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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H12N2O5S
Molecular Weight 260.267
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIAZOFURIN

SMILES

NC(=O)C1=CSC(=N1)[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O

InChI

InChIKey=FVRDYQYEVDDKCR-DBRKOABJSA-N
InChI=1S/C9H12N2O5S/c10-8(15)3-2-17-9(11-3)7-6(14)5(13)4(1-12)16-7/h2,4-7,12-14H,1H2,(H2,10,15)/t4-,5-,6-,7-/m1/s1

HIDE SMILES / InChI

Description

Tiazofurin (NSC-286193; 2-beta-D-ribofuranosylthiazole-4-carboxamide) an approved chronic myeloid leukemia (CML) drug, is converted by cellular enzymes into tiazofurin adenine dinucleotide, TAD, which inhibits the enzyme as a cofactor mimic. Resistance to tiazofurin is quickly developed due to diminished ability of resistant cells to synthesize TAD and increased enzymatic degradation of TAD. It is a nucleoside analog with oncolytic activity being developed by Ribapharm (formerly ICN Pharmaceuticals) as a potential treatment for leukemia. Ribapharm, through a Russian subsidiary of ICN, is planned to conduct phase II studies of tiazofurine involving patients suffering from advanced ovarian cancer or multiple myeloma which is resistant to conventional therapy.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
Tiazofurin was given by IV infusion (2200-2700 mg/m2 per day) for up to 10 days. Leukemia blasts rapidly disappeared from the circulation of patients during treatment, while mature myeloid cells in the marrow increased in number. Although these hematologic responses were transient, persisting less than 3-4 weeks, our findings confirm that Tiazofurin has anti-leukemia activity.
Route of Administration: Intravenous
In Vitro Use Guide
Concentration of tiazofurin required to reduce the number of cells in a culture by 50% with respect to control cultures was 0.51 uM for Lewis lung carcinoma cell lines (LLAK), 2.6 uM for in vitro cell line (LLTC), and greater than 10 uM for a range of human cancer cell lines. In cytotoxicity assays involving a 2-hour drug exposure followed by clonogenic assay, tiazofurin was more toxic to LLAK cells than to LLTC cells or L1210 murine leukemia cells, consistent with its high in vivo activity against LL. MM-96 human melanoma cells were highly resistant.