Ahn S.O.,Discovery Research Center |
Ohtomo S.,Chugai Pharmaceutical Co. |
Kiyokawa J.,Chugai Pharmaceutical Co. |
Nakagawa T.,Chugai Pharmaceutical Co. |
And 7 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2016
Urate-lowering therapy is indispensable for the treatment of gout, but available drugs do not control serum urate levels tightly enough. Although the uricosurics benzbromarone and probenecid inhibit a urate reabsorption transporter known as renal urate transporter 1 (URAT1) and thus lower serum urate levels, they also inhibit other transporters responsible for secretion of urate into urine, which suggests that inhibiting URAT1 selectively would lower serum urate more effectively. We identified a novel potent and selective URAT1 inhibitor, UR-1102, and compared its efficacy with benzbromarone in vitro and in vivo. In human embryonic kidney (HEK)293 cells overexpressing URAT1, organic anion transporter 1(OAT1), and OAT3, benzbromarone inhibited all transporters similarly, whereas UR-1102 inhibited URAT1 comparably to benzbromarone but inhibited OAT1 and OAT3 quite modestly. UR-1102 at 3-30 mg/kg or benzbromarone at 3-100 mg/kg was administered orally once a day for 3 consecutive days to tufted capuchin monkeys, whose low uricase activity causes a high plasma urate level. When compared with the same dosage of benzbromarone, UR-1102 showed a better pharmacokinetic profile, increased the fractional excretion of urinary uric acid, and reduced plasma uric acid more effectively. Moreover, the maximum efficacy of UR-1102 was twice that of benzbromarone, suggesting that selective inhibition of URAT1 is effective. Additionally UR-1102 showed lower in vitro potential for mechanisms causing the hepatotoxicity induced by benzbromarone. These results indicate that UR-1102 achieves strong uricosuric effects by selectively inhibiting URAT1 over OAT1 and OAT3 in monkeys, and could be a novel therapeutic option for patients with gout or hyperuricemia. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.
Bio Synectics Inc. and JW Pharmaceutical Corporation | Date: 2010-09-20
The present invention relates to a nanoparticle of oxaliplatin, which is a water-soluble active substance, a pharmaceutical composition containing the same, and a method for preparing an orally administrable oxaliplatin nanoparticle by emulsifying a lipid mixture solution wherein a solid lipid and a surfactant are mixed in an aqueous mixture solution wherein oxaliplatin and a specific cosolvent are mixed and then removing the solid lipid and the cosolvent using a supercritical fluid gas. By providing oxaliplatin, which is currently available only in injection form for parenteral administration, in the form of a nanoparticle, the present invention allows for the development of orally administrable oxaliplatin which is stable against gastric acid and has improved bioavailability, thereby improving patient compliance through avoiding the inconvenience of injection and greatly reducing medical cost. Since the oxaliplatin nanoparticle can be prepared economically using a relatively inexpensive supercritical fluid producing facility, it can be prepared via a simple process with high yield in commercial scale.
Jw Pharmaceutical Corporation | Date: 2015-04-03
Acetaminophen for relief of pain; Cough syrups; Cough treatment preparations; Pharmaceutical agents affecting metabolism; Pharmaceutical agents affecting sensory organs; Pharmaceutical preparations acting on the central nervous system; Vitamin preparations; Pharmaceutical preparations for the treatment of respiratory organs.
Oh S.-W.,JW Pharmaceutical Corporation |
Lee J.B.,McMaster University |
Kim B.,Ewha Womans University |
Jeon S.,Ewha Womans University |
And 6 more authors.
Archives of Pharmacal Research | Year: 2012
Embryonic stem (ES) cells may be used as an alternative source of functionally intact cardiomyocytes for ischemic heart disease. Several natural and synthetic small molecules have been identified as useful tools for controlling and manipulating stem cell renewal and differentiation. Currently, there is an urgent requirement for novel small molecules that specifically induce differentiation of stem cells into cardiomyocytes. To identify compounds that promote cardiomyogenesis of stem cells, cell-based screening of a peptidomimetic small-molecule library was carried out. A series of β-turn peptidomimetic compounds, including CW209E, increased the expression of α-MHC promoter-driven enhanced green fluorescent protein (EGFP) and ratio of beating embryoid bodies (EBs) without inducing cytotoxicity in mouse embryonic stem cells. CW209E also increased the number of beating EBs in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Thus, this chemical compound should be useful for elucidation of the molecular pathway of cardiogenesis and generation of cardiomyocytes ex vivo, which can be further applied for experimental or clinical cell therapy for ischemic heart diseases. © 2012 The Pharmaceutical Society of Korea and Springer Science+Business Media Dordrecht.
Jw Pharmaceutical Corporation | Date: 2011-10-14
This invention relates to novel compounds of reverse-turn mimetics, having pyrazino-triazinone as a basic framework, and a method of preparing the same, and the use thereof to treat diseases such as cancer, in particular, acute myeloid leukemia.