proteine kinase c-Jun, une kinase a extremite amino-terminale, de sequences d'inhibiteurs JNK, de peptides chimeriques ou d'acides nucleiques codant ceux-ci, ainsi que des compositions pharmaceutiques contenant ceux-ci, pour le traitement de diverses maladies ou de divers troubles fortement lies a la signalisation JNK.
Binding fragment of fully human HSV antigen of an antibody that includes a secuenciacon 90% homol... more Binding fragment of fully human HSV antigen of an antibody that includes a secuenciacon 90% homology with SEQ ID NO: 3 or SEQ ID NO: 4 for use in the treatment or diagnosis of ocular unaenfermedad by topical administration.
(Poli) chimeric peptide comprising a (poly) peptide JNK inhibitor for use in treating uveitis, co... more (Poli) chimeric peptide comprising a (poly) peptide JNK inhibitor for use in treating uveitis, comprising or consisting of the (poly) chimeric peptide throughout the sequence of D-amino acids of SEQ ID NO: 11, or a fragment or a variant thereof sharing a sequence identity of at least 90% with the entire sequence of D-amino acids of SEQ ID NO: 11.
La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de JNK et le... more La presente invention concerne l'utilisation de nouvelles molecules inhibitrices de JNK et leur utilisation dans un procede de traitement du corps humain ou animal par therapie.
ABSTRACTHerpes simplex ocular infection is a major cause of corneal blindness. Local antiviral tr... more ABSTRACTHerpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC50and MEC90, respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. Thein vivoefficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, bu...
(+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibi... more (+/-)-Fluvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that selectively and competitively inhibits P450TB (CYP2C9) in vitro. The potential for kinetic interactions in vivo between fluvastatin and P450TB substrates was therefore investigated in healthy volunteers. Diclofenac (25 mg orally) oxidation was used as a marker of P450TB activity on days 0, 1, and 8 of fluvastatin treatment (40 mg/day). Diclofenac peak concentration (Cmax) increased over time (0.28 [SD, 0.12], 0.38 [0.20], and 0.45 [0.4] mg/L on days 0, 1, and 8, respectively). Oral clearance was reduced on days 1 and 8 (14% and 15%, respectively). A time-dependent decrease in urinary metabolic ratio (MR, 4'-hydroxydiclofenac/diclofenac) was noted (1.07 [0.34], 0.90 [0.23] and 0.70 [0.18] on days 0, 1, and 8, respectively [p < 0.0001]) for the first 4 hours. The interaction was clear in only some individuals; MR reduction was related to baseline MR and it was more pronounced in subjects with a higher baseline MR (p < 0.01). Fluvastatin Cmax (0.18 [0.11] and 0.32 [0.1] mg/L on days 1 and 8, respectively) and area under the curve (0.28 [0.12] and 0.43 [0.15] hr.mg/L on days 1 and 8, respectively; p < 0.001) increased over time. Diclofenac MR reduction was correlated with fluvastatin concentrations. Interactions between fluvastatin and P450TB substrates (phenytoin, oral anticoagulants, oral hypoglycemic agents, and nonsteroidal antiinflammatory drugs) may occur, at least in some patients.
Objective: The affinity of (+)-, (9)- and (±)- fluvastatin, a new synthetic HMG-CoA reductase inh... more Objective: The affinity of (+)-, (9)- and (±)- fluvastatin, a new synthetic HMG-CoA reductase inhibitor developed as a racemate, for specific human P450 monooxygenases in liver microsomes was com-pared with that of the pharmacologically active acidic forms of lovastatin, ...
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