Phase I study of Gemtuzumab Ozogamicin given in combination with Enocitabine and Daunorubicin as induction therapy for elderly patients with acute myeloid leukemia - JALSG GML208-P1

Start Date01 Jan 2009

Sponsor / Collaborator-

100 Clinical Results associated with Enocitabine

100 Translational Medicine associated with Enocitabine

100 Patents (Medical) associated with Enocitabine

142

Literatures (Medical) associated with Enocitabine

01 Mar 2023·Metabolic Engineering

Implementation of the β-hydroxyaspartate cycle increases growth performance of Pseudomonas putida on the PET monomer ethylene glycol

Article

Author: Bar-Even, Arren ; Schada von Borzyskowski, Lennart ; Glatter, Timo ; Severi, Francesca ; Gómez-Coronado, Paul A ; Troncoso Castellanos, Mauricio ; Paczia, Nicole ; Erb, Tobias J ; Lindner, Steffen N ; Schulz-Mirbach, Helena

Ethylene glycol (EG) is a promising next generation feedstock for bioprocesses. It is a key component of the ubiquitous plastic polyethylene terephthalate (PET) and other polyester fibers and plastics, used in antifreeze formulations, and can also be generated by electrochemical conversion of syngas, which makes EG a key compound in a circular bioeconomy. The majority of biotechnologically relevant bacteria assimilate EG via the glycerate pathway, a wasteful metabolic route that releases CO₂ and requires reducing equivalents as well as ATP. In contrast, the recently characterized β-hydroxyaspartate cycle (BHAC) provides a more efficient, carbon-conserving route for C2 assimilation. Here we aimed at overcoming the natural limitations of EG metabolism in the industrially relevant strain Pseudomonas putida KT2440 by replacing the native glycerate pathway with the BHAC. We first prototyped the core reaction sequence of the BHAC in Escherichia coli before establishing the complete four-enzyme BHAC in Pseudomonas putida. Directed evolution on EG resulted in an improved strain that exhibits 35% faster growth and 20% increased biomass yield compared to a recently reported P. putida strain that was evolved to grow on EG via the glycerate pathway. Genome sequencing and proteomics highlight plastic adaptations of the genetic and metabolic networks in response to the introduction of the BHAC into P. putida and identify key mutations for its further integration during evolution. Taken together, our study shows that the BHAC can be utilized as 'plug-and-play' module for the metabolic engineering of two important microbial platform organisms, paving the way for multiple applications for a more efficient and carbon-conserving upcycling of EG in the future.

04 May 2021·Drug and Chemical ToxicologyQ4 · MEDICINE

Cardiotoxicity evaluation and comparison of diterpene alkaloids on zebrafish

Q4 · MEDICINE

Article

Author: Fang, Chengxin ; Liu, Hongmei ; Ye, Qiang ; Guo, Li ; Peng, Cheng ; Liu, Yushi ; Zhang, Tingmo ; Zhang, Cunyan ; Liu, Juanru ; Liu, Xiaomei

Diterpene alkaloids (DAs) have a broad spectrum of pharmacological activities, but exhibiting extremely serious cardiotoxicity to induce arrhythmia, heart arrest, even death. This study aimed to evaluate the cardiotoxicity of three diester diterpene alkaloids (DDAs) including aconitine (AC), mesaconitine (MAC), hypaconitine (HAC) and three monoester diterpene alkaloids (MDAs) including 14-α-benzoylaconine (BAC), 14-α-benzoylmesaconine (BMAC), 14-α-benzoylhypaconine (BHAC) on zebrafish. Firstly, the zebrafish embryos after a 72-hour post fertilization were treated with different doses of AC, MAC, HAC, and BAC, BMAC and BHAC for 2, 10 and 24 h, respectively. The heart rates of the treated embryos were calculated and the morphological images of body, together with heart fluorescence were obtained. Results demonstrated that AC, MAC, and HAC at low doses (15.6 and 31.3 μM) decreased the heart rates and increased them at high doses (62.5, 125, and 250 μM), while BAC, BMAC, and BHAC decreased the heart rates in the dose range of 31.3-250 μM, but the highest dose (500 μM) of BAC and BMAC increased the heart rates. In addition, AC, MAC, and HAC exhibited serious organic and functional toxicities, while BAC, BMAC, and BHAC did not. It could be induced that DDAs expressed stronger cardiotoxicities than MDAs, which might be due to that they were known as the Na⁺ channel activators and K⁺ channel inhibitors, respectively. The β-acetate at C-8 position, along with the protonated nitrogen on ring A of their chemical structures contributed more for their different cardiotoxicities. This is the first study on cardiotoxicity comparison of DAs, providing references for the rational and safe application of these compounds and some plant species containing them to reduce side effects while retaining therapeutic efficacy.

31 Dec 2020·BLOOD RESEARCH

Outcomes of pediatric acute myeloid leukemia patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era

Article

Author: Choi, Jung Yoon ; Shin, Hee Young ; Kim, Bo Kyung ; Kang, Hyoung Jin ; Hong, Kyung Taek ; Ahn, Hong Yul ; Choi, Sujin

BACKGROUNDAcute myeloid leukemia (AML) with internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with poor outcomes. This study aimed to analyze the outcomes of pediatric AML patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era.METHODSWe retrospectively reviewed and identified 18 patients diagnosed with non-M3 AML with FLT3-ITD mutations at Seoul National University Children's Hospital between May 2008 and August 2019.RESULTSThe median age was 13 years (range, 6?19 yr). The median follow-up time was 43 months (range, 6?157 mo). Fourteen patients received BH-AC-based (N4-Behenoy1-1-b-D-arabinofuranosy1cytosine) and 4 received cytarabine-based induction chemotherapy. Complete remission (CR) was achieved in 72.2% of the patients after the first induction chemotherapy and 80% of the patients achieved CR after salvage therapy. The overall CR rate was 94% (17/18 patients). These 17 patients underwent hematopoietic stem cell transplantation (9 matched unrelated donors, 5 matched related donors, and 3 haploidentical donors). Relapse occurred in 22% of the patients. Event free survival and overall survival rates were 53.8±12.1% and 53.6±12.1%, respectively, and they were not significantly different according to the type of induction chemotherapy (P=0.690) or the type of donor (P=0.102).CONCLUSIONThis study outlines the outcomes of pediatric AML patients with FLT3-ITD-mutations in one institution over a decade. Outcomes were significantly improved in this study compared to our previous report in 2004, where RFS and EFS were 0%. This study can provide baseline data for pediatric patients in the pre-FLT3 inhibitor era.

100 Deals associated with Enocitabine

External Link

KEGG	Wiki	ATC	Drug Bank
D01633	Enocitabine	L01BC	-

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Indication	Country/Location	Organization	Date
Leukemia	JP	Asahi Kasei Pharma Corp.	15 Dec 1982

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