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Antipsoriasis Agent

The Experts below are selected from a list of 24 Experts worldwide ranked by ideXlab platform

Y. Nancy Wong – One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic characterization of a natural product–inspired novel MEK1 inhibitor E6201 in preclinical species
    Cancer Chemotherapy and Pharmacology, 2012
    Co-Authors: Vipul Kumar, Philip Saxton, Edgar Schuck, Robert D. Pelletier, Nadia Farah, Christopher Rowbottom, Belinda M. King, Zhi-yi Zhang, Krista B. Condon, Y. Nancy Wong

    Abstract:

    Purpose E6201 is a natural product–inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase-1 (MEK1) and other kinases and is currently under development as an anticancer (parenteral administration) and Antipsoriasis Agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201. Methods In vitro metabolism studies for CYP induction and CYP inhibition were conducted using human hepatocytes and microsomes, respectively. Metabolic stability using microsomes and protein-binding studies using pooled plasma were performed for mice, rats, dogs, and human. Pharmacokinetics of E6201 and its isomeric metabolite, ER-813010, in mice, rats, and dogs was determined following single IV administration of E6201 at three dose levels. Bioanalysis was performed using LC/MS/MS. Pharmacokinetic parameters were determined using non-compartmental analysis, and allometric scaling with a two-compartment model was used to predict E6201 pharmacokinetics in humans. Results E6201 showed high plasma protein binding (>95%), and metabolic stability half-life ranged from 36 to 89 min across species. In vitro CYP inhibition (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A) and CYP induction (CYP1A, 3A, 2C9, and 2C19) suggested no inhibitory or induction effect on the tested human CYPs up to 10 μM of E6201. Pharmacokinetics of E6201 in mice, rats, and dogs was characterized by mean clearance ranging from 3.45 to 10.92 L/h/kg, distribution volume ranging from 0.63 to 13.09 L/kg, and elimination half-life ranging from 0.4 to 1.6 h. ER-813010 was detected in all species with metabolite to parent exposure ratio (AUC_R) ranging from 3.1 to 33.4% and exhibited fast elimination (

Vipul Kumar – One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic characterization of a natural product–inspired novel MEK1 inhibitor E6201 in preclinical species
    Cancer Chemotherapy and Pharmacology, 2012
    Co-Authors: Vipul Kumar, Philip Saxton, Edgar Schuck, Robert D. Pelletier, Nadia Farah, Christopher Rowbottom, Belinda M. King, Zhi-yi Zhang, Krista B. Condon, Y. Nancy Wong

    Abstract:

    Purpose E6201 is a natural product–inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase-1 (MEK1) and other kinases and is currently under development as an anticancer (parenteral administration) and Antipsoriasis Agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201. Methods In vitro metabolism studies for CYP induction and CYP inhibition were conducted using human hepatocytes and microsomes, respectively. Metabolic stability using microsomes and protein-binding studies using pooled plasma were performed for mice, rats, dogs, and human. Pharmacokinetics of E6201 and its isomeric metabolite, ER-813010, in mice, rats, and dogs was determined following single IV administration of E6201 at three dose levels. Bioanalysis was performed using LC/MS/MS. Pharmacokinetic parameters were determined using non-compartmental analysis, and allometric scaling with a two-compartment model was used to predict E6201 pharmacokinetics in humans. Results E6201 showed high plasma protein binding (>95%), and metabolic stability half-life ranged from 36 to 89 min across species. In vitro CYP inhibition (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A) and CYP induction (CYP1A, 3A, 2C9, and 2C19) suggested no inhibitory or induction effect on the tested human CYPs up to 10 μM of E6201. Pharmacokinetics of E6201 in mice, rats, and dogs was characterized by mean clearance ranging from 3.45 to 10.92 L/h/kg, distribution volume ranging from 0.63 to 13.09 L/kg, and elimination half-life ranging from 0.4 to 1.6 h. ER-813010 was detected in all species with metabolite to parent exposure ratio (AUC_R) ranging from 3.1 to 33.4% and exhibited fast elimination (

  • Pharmacokinetic characterization of a natural product–inspired novel MEK1 inhibitor E6201 in preclinical species
    Cancer Chemotherapy and Pharmacology, 2011
    Co-Authors: Vipul Kumar, Edgar Schuck, Robert D. Pelletier, Nadia Farah, Krista Condon, Christopher Rowbottom, Belinda M. King, Zhi-yi Zhang, Philip Saxton

    Abstract:

    Purpose
    E6201 is a natural product–inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase-1 (MEK1) and other kinases and is currently under development as an anticancer (parenteral administration) and Antipsoriasis Agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201.

Philip Saxton – One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic characterization of a natural product–inspired novel MEK1 inhibitor E6201 in preclinical species
    Cancer Chemotherapy and Pharmacology, 2012
    Co-Authors: Vipul Kumar, Philip Saxton, Edgar Schuck, Robert D. Pelletier, Nadia Farah, Christopher Rowbottom, Belinda M. King, Zhi-yi Zhang, Krista B. Condon, Y. Nancy Wong

    Abstract:

    Purpose E6201 is a natural product–inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase-1 (MEK1) and other kinases and is currently under development as an anticancer (parenteral administration) and Antipsoriasis Agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201. Methods In vitro metabolism studies for CYP induction and CYP inhibition were conducted using human hepatocytes and microsomes, respectively. Metabolic stability using microsomes and protein-binding studies using pooled plasma were performed for mice, rats, dogs, and human. Pharmacokinetics of E6201 and its isomeric metabolite, ER-813010, in mice, rats, and dogs was determined following single IV administration of E6201 at three dose levels. Bioanalysis was performed using LC/MS/MS. Pharmacokinetic parameters were determined using non-compartmental analysis, and allometric scaling with a two-compartment model was used to predict E6201 pharmacokinetics in humans. Results E6201 showed high plasma protein binding (>95%), and metabolic stability half-life ranged from 36 to 89 min across species. In vitro CYP inhibition (CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A) and CYP induction (CYP1A, 3A, 2C9, and 2C19) suggested no inhibitory or induction effect on the tested human CYPs up to 10 μM of E6201. Pharmacokinetics of E6201 in mice, rats, and dogs was characterized by mean clearance ranging from 3.45 to 10.92 L/h/kg, distribution volume ranging from 0.63 to 13.09 L/kg, and elimination half-life ranging from 0.4 to 1.6 h. ER-813010 was detected in all species with metabolite to parent exposure ratio (AUC_R) ranging from 3.1 to 33.4% and exhibited fast elimination (

  • Pharmacokinetic characterization of a natural product–inspired novel MEK1 inhibitor E6201 in preclinical species
    Cancer Chemotherapy and Pharmacology, 2011
    Co-Authors: Vipul Kumar, Edgar Schuck, Robert D. Pelletier, Nadia Farah, Krista Condon, Christopher Rowbottom, Belinda M. King, Zhi-yi Zhang, Philip Saxton

    Abstract:

    Purpose
    E6201 is a natural product–inspired novel inhibitor of mitogen-activated protein kinase/extracellular signal–regulated kinase kinase-1 (MEK1) and other kinases and is currently under development as an anticancer (parenteral administration) and Antipsoriasis Agent (topical application). In vitro and in vivo preclinical studies were performed to characterize the pharmacokinetics of E6201. Allometric scaling was applied to predict human pharmacokinetics of E6201.