NMS-E973 | CAS# 1253584-84-7 | Hsp90 inhibitor

MedKoo Cat#: 551034 | Name: NMS-E973

Featured

Description:

WARNING: This product is for research use only, not for human or veterinary use.

NMS-E973 is a novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). NMS-E973 displays significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known Hsp90 client proteins, and with a favorable pharmacokinetic and safety profile. The efficacy profile of NMS-E973 suggests a potential for development in different clinical settings, including tumors that have become resistant to molecular targeted agents, particularly in cases of tumors which reside beyond the blood-brain barrier (BBB).

Chemical Structure

NMS-E973

CAS#1253584-84-7

Theoretical Analysis

MedKoo Cat#: 551034

Name: NMS-E973

CAS#: 1253584-84-7

Chemical Formula: C22H22N4O7

Exact Mass: 454.1488

Molecular Weight: 454.44

Elemental Analysis: C, 58.15; H, 4.88; N, 12.33; O, 24.64

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 3,650.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

No Data

Synonym

NMS-E973; NMSE973; NMS E973.

IUPAC/Chemical Name

5-[2,4-Dihydroxy-6-(4-nitrophenoxy)phenyl]-N-(1-methyl-4-piperidinyl)-3-isoxazolecarboxamide

InChi Key

YLQODGGPIHWTHR-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H22N4O7/c1-25-8-6-13(7-9-25)23-22(29)17-12-20(33-24-17)21-18(28)10-15(27)11-19(21)32-16-4-2-14(3-5-16)26(30)31/h2-5,10-13,27-28H,6-9H2,1H3,(H,23,29)

SMILES Code

O=C(C1=NOC(C2=C(OC3=CC=C([N+]([O-])=O)C=C3)C=C(O)C=C2O)=C1)NC4CCN(C)CC4

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

NMS-E973 is a potent and selective inhibitor of HSP90. NMS-E973 binds to the ATP binding site of Hsp90α with a DC50 of <10 nM.

In vitro activity:

This study found that NMS-E973 induces apoptosis and inhibits cell growth in glioblastoma cells in cell culture and xenograft models. As a proapoptotic Bcl-2 member, PUMA was induced by NMS-E973 in a p53-dependent manner in glioblastoma in cell culture, thereby inducing apoptosis in glioblastoma cells. Reference: Onco Targets Ther. 2018 Mar 20;11:1583-1593. https://pubmed.ncbi.nlm.nih.gov/29593424/

In vivo activity:

NMS-E973 induces tumor shrinkage in different human tumor xenografts, and is highly active in models of resistance to kinase inhibitors. Moreover, consistent with its brain penetration, NMS-E973 is active also in an intracranially implanted melanoma mouse model. Reference: Clin Cancer Res. 2013 Jul 1;19(13):3520-32. https://pubmed.ncbi.nlm.nih.gov/23674492/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	66.02
	DMSO	40.0	88.02
	Ethanol	30.0	66.02

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 454.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Sun L, Yang S, Chi G, Jin X. Hsp90 inhibitor NMS-E973 exerts the anticancer effect against glioblastoma via induction of PUMA-mediated apoptosis. Onco Targets Ther. 2018 Mar 20;11:1583-1593. doi: 10.2147/OTT.S160813. PMID: 29593424; PMCID: PMC5865573. 2. Barbagallo I, Parenti R, Zappalà A, Vanella L, Tibullo D, Pepe F, Onni T, Li Volti G. Combined inhibition of Hsp90 and heme oxygenase-1 induces apoptosis and endoplasmic reticulum stress in melanoma. Acta Histochem. 2015 Oct;117(8):705-11. doi: 10.1016/j.acthis.2015.09.005. Epub 2015 Oct 19. PMID: 26493719. 3. Brasca MG, Mantegani S, Amboldi N, Bindi S, Caronni D, Casale E, Ceccarelli W, Colombo N, De Ponti A, Donati D, Ermoli A, Fachin G, Felder ER, Ferguson RD, Fiorelli C, Guanci M, Isacchi A, Pesenti E, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Fogliatto G. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018. Epub 2013 Sep 19. Erratum in: Bioorg Med Chem. 2014 Jan 1;22(1):662. PMID: 24100158. 4. Fogliatto G, Gianellini L, Brasca MG, Casale E, Ballinari D, Ciomei M, Degrassi A, De Ponti A, Germani M, Guanci M, Paolucci M, Polucci P, Russo M, Sola F, Valsasina B, Visco C, Zuccotto F, Donati D, Felder E, Pesenti E, Galvani A, Mantegani S, Isacchi A. NMS-E973, a novel synthetic inhibitor of Hsp90 with activity against multiple models of drug resistance to targeted agents, including intracranial metastases. Clin Cancer Res. 2013 Jul 1;19(13):3520-32. doi: 10.1158/1078-0432.CCR-12-3512. Epub 2013 May 14. PMID: 23674492.

In vitro protocol:

In vivo protocol:

1. Brasca MG, Mantegani S, Amboldi N, Bindi S, Caronni D, Casale E, Ceccarelli W, Colombo N, De Ponti A, Donati D, Ermoli A, Fachin G, Felder ER, Ferguson RD, Fiorelli C, Guanci M, Isacchi A, Pesenti E, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Fogliatto G. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018. Epub 2013 Sep 19. Erratum in: Bioorg Med Chem. 2014 Jan 1;22(1):662. PMID: 24100158. 2. Fogliatto G, Gianellini L, Brasca MG, Casale E, Ballinari D, Ciomei M, Degrassi A, De Ponti A, Germani M, Guanci M, Paolucci M, Polucci P, Russo M, Sola F, Valsasina B, Visco C, Zuccotto F, Donati D, Felder E, Pesenti E, Galvani A, Mantegani S, Isacchi A. NMS-E973, a novel synthetic inhibitor of Hsp90 with activity against multiple models of drug resistance to targeted agents, including intracranial metastases. Clin Cancer Res. 2013 Jul 1;19(13):3520-32. doi: 10.1158/1078-0432.CCR-12-3512. Epub 2013 May 14. PMID: 23674492.

1: Barbagallo I, Parenti R, Zappalà A, Vanella L, Tibullo D, Pepe F, Onni T, Li Volti G. Combined inhibition of Hsp90 and heme oxygenase-1 induces apoptosis and endoplasmic reticulum stress in melanoma. Acta Histochem. 2015 Oct;117(8):705-11. doi: 10.1016/j.acthis.2015.09.005. Epub 2015 Oct 19. PubMed PMID: 26493719. 2: Brasca MG, Mantegani S, Amboldi N, Bindi S, Caronni D, Casale E, Ceccarelli W, Colombo N, De Ponti A, Donati D, Ermoli A, Fachin G, Felder ER, Ferguson RD, Fiorelli C, Guanci M, Isacchi A, Pesenti E, Polucci P, Riceputi L, Sola F, Visco C, Zuccotto F, Fogliatto G. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90). Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018. Epub 2013 Sep 19. Erratum in: Bioorg Med Chem. 2014 Jan 1;22(1):662. PubMed PMID: 24100158. 3: Fogliatto G, Gianellini L, Brasca MG, Casale E, Ballinari D, Ciomei M, Degrassi A, De Ponti A, Germani M, Guanci M, Paolucci M, Polucci P, Russo M, Sola F, Valsasina B, Visco C, Zuccotto F, Donati D, Felder E, Pesenti E, Galvani A, Mantegani S, Isacchi A. NMS-E973, a novel synthetic inhibitor of Hsp90 with activity against multiple models of drug resistance to targeted agents, including intracranial metastases. Clin Cancer Res. 2013 Jul 1;19(13):3520-32. doi: 10.1158/1078-0432.CCR-12-3512. Epub 2013 May 14. PubMed PMID: 23674492.