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)

+ [5]

Target

POLA1 x Ribonucleotide reductase

Mechanism

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

Therapeutic Areas

NeoplasmsDigestive System DisordersHemic and Lymphatic Diseases+ [1]

Active Indication-

Inactive Indication

Acute Myeloid LeukemiaAdenocarcinomaColonic Cancer+ [5]

Originator Organization

Sanofi

Active Organization-

Inactive Organization

Sanofi

Chiron Corp.Kyowa Hakko Kogyo Co., Ltd.

+ [1]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC10H14FN3O5

InChIKeyXPYQFIISZQCINN-QVXDJYSKSA-N

CAS Registry171176-43-5

Antineoplastic drugs are among the most toxic pharmaceuticals. Their release into the aquatic ecosystems has been reported, giving rise to concerns about the adverse effects, including cytotoxicity and genotoxicity, that they may have on exposed organisms. In this study, we analyzed the cytotoxicity and genotoxicity of 5-fluorouracil (5-FU) and its metabolite alpha-fluoro-beta-alanine (3-NH2-F); gemcitabine (GEM) and its metabolite 2'-deoxy-2',2'-difluorouridine (2-DOH-DiF); as well as cyclophosphamide (CP) on the HepG2 cell line. Drug concentrations were based on those previously observed in the effluent of a major cancer hospital in Brazil. The study found that GEM, 2-DOH-DiF and 5-FU resulted in reduced cell viability. No reduction in cell viability was observed for CP and 3-NH2-F. Genotoxic assessment revealed damage in the form of nucleoplasmic bridges for CP and 3-NH2-F. The tested concentrations of all compounds resulted in significantly increased MNi and NBUDs. The results showed that these compounds induced cytotoxic and genotoxic effects in HepG2 cells at concentrations found in the environment. To the best of our knowledge, this study is the first to report on the cytogenotoxic impacts of the metabolites 3-NH2-F and 2-DOH-DiF in HepG2 cells. These findings may help in the development of public policies that could minimize potential environmental contamination.

01 Sep 2022·ChemosphereQ2 · ENVIRONMENTAL SCIENCE & ECOLOGY

Functionalized metal-organic framework-derived carbon: Effective adsorbent to eliminate methylene blue, a small cationic dye from water

Q2 · ENVIRONMENTAL SCIENCE & ECOLOGY

Article

Author: Jhung, Sung Hwa ; Hossain, Md Abul ; Mondol, Md Mahmudul Hassan

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.

06 May 2021·Chemistry – A European Journal

Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes

Article

Author: Martín‐Pintado, Nerea ; Aviñó, Anna ; González, Carlos ; Mazzini, Stefania ; Cabrero, Cristina ; Gargallo, Raimundo ; Eritja, Ramon

AbstractWe report the structural effect of 2'‐deoxy‐2',2'‐difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self‐complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that are more pronounced in the case of the DNA : RNA hybrid. Analysis of the solution structures determined by NMR methods show that dFdC is an adaptable derivative that adopts North type sugar conformation when inserted in pure DNA, or a South sugar conformation in the context of DNA : RNA hybrids. In this latter context, South sugar pucker favors the formation of a 2'F⋅⋅H8 attractive interaction with a neighboring purine, which compensates the destabilizing effect of base pair distortions. These interactions share some features with pseudohydrogen bonds described previously in other nucleic acids structures with fluorine modified sugars.

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
Stomach Cancer	Phase 2	US	Chiron Corp.	01 Nov 2003
Metastatic Colorectal Carcinoma	Phase 2	US	Chiron Corp.	01 Jun 2003
Acute Myeloid Leukemia	Phase 2	US	-	-
Colonic Cancer	Phase 2	-	Matrix Pharmaceutical, Inc.	-
Colonic Cancer	Phase 2	-	Sanofi	-
Colonic Cancer	Phase 2	-	Kyowa Hakko Kogyo Co., Ltd.	-
Non-Small Cell Lung Cancer	Phase 2	US	-	-
Non-Small Cell Lung Cancer	Phase 2	-	Sanofi	-
Non-Small Cell Lung Cancer	Phase 2	-	Kyowa Hakko Kogyo Co., Ltd.	-
Non-Small Cell Lung Cancer	Phase 2	-	Matrix Pharmaceutical, Inc.	-