Delving into the Latest Updates on TAK-225 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

LTRs x PAF receptor x endothelin receptor

Mechanism

LTRs antagonists(Leukotriene receptor antagonists), PAF receptor antagonists(Platelet activating factor receptor antagonists), endothelin receptor antagonists(Endothelin receptor antagonists)

Therapeutic Areas

Immune System DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Asthma

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization-

Inactive Organization

Takeda Pharmaceutical Co., Ltd.

Drug Highest PhaseDiscontinuedClinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC13H21N5O3S

InChIKeyOQGLMJWGJNCHNA-UHFFFAOYSA-N

CAS Registry152537-59-2

To elucidate whether a newly developed antiallergic drug, the triazolopyridazin derivative TAK-225, alters airway mucociliary clearance and, if so, what the mechanism of action is, we measured mucociliary transport in the rabbit tracheal mucosa ex vivo and ciliary motility of the tracheal epithelium in vitro. Mucociliary transport function was determined by the transport rate of Evans blue dye that had been placed on the mucosal surface above the carina. Oral administration of TAK-225 (0.3-30 mg/kg) increased Evans blue transport toward the larynx in a dose-dependent manner. Addition of TAK-225 caused a rapid and sustained increase in the ciliary beat frequency of tracheal epithelium, as assessed by photoelectric method; the maximal increase from the base-line value was 25.1 +/- 4.6% (P < .01), and the concentration required to produce a half-maximal effect (EC50) was 3.1 +/- 0.8 x 10(-7) M. This effect was greatly attenuated by pretreatment with the cAMP antagonist adenosine 3',5'-cyclic monophosphorothioate, but not by Ca++-free medium containing ethylene glycol-bis [3-aminoethyl ether] N,N,N',N'-tetraacetic acid and [1,2-bis(2)aminophenoxy]ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. Incubation of tracheal epithelium with TAK-225 increased intracellular cAMP contents in a concentration-dependent manner. These results suggest that TAK-225 enhances airway mucociliary clearance probably through cAMP-mediated stimulation of ciliary motility of airway epithelium.

100 Deals associated with TAK-225

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