| Stereochemistry | ABSOLUTE |
| Molecular Formula | C16H20N4O5 |
| Molecular Weight | 348.3538 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CO[C@]12[C@@H]3[C@H](CN1C4=C([C@H]2COC(N)=O)C(=O)C(N)=C(C)C4=O)N3C
InChI
InChIKey=HRHKSTOGXBBQCB-VFWICMBZSA-N
InChI=1S/C16H20N4O5/c1-6-10(17)13(22)9-7(5-25-15(18)23)16(24-3)14-8(19(14)2)4-20(16)11(9)12(6)21/h7-8,14H,4-5,17H2,1-3H3,(H2,18,23)/t7-,8+,14+,16-,19?/m1/s1
Porfiromycin is an N-methyl derivative of the antineoplastic antibiotic mitomycin-C initially isolated from Streptomyces ardus. Upon administration, the drug undergoes chemical or enzymatic reduction, followed by spontaneous loss of the tertiary methoxy (hydroxyl) group and formation of an aromatic indole system. Thus activated, porfiromycin generates oxygen radicals and alkylates DNA, producing interstrand cross-links and single-strand breaks at guanosine residues. Porfiromycin was tested in phase III for head and neck carcinoma, however, its development was terminated.
Approval Year
Sourcing
PubMed
Patents
Sample Use Guides
In clinical trials, patients received 75 mg/m2 porfiromycin every 6-8 weeks as a single bolus i.v. injection. In conjunction with radiation treatment, 40 mg/m2 porfiromycin was given on Days 5 and 47 (or last day) of Radiation treatment.
Route of Administration:
Intravenous
The cytotoxicity, metabolism, and DNA alkylation of porfiromycin (PFM) under aerobic and hypoxic conditions were evaluated in P388 murine leukemia cells. Clonogenic assays showed that the IC50 value for a 1-h exposure to PFM was 4 microM for aerobic cells and 0.5 microM for hypoxic cells. After a 1-h exposure to concentrations of 1, 5, and 10 microM [14C]-PFM, the accumulation of total radioactivity in hypoxic cells was 10 to 20 times that in aerobic cells.
ACTIVE MOIETY
