KW-2478

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H42N2O9.ClH
Molecular Weight	611.123
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCC1=C(O)C=C(O)C(C(=O)C2=CC(OC)=C(OCCN3CCOCC3)C=C2)=C1CC(=O)N(CCOC)CCOC

InChI

InChIKey=CKMGYWHSTADSIG-UHFFFAOYSA-N

InChI=1S/C30H42N2O9.ClH/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;1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20406843
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT01063907 | https://www.ncbi.nlm.nih.gov/pubmed/28873084 | https://clinicaltrials.gov/ct2/show/NCT00457782 | https://www.ncbi.nlm.nih.gov/pubmed/26695442

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

Targets

Primary Target	Pharmacology	Condition	Potency
Heat shock protein HSP90 35 Target ID: CHEMBL2095165 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20406843	Inhibitor 8297		3.8 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: https://clinicaltrials.gov/ct2/show/NCT00457782	Primary	Phase I 428	Unknown Approved Use Unknown
B-cell non-Hodgkin lymphoma 3 Sources: https://clinicaltrials.gov/ct2/show/NCT00457782	Primary	Phase I 428	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://clinicaltrials.gov/ct2/show/NCT01063907	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
6838 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	176 mg/m² single, intravenous dose: 176 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1990 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	47 mg/m² single, intravenous dose: 47 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2620 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	71 mg/m² single, intravenous dose: 71 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5410 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	132 mg/m² single, intravenous dose: 132 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
645 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	14 mg/m² 1 times / day single, intravenous dose: 14 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
11501 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	176 mg/m² single, intravenous dose: 176 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2758 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	47 mg/m² single, intravenous dose: 47 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3197 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	71 mg/m² single, intravenous dose: 71 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7876 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	132 mg/m² single, intravenous dose: 132 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
992 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	14 mg/m² 1 times / day single, intravenous dose: 14 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
5.43 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	176 mg/m² single, intravenous dose: 176 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	47 mg/m² single, intravenous dose: 47 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.29 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	71 mg/m² single, intravenous dose: 71 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.71 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	132 mg/m² single, intravenous dose: 132 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.05 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28873084	14 mg/m² 1 times / day single, intravenous dose: 14 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	KW-2478 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116328	https://www.001chemical.com/chem/search?q=DY116328
1PlusChem LLC	1P00G7E4	https://www.1pchem.com/search?query=1P00G7E4
AK Scientific	2503AH	https://aksci.com/item_detail.php?cat=2503AH
Angene	AGN-PC-0WH9JC	http://www.angenechemical.com/productshow/AGN-PC-0WH9JC.html
ApexBio Technology	A4062	https://www.apexbt.com/catalogsearch/result/?q=A4062
AstaTech	40628	http://astatechinc.com/CPSResult.php?CRNO=40628
BLD Pharm	BD379750	http://www.bldpharm.com/search/Search.html?keyword=BD379750
Chem Scene	CS-0007047	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0007047
ChemShuttle	104903	https://www.chemshuttle.com/catalogsearch/result/?q=104903
Debye Scientific	DA-33445	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-33445
Excenen	EX-A035	http://www.excenen.com/searchresultlist.php?id=EX-A035
Matrix Scientific	145251	http://www.matrixscientific.com/145251.html
MedChem Express	HY-13468	https://www.medchemexpress.com/search.html?q=HY-13468&ft=&fa=&fp=
MolPort	MolPort-021-804-965	https://www.molport.com/shop/molecule-link/MolPort-021-804-965
Molcore	MC116328	http://www.molcore.com/CatMC116328.html
Molnova	M16048	https://www.molnova.com/en/serch-list.html?keywords=M16048
Molnova	M17604	https://www.molnova.com/en/serch-list.html?keywords=M17604
MuseChem	I007541	https://www.musechem.com/product/I007541.html
Selleck Chemicals	S2685	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2685
ShangHai Biochempartner	BCP000481	http://www.biochempartner.com/search_BCP000481
ShangHai Biochempartner	BCP02906	http://www.biochempartner.com/search_BCP02906
TargetMol	T6558	https://www.targetmol.com/search?keyword=T6558
eMolecules	37153227	https://orderbb.emolecules.com/search/#?query=37153227
eNovation Chemicals	D372304	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372304&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-8613183035	https://mcule.com/MCULE-8613183035/

PubMed

Title	Date	PubMed
Phase I study of KW-2478, a novel Hsp90 inhibitor, in patients with B-cell malignancies.	2016 Jan 12	26695442

Patents

Sample Use Guides

In Vivo Use Guide

KW-2478 130 mg/m^2 Administered Days 1, 4, 8 and 11 of a 21 day cycle

Route of Administration: Intravenous

In Vitro Use Guide

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.

Name

Type

Language

KW-2478

Common Name

English

BENZENEACETAMIDE, 2-ETHYL-3,5-DIHYDROXY-N,N-BIS(2-METHOXYETHYL)-6-(3-METHOXY-4-(2-(4-MORPHOLINYL)ETHOXY)BENZOYL)-, MONOHYDROCHLORIDE

Common Name

English

KW 2478 [WHO-DD]

Common Name

English

Code System Code Type Description

FDA UNII

E628ZH6U2C