| Stereochemistry | ABSOLUTE |
| Molecular Formula | C29H40N2O9 |
| Molecular Weight | 560.6359 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 6 / 6 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CO[C@H]1C[C@H](C)CC2=C(OC)C(=O)C=C(NC(=O)\C(C)=C\C=C[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)C2=O
InChI
InChIKey=QTQAWLPCGQOSGP-KSRBKZBZSA-N
InChI=1S/C29H40N2O9/c1-15-11-19-25(34)20(14-21(32)27(19)39-7)31-28(35)16(2)9-8-10-22(37-5)26(40-29(30)36)18(4)13-17(3)24(33)23(12-15)38-6/h8-10,13-15,17,22-24,26,33H,11-12H2,1-7H3,(H2,30,36)(H,31,35)/b10-8-,16-9+,18-13+/t15-,17+,22+,23+,24-,26+/m1/s1
Geldanamycin, an antimicrobial compound, was purified in 1970 from the culture filtrates of Streptomyces hygroscopicus var. geldanus var. nova. Geldanamycin is moderately active in vitro against protozoa, bacteria, and fungi. It also has an antineoplastic effect against some cancer cells growing in culture. Molecular studies revealed the binding of geldanamycin to members of the heat shock protein 90 (HSP90) family of molecular chaperones. Interference with the function of these HSPs seems to be the major mechanism of action of geldanamycin.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 0.714 µM [Kd] | |||
| 0.152 µM [Kd] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
PubMed
Patents
Sample Use Guides
Maximum tolerated doses were approximately 20 mg/kg for the mice and 4 mg/kg for the dog.
Route of Administration:
Intravenous
The mechanism of action of geldanamycin was investigated with murine lymphoblastoma L5178Y cells. The agent inhibited the cell growth at concentrations over 0.01 micrograms/ml. Geldanamycin blocked DNA polymerase alpha more markedly than beta and gamma. The degree of inhibition depended upon concentrations of the enzyme but not upon those of template, suggesting a drug-enzyme interaction. IC50 for DNA polymerase alpha was 10 micrograms/ml and for DNA polymerase beta 100 micrograms/ml at low concentrations of enzyme. The inhibition of DNA polymerase alpha by the antibiotic was non-competitive and Ki was 20 microM.
METABOLITE (PARENT)
METABOLITE (PARENT)
SUBSTANCE RECORD
