Delving into the Latest Updates on Tezacitabine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2'-Deoxy-2'-(fluoromethylene)cytidine, FMdc, Tezacitabine (USAN)

+ [8]

Target

POLA1 x Ribonucleotide reductase

Action

inhibitors

Mechanism

POLA1 inhibitors(DNA polymerase alpha subunit inhibitors), RNR inhibitors(Ribonucleotide reductase inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Hematologic Neoplasms

Inactive Indication

Acute Myeloid LeukemiaAdenocarcinomaAdvanced Gastric Adenocarcinoma+ [5]

Originator Organization

Sanofi

Active Organization

Edison Oncology Holding Corp.

Inactive Organization

Kyowa Hakko Kogyo Co., Ltd.

Sanofi

Chiron Corp.

+ [1]

Drug Highest PhasePhase 1/2

First Approval Date-

RegulationOrphan Drug (United States)

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Structure/Sequence

Molecular FormulaC10H14FN3O5

InChIKeyXPYQFIISZQCINN-QVXDJYSKSA-N

CAS Registry171176-43-5

Elimination of organic dyes from wastewater is very important for our safe environment and sound health. In this work, adsorptive removal of cationic dyes, especially small ones, was investigated with carbonaceous materials to develop a competitive adsorption technology. To improve the performance of metal-organic framework (MOF)-derived carbons (MDCs) in dye adsorption, an MDC, derived from a MOF (MAF-6), was oxidatively functionalized with ammonium persulfate solutions (APSs). Although the porosity of pristine MDC decreased with functionalization via oxidation, functionalized MDCs (FMDCs), especially FMDC(1.0) that was obtained via treating MDC with APS (1.0 M), showed remarkable performances in the adsorption of small cationic dyes like methylene blue (MB) and azure B. For example, FMDC(1.0) had the maximum adsorption capacity (Q_o) of 625.0 mg/g (for MB) which is larger than any reported value with carbonaceous materials. Moreover, the obtained Q_o was around 4 and 2 times that of activated carbon with Q_o of 160 mg/g and MDC with Q_o of 298 mg/g, respectively. On the contrary, oxidative treatment of MDC was negative in adsorption of an anionic dye such as methyl orange. Moreover, the functionalized MDC was not very effective in the adsorption of cationic dyes with large sizes (like brilliant green, crystal violet, Janus green B, and rhodamine B) because of the limited pore size of the studied adsorbent FMDC(1.0). The remarkable adsorption of MB over FMDC(1.0) could be explained by electrostatic and π-π interactions. Finally, the facile recyclability of the FMDC(1.0) in MB adsorption was confirmed via successive adsorptions, FT-IR, and nitrogen adsorption; therefore, FMDC(1.0) can be suggested as a potential adsorbent to remove cationic dyes, especially with small molecular sizes.

01 Aug 2017·Journal of Cancer Research and Clinical Oncology

Clinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy?

Review

Author: Mannargudi, Mukundan Baskar ; Deb, Subrata

PURPOSERibonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation.METHODSThis review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016. A summary on whether their monotherapy or combination is still effective for further use is discussed.RESULTSAmong the RR2 inhibitors evaluated, GTI-2040, siRNA, gallium nitrate and didox were more efficacious as a monotherapy, whereas triapine was found to be more efficacious as combination agent. Hydroxyurea is currently used more in combination therapy, even though it is efficacious as a monotherapy. Gallium nitrate showed mixed results in combination therapy, while the combination activity of didox is yet to be evaluated. RR1 inhibitors that have long been used in chemotherapy such as gemcitabine, cladribine, fludarabine and clofarabine are currently used mostly as a combination therapy, but are equally efficacious as a monotherapy, except tezacitabine which did not progress beyond phase I trials.CONCLUSIONSBased on the results of clinical trials, we conclude that RR inhibitors are viable treatment options, either as a monotherapy or as a combination in cancer chemotherapy. With the recent advances made in cancer biology, further development of RR inhibitors with improved efficacy and reduced toxicity is possible for treatment of variety of cancers.

01 Jan 2007·Acta OncologicaQ2 · MEDICINE

Simultaneous alteration ofde novoandsalvagepathway to the deoxynucleoside triphosphate pool by (E)-2′-Deoxy-(fluoromethylene)cytidine (FMdC) and zidovudine (AZT) results in increased radiosensitivityin vitro

Q2 · MEDICINE

Article

Author: Coucke, Philippe A. ; Decosterd, Laurent A. ; Cottin, Eliane

To test whether a thymidine analog zidovudine (=AZT), is able to modify the radiosensitizing effects of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). A human colon cancer cell line Widr was exposed for 48 hours prior to irradiation to FMdC. Zidovudine was added at various concentrations immediately before irradiation. We measured cell survival and the effect of FMdC, AZT and FMdC + AZT on deoxynucleotide triphosphate pool. FMdC results in a significant increase of radiosensitivity. The enhancement ratios (ER =surviving fraction irradiated cells/surviving fraction drug treated and irradiated cells), obtained by FMdC or AZT alone are significantly increased by the combination of both compounds. Adding FMdC to AZT yields enhancement ratios ranging from 1.25 to 2.26. FMdC reduces dATP significantly, with a corresponding increase of TTP, dCTP and dGTP. This increase of TTP, dCTP and dGTP is abolished with the addition of AZT. Adding AZT to FMdC results in a significant increase of the radiosensitizing effect of FMdC. This combination appears to reduce the reactive enhancement of TTP, dCTP and dGTP induced by FMdC while it does not affect the inhibitory effect on dATP.

100 Deals associated with Tezacitabine

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External Link

KEGG	Wiki	ATC	Drug Bank
D06100	Tezacitabine	-	DB06433

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 2	-	Edison Oncology Holding Corp.	-
Metastatic Colorectal Carcinoma	Discovery	United States	Chiron Corp.	01 Jun 2003
Acute Myeloid Leukemia	Discovery	United States	-	-
Colonic Cancer	Discovery	-	Sanofi	-
Colonic Cancer	Discovery	-	Kyowa Hakko Kogyo Co., Ltd.	-
Colonic Cancer	Discovery	-	Matrix Pharmaceutical, Inc.	-
Non-Small Cell Lung Cancer	Discovery	-	Matrix Pharmaceutical, Inc.	-
Non-Small Cell Lung Cancer	Discovery	-	Sanofi	-
Non-Small Cell Lung Cancer	Discovery	United States	-	-
Non-Small Cell Lung Cancer	Discovery	-	Kyowa Hakko Kogyo Co., Ltd.	-