| Stereochemistry | ACHIRAL |
| Molecular Formula | C30H42N2O9 |
| Molecular Weight | 574.6625 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC1=C(O)C=C(O)C(C(=O)C2=CC(OC)=C(OCCN3CCOCC3)C=C2)=C1CC(=O)N(CCOC)CCOC
InChI
InChIKey=VFUXSYAXEKYYMB-UHFFFAOYSA-N
InChI=1S/C30H42N2O9/c1-5-22-23(19-28(35)32(11-13-37-2)12-14-38-3)29(25(34)20-24(22)33)30(36)21-6-7-26(27(18-21)39-4)41-17-10-31-8-15-40-16-9-31/h6-7,18,20,33-34H,5,8-17,19H2,1-4H3
| Molecular Formula | C30H42N2O9 |
| Molecular Weight | 574.6625 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
KW-2478 is a novel and potent non-ansamycin inhibitor of heat shock protein 90 designed to overcome the limitations, including low water solubility and hepatotoxicity, of 17-allylamino-17-demethoxygeldanamycin (17-AAG). KW-2478 exerts a strong antitumor activity against multiple myeloma (MM) cells with various chromosomal translocations. KW-2478 inhibits cell growth and apoptosis associated with Hsp90 client protein degradation. Recent study results have revealed that KW-2478 is able to deplete Hsp90 client Cdk9 and the phosphorylated 4E-BP1, a transcriptional kinase and a transcription inhibitor respectively, leading to reduced expression of FGFR3, c-Maf, and cyclin D1. KW-2478 suppresses tumor growth and induces the degradation of client proteins in tumors in NCI-H929 s.c. inoculated model at doses of 100 mg/kg or more. KW-2478 reduces both serum M protein and MM tumor burden in the bone marrow in OPM-2/GFP i.v. inoculated mouse model at doses of 100 mg/kg.
Originator
Approval Year
Cmax
AUC
T1/2
Sourcing
PubMed
Patents
Sample Use Guides
KW-2478 130 mg/m^2 Administered Days 1, 4, 8 and 11 of a 21 day cycle
Route of Administration:
Intravenous
OPM-2/GFP and KMS-11 cells were used for activity evaluation. The cells were plated into 96-well plates and treated with KW-2478. After 72 hours of cultivation, cell viability was determined using Cell Proliferation Reagent WST-1 (Roche Diagnostics). WST reagent was added to the wells, followed by incubation for 4 hours at 37°C. After that, the absorbance at 450 nm with reference at 650 nm was measured with a microplate spectrophotometer.
