| Stereochemistry | ABSOLUTE |
| Molecular Formula | C21H25N5O6 |
| Molecular Weight | 443.4531 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC2=C(C[C@@H](CCC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CN2)C(=O)N1
InChI
InChIKey=ZUQBAQVRAURMCL-DOMZBBRYSA-N
InChI=1S/C21H25N5O6/c22-21-25-17-14(19(30)26-21)9-12(10-23-17)2-1-11-3-5-13(6-4-11)18(29)24-15(20(31)32)7-8-16(27)28/h3-6,12,15H,1-2,7-10H2,(H,24,29)(H,27,28)(H,31,32)(H4,22,23,25,26,30)/t12-,15+/m1/s1
Lometrexol, formerly known as DDATHF; LY 264618; T-64 was the first glycinamide ribonucleotide formyl transferase (GARFT) inhibitor to be investigated clinically. Lometrexol had been in phase II clinical trial for the treatment non-small cell lung cancer (NSCLC). However, the studies have been discontinued by Tularik Inc, because Company had suggested, that drug would face competition from other companies in the indication
Approval Year
Doses
AEs
Sourcing
PubMed
Patents
Sample Use Guides
Patients receive oral folic acid once daily on days -7 to 6. Patients also receive lometrexol IV over 30-60 seconds on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed up to 2 months after removal from study and then every 3 months thereafter.
Route of Administration:
Intravenous
Inhibition of clonogenic potential by the glycinamideribonucleosyl transformylase inhibitor (DDATHF, Lometrexol) was evaluated in vitro in a human ovarian carcinoma cell line, SW626. Simultaneous treatment with 100 uM hypoxanthine completely prevented the inhibition of clonogenic potential caused by 0.5 uM DDATHF. DDATHF blocked cells in the early-middle S-phases of the cell cycle, and there was a corresponding marked reduction in the rate of DNA synthesis after drug withdrawal. DDATHF cytotoxicity differed moderately when folic acid concentrations varied between 0.22 and 0 uM, suggesting that folic acid does not necessarily antagonise DDATHF anti-tumour activity. Folinic acid at a concentration as low as 0.1 uM can completely rescue cells when given simultaneously with 0.5 uM DDATHF. When folinic acid was given 24 h after DDATHF, a reversal of cytotoxicity was observed at 0.5 and 1 uM, but to a much lesser extent than simultaneous treatment.
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
