KW-2478 819812-04-9

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight:

574.66 KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1.


Biological Activity


KW-2478 inhibits the binding of bRD to Hsp90α with IC50 of 3.8 nM.
KW-2478 degradates the Hsp90 client Proteins, including FGFR3 and
IGF-1Rβand c-Raf-1. KW-2478 reduces the level of phosphorylated Erk1/2.
KW-2478 induces Apoptosis by cleavage of PARP, a substrate of caspase-3
In U266 cells,. KW-2478 has Time dependency of antiproliferative
activity, consecutive drug exposure for at least 12 hours is necessary
to to exert potent antitumor activity. KW-2478 downregulates the
translocation products of IgH locus.


KW-2478 inhibits the transcription
of c-Maf and cyclin D1 genes by mainly suppressing the function of
Cdk9. KW-2478 has potent and broad growth inhibitory activities against
various cell lines, KW-2478 inhibites cancer cell growth in all cell
lines, with EC50 of 101-252 nM, 81.4-91.4 nM and 120-622 nM for B-cell
lymphoma, mantle cell lymphoma and multiple myeloma, respectively.
KW-2478 also shows potent growth inhibitory activity in primary CLL and
NHL cells with EC50 of 40-170 nM and 200-400 nM, respectively.


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.


Protocol(Only for Reference)


Kinase Assay: [1]

Hsp90 Binding Assay

Human Hsp90α solution (0.5 μg/mL) is fixed on 96-well plates, followed by blocking with TBS containing 1% bovine serum albumin. KW-2478 solutions is added to the wells, and bRD is added to a concentration of 0.1 μmol/L. After removal of solution, poly-HRP streptavidin solution dilutes with poly-HRP dilution buffer is added to the wells. After removal of solution, equal volumes of TMB peroxidase substrate and peroxidase solution B are added to the wells. To stop the HRP reaction, 2 mol/L H2SO4 are added, followed by measurement of absorbance at 450 nm using a microplate spectrophotometer.

Cell Assay: [1]

Cell lines	Human Hsp90α solution (0.5 μg/mL) is fixed on 96-well plates, followed by blocking with TBS containing 1% bovine serum albumin. KW-2478 solutions is added to the wells, and bRD is added to a concentration of 0.1 μmol/L. After removal of solution, poly-HRP
Concentrations	0.05 - 5 μM
Incubation Time	3 days
Method	To measure the IC50, OPM-2/green fluorescent protein (GFP) cells, KMS-11 cells, OPM-2/GFP and other cells are plated into 96-well plates and treat with KW-2478. After 72 hours of cultivation, cell viability is determined using Cell Proliferation Reagent WST-1. WST reagent is 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 is measured with a microplate spectrophotometer. To examine time dependency of antiproliferative activity of KW-2478, the cells are plated into 96-well V-bottomed plates and treated with KW-2478. After 0 hour and at intervals from 3 to 72 hours at 37 °C, the supernatant is aspirated. After drug-free medium is added to the wells, the supernatant is aspirated again. Finally, drug-free medium is added to the wells, and the plates are further incubated for the remainder of the 72-hour period, followed by measurement of cell viabil

Animal Study: [1]

Animal Models	NCI-H929 tumors s.c. inoculated in SCID mice, OPM-2/GFP i.v. inoculated mouse model
Formulation	sterile 0.9% sodium chloride solution
Dosages	25, 50 , 100 and 200 mg/kg
Administration	Orally administrated once daily for 5 days
Solubility	30% propylene glycol, 5% Tween 80, 65% D5W, 10 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Chemical Information

Molecular Weight (MW)	574.66
Formula	C30H42N2O9
CAS No.	819812-04-9

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	115 mg/mL (200.11 mM)
		Water	<1 mg/mL (
		Ethanol	3 mg/mL (5.22 mM)
	In vivo	30% propylene glycol, 5% Tween 80, 65% D5W	10 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	2-(2-ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxyethyl)acetamide

Molarity Calculator
Dilution Calculator
Molecular Weight Calculator

Contact us if you need more details on 819812-04-9. We are ready to answer your questions on packaging, logistics, certification or any Other aspects about 819812-04-9 KW-2478、KW-2478. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Cytoskeletal Signaling > HSP Inhibitor