Stable_integration_of_a_xenobiotic_receptor_promoter-reporter_DNA_construct_into_human_liver_cell_line_for_evaluating_the_drugs_by_high_throughput_screening
The_Pregnane_&_Xenobiotic_Receptor_(PXR;_NR1I2),_a_member_of_the_nuclear_receptor_super-family,_is_a_well-known_xenobiotic_sensing_receptor._The_highly_promiscuous_nature_of_PXR_allows_it_to_interact_with_a_wide_range_of_structurally_diverse_chemicals._Ligand-activated_PXR_up-regulates_the_expression_of_drug-metabolizing_enzymes_and_drug_transporters_to_protect_the_cell_from_chemical_insults._However,_the_physiological_importance_of_PXR_extends_beyond_xenobiotic_protection._Most_importantly,_the_regulation_of_drug-metabolizing_enzymes_by_PXR_may_result_in_clinical_drug–drug_interactions,_in_which_one_drug_accelerates_the_metabolism_of_a_second_medication_and_may_change_or_cause_adverse_results._This_not_only_reduces_the_therapeutic_efficacy_of_many_drugs_on_combination_therapy_but_may_also_cause_life-threatening_situations._Therefore,_the_complete_evaluation_and_safety_assessment_of_any_drug_(clinical_or_herbal)_which_is_to_be_administered_is_indispensable. _Although_there_are_various_methods,_which_are_available_to_assess_the_pharmacological_properties_by_drug_screening,_but_due_to_their_high_cost,_lengthy_experimental_duration_offers_only_limited_use.In_this_context,_a_cell_based_screening_approach_for_evaluating_the_therapeutic_value_and_safety_assessment_of_clinical_or_herbal_drugs,_xenobiotics_and_endobiotics_are_capable_of_being_addressed_at_two_main_levels_by_engaging_(i)_PXR_protein_based_or_(ii)_PXR-promoter_based_transcription_assays:
Cell_based_screening_protocol_for_'Level_1'_is_already_available_(22,_EPO-_WO2004016759,_USPTO-_20040077080)_but_cell_based_screening_protocol_for_'Level_2'_is_now_possible_here._The_present_claim_relates_to_achievement_of_'Level_2'_screening_for_drugs,_xenobiotics_and_endobiotics._This_screening_is_achieved_with_the_use_of_PXR-promoter-reporter_construct_that_we_have_developed_and_stably_integrated_into_a_human_liver_cell_line._Additional_advantages_of_this_stable_PXR-promoter-reporter_cell_line_would_be_in_its_ability_to_predict_potential_drug-drug_interactions,_to_identify_PXR_regulatory_proteins,_and_also_to_evaluate_the_modulatory_effects_of_an_experimental_molecule_on_PXR_promoter_activity.
In_conclusion,_the_present_invention_relates_to_a_stably_integrated_PXR_promoter-reporter_construct-cell_line_comprising_PXR_promoter_of_-1096_to_+43_region_which_is_capable_of_assessing_drug's_capability_to_bind_and_induce_PXR-promoter_on_its_administration,_and_hence,_is_capable_of_indirectly_influencing_the_protein_level_of_the_PXR-promoter_on_its_administration_so_as_to_avoid_failure_of_combination_therapy._In_one_embodiment,_it_relates_to_a_method_of_preparation_of_stably_integrated_PXR_promoter-reporter_construct-cell_line._In_another_embodiment,_it_relates_to_a_PXR_promoter_and_to_a_PXR-promoter-reporter_construct.
Interested_parties_who_want_to_bid_for_the_technology_may_submit_their_bid_in_the_office_of _Chairperson,_Intellectual_Property_Management_cell,_Room_No.117,_Administration_Block,_Jawaharlal_Nehru_University,_New_Delhi-110067,_so_as_to_reach_this_office on_or_before_20th_August,_2012._For_any_further_clarification_and_seeking_appointment_the_interested_parties_can_contact: Dr._Rakesh_K._Tyagi,_Special_Centre_for_Molecular_Medicine,_Jawaharlal_Nehru_University,_New_Delhi_-110067 by e.mail: rktyagi@yahoo.com
Include_Pharmaceutical_companies_and_industries_industries_involved_in_toxicological_evaluation_of_xenobiotics_(clinical_drugs,_herbal_drugs_pesticides_etc)_and_endobiotic_metabolites.