TAS-106

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H13N3O5
Molecular Weight	267.238
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)N(C=C1)[C@@H]2O[C@H](CO)[C@](O)(C#C)[C@H]2O

InChI

InChIKey=JFIWEPHGRUDAJN-DYUFWOLASA-N

InChI=1S/C11H13N3O5/c1-2-11(18)6(5-15)19-9(8(11)16)14-4-3-7(12)13-10(14)17/h1,3-4,6,8-9,15-16,18H,5H2,(H2,12,13,17)/t6-,8+,9-,11-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/3-c-ethynylcytidine | https://adisinsight.springer.com/drugs/800008251 | https://clinicaltrials.gov/ct2/show/NCT00737360

3'-C-ethynylcytidine (Ethynylcytidine, TAS-106) is a synthetic cytidine nucleoside containing a covalently bound ethynyl group with potential antineoplastic and radiosensitizing activities. 3'-C-ethynylcytidine is metabolized in tumor cells to ethynylcytidine triphosphate (ECTP), which inhibits RNA synthesis by competitive inhibition of RNA polymerases I, II and III; subsequently, RNase L is activated, resulting in apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves singled stranded RNA, causes 28s rRNA fragmentation, and activates Janus Kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule. Development of a cytosine derivative of 3'-ethynyl ribonucleoside, TAS-106, as an intravenously administered treatment for solid tumours was discontinued. A phase II trial in patients with head and neck cancer was terminated in the US.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA-directed RNA polymerase I subunit RPA1 3 Target ID: O95602 Gene ID: 25885.0 Gene Symbol: POLR1A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23609829 \| https://www.ncbi.nlm.nih.gov/pubmed/20839029	Blocker 555
DNA-directed RNA polymerase II subunit RPB1 2 Target ID: P24928 Gene ID: 5430.0 Gene Symbol: POLR2A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23609829 \| https://www.ncbi.nlm.nih.gov/pubmed/20839029	Blocker 555
DNA-directed RNA polymerase III subunit RPC1 1 Target ID: O14802 Gene ID: 11128.0 Gene Symbol: POLR3A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/23609829 \| https://www.ncbi.nlm.nih.gov/pubmed/20839029	Blocker 555

PubMed

Title	Date	PubMed
Synthesis and in vitro activities of new anticancer duplex drugs linking 2'-deoxy-5-fluorouridine (5-FdU) with 3'-C-ethynylcytidine (ECyd) via a phosphodiester bonding.	2009-10-01	19744858
PK-PD modeling of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine and the enhanced antitumor effect of its phospholipid derivatives in long-circulating liposomes.	2009-07-30	19426792
1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo.	2009-05	19360349
Role of RNase L in apoptosis induced by 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine.	2009-04	18668243
Inhibition of HIF-1alpha by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo.	2008-11-04	18854835
Cytotoxic nucleoside analogues: different strategies to improve their clinical efficacy.	2008	18473803
Cellular localization and functional characterization of the equilibrative nucleoside transporters of antitumor nucleosides.	2007-10	17711502
Mechanism of action of a new antitumor ribonucleoside, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), differs from that of 5-fluorouracil.	2007-06	17487404
Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106, effectively suppresses the growth of tumor cells transplanted in mice.	2007-05-01	17448876
An apoptotic pathway of 3'-Ethynylcytidine(ECyd) involving the inhibition of RNA synthesis mediated by RNase L.	2006	17150838
X irradiation induces the proapoptotic state independent of the loss of clonogenic ability in Chinese hamster V79 cells.	2005-07	15966763
Possible antitumor activity of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106) against an established gemcitabine (dFdCyd)-resistant human pancreatic cancer cell line.	2005-05	15904471
Synthesis and biological evaluation of branched and conformationally restricted analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd).	2005-04-01	15755661
Synthesis and biological evaluation of nucleobase-modified analogs of the anticancer compounds 3'-C-ethynyluridine (EUrd) and 3'-C-ethynylcytidine (ECyd).	2005-02-15	15670934
Synthesis and biological evaluation of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd).	2005	16247958
A novel anticancer ribonucleoside, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine, enhances radiation-induced cell death in tumor cells.	2004-12	15548113
Synthesis of the cyclic and acyclic acetal derivatives of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine, a potent antitumor nucleoside. Design of prodrugs to be selectively activated in tumor tissues via the bio-reduction-hydrolysis mechanism.	2003-05-29	12735992
Determination of 3'-C-ethynylcytidine in human plasma and urine by liquid chromatographic-electrospray ionization tandem mass spectrometry.	2003-02-05	12560048
Sensitivity of human cancer cells to the new anticancer ribo-nucleoside TAS-106 is correlated with expression of uridine-cytidine kinase 2.	2002-07	12149149
Cellular and biochemical mechanisms of the resistance of human cancer cells to a new anticancer ribo-nucleoside, TAS-106.	2002-04	11985795
Anticancer mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine (ECyd, TAS-106).	2002	12903195
1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106)1: antitumor effect and mechanism of action.	2001-09-21	11563078
Cloning and expression of uridine/cytidine kinase cDNA from human fibrosarcoma cells.	2001-09	11494055
Improvement in precision of the liquid chromatographic-electrospray ionization tandem mass spectrometric analysis of 3'-C-ethynylcytidine in rat plasma.	2001-04-15	11318405
Antitumor activity and pharmacokinetics of TAS-106, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine.	2001-03	11267946
Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd).	2001	12836350

Sample Use Guides

In Vivo Use Guide

Thirty patients were treated with 66 courses of TAS-106 at eight dose levels ranging from 0.67-9.46 mg/m(2). A cumulative sensory peripheral neuropathy was the principal dose-limiting toxicity (DLT) of TAS-106 at the 6.31 mg/m(2) dose level, which was determined to be the maximum tolerated dose (MTD). The recommended phase II dose of TAS-106 is 4.21 mg/m(2).

Route of Administration: Intravenous

In Vitro Use Guide

he IC50 values of Ethynylcytidine in the five human tumors with 4, 24 and 72 h exposure range from 0.114 to 1.032 uM, 0.015 to 0.067 uM, and 0.008 to 0.058 uM, respectively.

Name

Type

Language

TAS-106

Common Name

English

1-(3-C-ETHYNYL-.BETA.-D-RIBO-PENTOFURANOSYL)CYTOSINE

Preferred Name

English

3'-C-ETHYNYLCYTIDINE

Systematic Name

English

2(1H)-PYRIMIDINONE, 4-AMINO-1-(3-C-ETHYNYL-.BETA.-D-RIBOFURANOSYL)-

Common Name

English

TAS 106 [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1557