scholarly journals In vivo and in vitro characterization of the B1 and B2 zinc-binding domains from the acute promyelocytic leukemia protooncoprotein PML.

1996 ◽  
Vol 93 (4) ◽  
pp. 1601-1606 ◽  
Author(s):  
K. L. Borden ◽  
J. M. Lally ◽  
S. R. Martin ◽  
N. J. O'Reilly ◽  
E. Solomon ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Zinc Binding ◽  
Binding Domains ◽  
In Vitro Characterization

Asymmetric synthesis and in vivo/in vitro characterization of new hybrid anticonvulsants derived from (2,5-dioxopyrrolidin-1-yl)phenylacetamides

2021 ◽  
Vol 109 ◽  
pp. 104751
Author(s):  
Michał Abram ◽  
Anna Rapacz ◽  
Gniewomir Latacz ◽  
Bartłomiej Szulczyk ◽  
Justyna Kalinowska-Tłuścik ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
In Vitro Characterization

In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2862-2864 ◽  
Author(s):  
Bruno Cassinat ◽  
Sylvie Chevret ◽  
Fabien Zassadowski ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Event Free Survival ◽  
Free Survival ◽  
Acid Sensitivity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.

scholarly journals In vivo and in vitro characterization of overproduced colicin E9 immunity protein

1992 ◽  
Vol 207 (2) ◽  
pp. 687-695 ◽  
Author(s):  
Russell WALLIS ◽  
Ann REILLY ◽  
Arthur ROWE ◽  
Geoffrey R. MOORE ◽  
Richard JAMES ◽  
...  
Keyword(s):  
Immunity Protein ◽  
In Vitro Characterization ◽  
Colicin E9

scholarly journals Identification of a Novel Delta Opioid Receptor Agonist Chemotype with Potential Negative Allosteric Modulator Capabilities

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7236
Author(s):  
Yazan J. Meqbil ◽  
Hongyu Su ◽  
Robert J. Cassell ◽  
Kendall L. Mores ◽  
Anna M. Gutridge ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Clinical Drug Development ◽  
In Vitro Characterization ◽  
Opioid Receptor Agonist ◽  
Negative Allosteric Modulator ◽  
Δ Opioid Receptor ◽  
Clinical Drug

The δ-opioid receptor (δOR) holds great potential as a therapeutic target. Yet, clinical drug development, which has focused on δOR agonists that mimic the potent and selective tool compound SNC80 have largely failed. It has increasingly become apparent that the SNC80 scaffold carries with it potent and efficacious β-arrestin recruitment. Here, we screened a relatively small (5120 molecules) physical drug library to identify δOR agonists that underrecruit β-arrestin, as it has been suggested that compounds that efficaciously recruit β-arrestin are proconvulsant. The screen identified a hit compound and further characterization using cellular binding and signaling assays revealed that this molecule (R995045, compound 1) exhibited ten-fold selectivity over µ- and κ-opioid receptors. Compound 1 represents a novel chemotype at the δOR. A subsequent characterization of fourteen analogs of compound 1, however did not identify a more potent δOR agonist. Computational modeling and in vitro characterization of compound 1 in the presence of the endogenous agonist leu-enkephalin suggest compound 1 may also bind allosterically and negatively modulate the potency of Leu-enkephalin to inhibit cAMP, acting as a ‘NAM-agonist’ in this assay. The potential physiological utility of such a class of compounds will need to be assessed in future in vivo assays.

scholarly journals Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo

Oncotarget ◽  
2016 ◽  
Vol 7 (29) ◽  
pp. 46028-46041 ◽  
Author(s):  
Farzaneh Atashrazm ◽  
Ray M. Lowenthal ◽  
Joanne L. Dickinson ◽  
Adele F. Holloway ◽  
Gregory M. Woods
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Therapeutic Potential ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

In vivo and in vitro characterization of rifampicine suppositories

2009 ◽  
Vol 19 (3) ◽  
pp. 217-221
Author(s):  
H.M. El-Nahas ◽  
F.S. Ghazy ◽  
H.A. El-Ghamry ◽  
A.M. El-Wsaby
Keyword(s):  
In Vitro Characterization

scholarly journals A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia

Blood ◽  
2020 ◽  
Author(s):  
Yun Tan ◽  
Xiaoling Wang ◽  
Huan Song ◽  
Yi Zhang ◽  
Rongsheng Zhang ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Target Genes ◽  
Synergistic Effects ◽  
Chromosome Translocation ◽  
Vital Role ◽  
Promyelocytic Leukemia ◽  
Super Enhancer ◽  
Transcriptional Deregulation

Transcriptional deregulation initiated by oncogenic fusion proteins plays a vital role in leukemia. The prevailing view is that the oncogenic fusion protein PML/RARα, generated by the chromosome translocation t(15;17), functions as a transcriptional repressor in acute promyelocytic leukemia (APL). Here we provide rich evidence of how PML/RARα drives oncogenesis through both repressive and activating functions, particularly the importance of the newly identified activation role for the leukemogenesis of APL. The activating function of PML/RARα is achieved by recruiting both abundant P300 and HDAC1 and by the formation of super-enhancers. All-trans retinoic acid and arsenic trioxide, two widely used drugs in APL therapy, exert synergistic effects on controlling super-enhancer-associated PML/RARα-regulated targets in APL cells. We utilize a series of in vitro and in vivo experiments to demonstrate that PML/RARα-activated target gene GFI1 is necessary for the maintenance of APL cells, and that PML/RARα, likely oligomerized, transactivates GFI1 through chromatin conformation at the super-enhancer region. Finally, we profile GFI1 targets and reveal the interplay between GFI1 and PML/RARα on chromatin in co-regulating target genes. Our study provides genomic insight into the dual role of fusion transcription factors in transcriptional deregulation to drive leukemia development, highlighting the importance of globally dissecting regulatory circuits.

In vivo and in vitro trimethadione oxidation activity of the liver from various animal species including mouse, hamster, rat, rabbit, dog, monkey and human

1999 ◽  
Vol 18 (1) ◽  
pp. 12-16 ◽  
Author(s):  
E Tanaka ◽  
A Ishikawa ◽  
T Horie
Keyword(s):  
Animal Species ◽  
In Vitro Study ◽  
Metabolic Clearance ◽  
Oxidation Activity ◽  
In Vitro Characterization ◽  
Demethylase Activity ◽  
Total Body

Trimethadione (TMO) has the properties required of a probe drug for the evaluation of hepatic drug-oxidizing capacity and, in this study, we have summarized the in vivo and in vitro metabolism of TMO in various animal species including mouse, hamster, rat, rabbit, dog, monkey and human. In the in vivo study, the plasma TMO level was measured after intravenous or oral (human) administration of TMO at a dose of 4 mg/kg to various animal species. The rate of TMO metabolic clearance in these animal species in vivo was in the order mouse > hamster >rat>rabbit>dog>monkey>human. In the in vitro study, species differences were observed in the cytochrome P450 (P450) content and drug-oxidizing enzyme activity. The content of P450 was monkey> mouse>dog>rabbit>hamster>rat>human. On the other hand, TMO N-demethylation was in the order mouse >hamster >rat >rabbit>dog>monkey>human. There was a good correlation between the mean total body clearance of TMO ( in vivo)andthemeanTMON-demethylase activity ( in vitro) (y=1.7×+0.11, r=0.965, P<0.001). These results show that TMO is a probe agent with metabolic and pharmacokinetic characteristics making it attractive for the in vivo and in vitro characterization of metabolic activity in various animal species.

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