Hsu W.-T.,National Taiwan University |
Hsu W.-T.,National Health Research Institute |
Jui H.-Y.,National Taiwan University Hospital |
Huang Y.-H.,TaiGen Biotechnology Co. |
And 9 more authors.
Cell Transplantation | Year: 2015
Interaction between chemokine stromal cell-derived factor 1 and the CXC chemokine receptor 4 (CXCR4) governs the sequestration and mobilization of bone marrow stem cells. We investigated the therapeutic potential of TG-0054, a novel CXCR4 antagonist, in attenuating cardiac dysfunction after myocardial infarction (MI). In miniature pigs (minipigs), TG-0054 mobilized CD34+CXCR4+, CD133+CXCR4+, and CD271+CXCR4+ cells into peripheral circulation. After isolation and expansion, TG-0054-mobilized CD271+ cells were proved to be mesenchymal stem cells (designated CD271-MSCs) since they had trilineage differentiation potential, surface markers of MSCs, and immunosuppressive effects on allogeneic lymphocyte proliferation. MI was induced in 22 minipigs using balloon occlusion of the left anterior descending coronary artery, followed by intravenous injections of 2.85 mg/kg of TG-0054 or saline at 3 days and 7 days post-MI. Serial MRI analyses revealed that TG-0054 treatment prevented left ventricular (LV) dysfunction at 12 weeks after MI (change of LV ejection fraction from baseline, −1.0 ± 6.2% in the TG-0054 group versus −7.9 ± 5.8% in the controls). The preserved cardiac function was accompanied by a significant decrease in the myocardial expression of TNF-α, IL-1β, and IL-6 at 7 days post-MI. Moreover, the plasma levels of TNF-α, IL-1β, and IL-6 were persistently suppressed by the TG-0054 treatment. Infusion of TG-0054-mobilized CD271-MSCs reduced both myocardial and plasma cytokine levels in a pattern, which is temporally correlated with TG-0054 treatment. This study demonstrated that TG-0054 improves the impaired LV contractility following MI, at least in part, by mobilizing MSCs to attenuate the postinfarction inflammation. This insight may facilitate exploring novel stem cell-based therapy for treating post-MI heart failure. © 2015 Cognizant Comm. Corp.
Lin H.-C.,National Chiao Tung University |
Lin H.-C.,China Medical University at Taichung |
Lin C.-C.,National Chiao Tung University |
Lin C.-C.,TaiGen Biotechnology Co. |
And 2 more authors.
Tetrahedron | Year: 2011
Ozonolysis of bis-endo-diacylbicyclo[2.2.1]heptenes 3a-d at -78 °C in dichloromethane-methanol gave the hydroperoxides 6a-d in 70-80% yields. Ozonolysis of bis-endo-diacetylbicyclo[2.2.2]octene 15 and bis-endo-diacetyl-7- oxabicyclo-[2.2.1]heptene 16 under the same reaction conditions gave the hydroperoxides 17 and 18, respectively. The intramolecular sequential nucleophilic addition of the carbonyl groups to the carbonyl oxide group was observed for the first time and was found to be faster than the intermolecular nucleophilic addition of a methanol molecule to the carbonyl oxide group. Ozonolysis of compound 23 in CH2Cl2-MeOH at -78 °C followed by reduction with Me2S gave compounds 24 and 25, in which the stereochemistry of the methoxyl groups was determined by X-ray analysis. © 2011 Elsevier Ltd. All rights reserved.
News Article | October 30, 2016
TAIPEI, Taiwan, October 30, 2016 /PRNewswire/ -- TaiGen Biotechnology Co., Ltd. ("TaiGen") announced today that its wholly owned subsidiary, TaiGen Biopharmaceuticals Co. (Beijing), Ltd. has signed an agreement with YiChang HEC ChangJiang Pharmaceutical Co., Ltd ("HEC") to establish a new company ("Newco") in mainland China for the joint development, manufacturing, and commercialization of direct-acting antiviral agents (DAAs) for all-oral interferon-free treatments of chronic hepatitis C virus (HCV) infection in the Greater China region (mainland China, Taiwan, Hong Kong, and Macau). The Newco will be the first of its kind in a cross-strait partnership in the pharmaceutical industry. It also formalized the collaboration in the MOU signed in February 2016. Under the terms of the Agreement, the Newco will be capitalized at RMB 680 million (US$102 million). TaiGen will use the intellectual property rights of furaprevir (TG-2349) in Greater China as contribution in kind for 49% equity in the Newco. HEC will use the intellectual property rights of yimitasvir (DAG-181) in Greater China as contribution in kind and an additional cash investment in exchange for 51% equity in the Newco. TaiGen will be responsible for research, clinical development, and registration and HEC will be responsible for operation, manufacturing, sales and marketing of HCV treatment based on furaprevir and yimitasvir. Upon the establishment of the Newco, TaiGen and HEC will execute a separate share transfer agreement where TaiGen will receive from HEC a sum between US$20 to 40 million based on the Phase 2 clinical trial results. After the share transfer is complete, TaiGen will hold 40% equity and HEC 60% equity in the Newco. TaiGen's furaprevir, a HCV NS3 protease inhibitor, is completing a Phase 2 clinical trial in HCV genotype 1b patients in Taiwan. HEC's yimitasvir, an NS5a inhibitor, has completed in Phase 1 trial in mainland China. Both furaprevir and yimitasvir are DAAs, classified as Class 1.1 by CFDA, and were discovered and developed in-house by TaiGen and HEC respectively. According to the estimates from WHO and IMS, the number of HCV patients in mainland China ranges from 10-40 million making it the largest HCV market in the world. At present, less than 10% of the HCV patients are receiving treatment. This is due to low awareness of the disease and the severe and intolerable side effects of interferon-based treatment. Although all-oral interferon-free DAA-based HCV regiments are already available in many countries, none of these are currently approved in mainland China. To expedite the approval and availability of the revolutionary treatment, China's Center for Drug Evaluation has begun to grant priority review status to HCV drugs in development. Furaprevir was granted priority review in April 2016 and TaiGen is the only Taiwanese firm among the seven companies that receive priority review. Dr. Ming-Chu Hsu, Chairman and CEO of TaiGen said "Mainland China remains the largest untapped HCV market. We are confident that combining both drugs and company expertise will accelerate the development of our DAA regiment and become a formidable competitor in the Greater China HCV market. This partnership with HEC will be another significant milestone in TaiGen's history and take TaiGen to the next level." Mr. Show-Chung Ho, Chairman of TaiGen's Steering Committee commented, "TaiGen has a successful track record in clinical development and obtaining market approval in mainland China. HEC has the integrated marketing and distribution channels. The synergy that the two companies and their drugs create will bring tremendous benefits to the HCV patients in this region." About YiChang HEC ChangJiang Pharmaceutical YiChang HEC ChangJiang Pharmaceutical, a public listed company in the Hong Kong Stock Exchange (1558.HK), focuses on the development, manufacturing and sales of pharmaceutical products in viral infections, endocrine, metabolic and cardiovascular diseases. HEC's leading product, Kewei (oseltamivir phosphate) is the No. 1 selling influenza drug in China from 2013 to 2015. YiChang HEC is part of HEC Pharmaceutical Group. Its products are exported overseas to the US, Japan, Germany and Australia. HEC Pharmaceutical Group is part of the HEC Group with businesses in materials, healthcare, cosmetics, tourism, and hospitality. About TaiGen Biotechnology TaiGen Biotechnology, a public listed company in Taipei Exchange (4157.TWO), is a leading research-based biotechnology company in Taiwan. TaiGen's pipeline includes other in-house discovered and developed new chemical entities: Taigexyn®, a novel antibiotic, is one of the first NCEs developed by a Taiwanese company that received market approval and launched in Taiwan and mainland China. Burixafor, a chemokine receptor antagonist, is in Phase 2 clinical development for stem cell transplantation and chemosensitization in the US and mainland China. For more information please contact: Peter W. Tsao, PhD, Vice President Corporate Development Tel: +886-2-8177-7072 firstname.lastname@example.org To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/taigen-biotechnology-to-establish-a-new-company-with-hec-pharmaceutical-in-china-for-treatment-of-chronic-hepatitis-c-300353821.html
PubMed | Lanzhou University, TaiGen Biotechnology Co Ltd and CAS Shanghai Institute of Materia Medica
Type: Journal Article | Journal: Acta pharmacologica Sinica | Year: 2014
To evaluate the effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans.Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al(3+) and 496 mg of Mg(2+)) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe(2+)) or calcium carbonate (containing 600 mg of Ca(2+)).Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0-) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0- for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0- by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0- by 17.8%, Cmax by 14.3%, and Ae by 18.4%.Metal ions, Al(3+), Mg(2+), and Fe(2+) markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca(2+) had much weaker effects. To avoid the effects of Al(3+) and Mg(2+)-containing drugs, nemonoxacin should be administered 2 h before them.
PubMed | The General Hospital of Shenyang Military Region, TaiGen Biotechnology Co., Lanzhou University and CAS Shanghai Institute of Materia Medica
Type: | Journal: Drug design, development and therapy | Year: 2016
To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans.Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine nemonoxacin concentrations were determined using validated liquid chromatography-tandem mass spectrometry methods.Coadministration of nemonoxacin with probenecid reduced the renal clearance (CLr) of nemonoxacin by 22.6%, and increased the area under the plasma concentration-time curve from time 0 to infinity (AUC0-) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CLr of nemonoxacin by 13.3% and increased AUC0- by 9.4%. Coadministration of nemonoxacin with probenecid or cimetidine did not significantly affect the maximum concentration of nemonoxacin or the percentage of the administered dose recovered in the urine.Although probenecid reduced the CLr and increased the plasma exposure of nemonoxacin, these effects are unlikely to be clinically meaningful at therapeutic doses. Cimetidine had weaker, clinically meaningless effects on the pharmacokinetics of nemonoxacin.
Lauderdale T.-L.,National Health Research Institute |
Shiau Y.-R.,National Health Research Institute |
Lai J.-F.,National Health Research Institute |
Chen H.-C.,TaiGen Biotechnology Co. |
King C.-H.R.,TaiGen Biotechnology Co.
Antimicrobial Agents and Chemotherapy | Year: 2010
The in vitro antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better in vitro activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci, Neisseria gonorrhoeae, and Haemophilus influenzae. The in vitro activity of TG-875649 was also comparable to or better than that of moxifloxacin against these pathogens, which included ciprofloxacinresistant, methicillin-resistant Staphylococcus aureus and levofloxacin-resistant Streptococcus pneumoniae. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
TaiGen Biotechnology Co. | Date: 2011-01-19
This invention relates to compounds of Formula (I), (II), or (III) shown in the specification. These compounds can be used to treat hepatitis C virus infection.
TaiGen Biotechnology Co. | Date: 2014-09-30
A method of mobilizing cells expressing the type 4 CXC chemokine receptor into the peripheral circulation by contacting them with an effective amount of a compound of formula (I) shown below (each variable in the formula being defined in the Specification): The method can be used to treat cancer and myocardial infarction.
PubMed | Fudan University and TaiGen Biotechnology Co.
Type: Journal Article | Journal: Antimicrobial agents and chemotherapy | Year: 2015
This study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy Chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. The study was composed of two stages. In the open-label stage, 500 mg or 750 mg of nemonoxacin (n = 12 each) was administered at an infusion rate of 5.56 mg/min. In the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n = 16 in each cohort; 12 subjects received the drug and the other 4 subjects received the placebo) was given at an infusion rate of 4.17 mg/min. The results showed that, in the first stage, the maximal nemonoxacin concentrations (mean SD) at steady state (Cmax_ss) were 9.60 1.84 and 11.04 2.18 g/ml in the 500-mg and 750-mg cohorts, respectively; the areas under the concentration-time curve at steady state (AUC0-24_ss) were 44.03 8.62 and 65.82 10.78 g h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 1.47, 8.17 1.76, and 9.96 2.23 g/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0-24_ss values were 40.46 9.52, 54.17 12.10, and 71.34 17.79 g h/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively. No accumulation was found after the 10-day infusion with any regimen. The drug was well tolerated. A Monte Carlo simulation indicated that the cumulative fraction of response of any dosing regimen was nearly 100% against Streptococcus pneumoniae. The probability of target attainment of nemonoxacin therapy was >98% when the MIC of nemonoxacin against S. pneumoniae was 1 mg/liter. It is suggested that all of the studied intravenous nemonoxacin dosing regimens should have favorable clinical and microbiological efficacies in future clinical studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.).
News Article | October 30, 2016
TAIPEI, Taiwan, Oct. 30, 2016 /PRNewswire/ -- TaiGen Biotechnology Co., Ltd. ("TaiGen") announced today that its wholly owned subsidiary, TaiGen Biopharmaceuticals Co. (Beijing), Ltd. has signed an agreement with YiChang HEC ChangJiang Pharmaceutical Co., Ltd ("HEC") to establish a new...