| Stereochemistry | EPIMERIC |
| Molecular Formula | C9H16N2O6 |
| Molecular Weight | 248.2331 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 5 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N2CCC(O)NC2=O
InChI
InChIKey=UCKYOOZPSJFJIZ-XVKVHKPRSA-N
InChI=1S/C9H16N2O6/c12-3-4-6(14)7(15)8(17-4)11-2-1-5(13)10-9(11)16/h4-8,12-15H,1-3H2,(H,10,16)/t4-,5?,6-,7-,8-/m1/s1
Tetrahydrouridine is a potent competitive reversible inhibitor of cytidine deaminase. Tetrahydrouridine can inhibit cell proliferation by regulation of the cell cycle independent of cytidine deaminase (CDA) expression levels. Tetrahydrouridine may be useful for researching potential treatments for high CDA-expressing tumors. Tetrahydrouridine use, alone or in combination with the DNA methyltransferase inhibitor 5-fluoro-2’-deoxycytidine, is being evaluated in animal models and clinical trials for diseases, including cancer and mitochondrial DNA depletion syndrome.
CNS Activity
Originator
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
Tetrahydrouridine 10 mg/kg was administered 60 minutes before oral decitabine at 0.01, 0.02, 0.04, 0.08, or 0.16 mg/kg. Repeat dose administration 2X/week for 8 weeks
Route of Administration:
Oral
Panc-1, MIAPaCa-2, BxPC-3, H322, H441, and H1299 cells were seeded in 96-well plates at 2,500-5,000 cells/well in triplicate. After incubating for 12 hrs, cell viability was determined by treating cells with stepwise 4-fold serial dilutions of gemcitabine (from 100 mkM), and incubating at 37uC for 96 hrs with or without Tetrahydrouridine (THU). To evaluate cell viability, all cells were fixed with 25% glutaraldehyde for 30 min at room temperature and then stained with 200 mkl of 0.05% methylene blue for 20 min. The dye was eluted with 0.33 M HCl for 20 min with agitation. Absorbance was measured in a microplate reader (model 3550, Bio-Rad, Tokyo, Japan) at 598 nm.
ACTIVE MOIETY
