| Stereochemistry | ABSOLUTE |
| Molecular Formula | C19H28ClNO6 |
| Molecular Weight | 401.882 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]1([C@H](OC)[C@@H](CC[C@]12CO2)OC(=O)NC(=O)CCl)[C@@]3(C)O[C@@H]3CC=C(C)C
InChI
InChIKey=MSHZHSPISPJWHW-PVDLLORBSA-N
InChI=1S/C19H28ClNO6/c1-11(2)5-6-13-18(3,27-13)16-15(24-4)12(7-8-19(16)10-25-19)26-17(23)21-14(22)9-20/h5,12-13,15-16H,6-10H2,1-4H3,(H,21,22,23)/t12-,13-,15-,16-,18+,19+/m1/s1
| Molecular Formula | C19H28ClNO6 |
| Molecular Weight | 401.882 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
TNP-470 (AGM-1470, (3R,4S,5S,6R)-5-methoxy-4- [(2R,3R)-2-methyl-3-(3-methyl-2-butenyl) -oxiranyl]-1-oxaspiro[2,5]oct-6-yl(chloroacetyl) carbamate) is an anti-angiogenic, semisynthetic analogue of fumagillin, a known antibiotic secreted by the fungus Aspergillus fumigatus fresenius, which is under clinical development for the treatment of cancer by Takeda Chemical Industries Ltd. in Japan and TAP Pharmaceuticals, Inc. in the United States. TNP-470 binds to and irreversibly inactivates methionine aminopeptidase-2 (MetAP2), resulting in endothelial cell cycle arrest late in the G1 phase and inhibition of tumor angiogenesis. This agent may also induce the p53 pathway, thereby stimulating the production of cyclin-dependent kinase inhibitor p21 and inhibiting angiogenesis. In early clinical reports, TNP-470 is tolerated up to 177 mg/m(2) with neurotoxic effects (fatigue, vertigo, ataxia, and loss of concentration) being the principal dose-limiting toxicity (DLT). TNP-470 is being evaluated in Phase I-II trials in the US in patients with Kaposi’s sarcoma, cervical cancer, breast cancer, brain cancer, prostate cancer and renal cell carcinoma.
CNS Activity
Approval Year
Doses
AEs
Sourcing
PubMed
Patents
Sample Use Guides
60 mg/m(2) infused over 1h three times per week
Route of Administration:
Intravenous
KB cells were seeded on a 10-cm plastic dish (Falcon,; Becton Dickinson Labware, Lincoln Park, NJ) at 1 x 10^6 cells/well in complete medium. After 24-, 48- and 72 hour-treatments with anti-IL-8 antibody and/or TNP470 (0, 1, 10, 100, 100 ng/ml), KB cell proliferation was determined by cell counting after washing with cold phosphate-buffered saline (PBS), trypsinizing and staining with trypan saline. In the in vitro study, the combination treatment of TNP470 and anti-IL-8 antibody significantly reduced the proliferation of KB cells.