RA-9 | CAS#919091-63-7 | DUBS Inhibitor

MedKoo Cat#: 408099 | Name: RA-9

Description:

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

RA-9 is a potent and selective proteasome-associated deubiquitinating enzymes (DUBs) inhibitor with favorable toxicity profile and anticancer activity.

Chemical Structure

RA-9

CAS#919091-63-7

Theoretical Analysis

MedKoo Cat#: 408099

Name: RA-9

CAS#: 919091-63-7

Chemical Formula: C19H15N3O5

Exact Mass: 365.1012

Molecular Weight: 365.35

Elemental Analysis: C, 62.46; H, 4.14; N, 11.50; O, 21.90

Price and Availability

Size	Price	Availability
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 5,950.00	2 Weeks

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Related CAS #

No Data

Synonym

RA-9; RA 9; RA9; RA-9 UPS inhibitor

IUPAC/Chemical Name

(3E,5E)-3,5-Bis[(4-nitrophenyl)methylene]-4-piperidinone

InChi Key

YUYPWAMLWZVHAE-KAVGSWPWSA-N

InChi Code

InChI=1S/C19H15N3O5/c23-19-15(9-13-1-5-17(6-2-13)21(24)25)11-20-12-16(19)10-14-3-7-18(8-4-14)22(26)27/h1-10,20H,11-12H2/b15-9+,16-10+

SMILES Code

O=C1/C(CNC/C1=C\C2=CC=C([N+]([O-])=O)C=C2)=C/C3=CC=C([N+]([O-])=O)C=C3

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

>3 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

Ovarian cancer is the deadliest of the gynecologic malignancies. Carcinogenic progression is accompanied by upregulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUB) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer.

Product Data

Product Data

Instruction

View handling instruction

Biological target:

RA-9 blocks ubiquitin-dependent protein degradation without impacting 20S proteasome proteolytic activity. RA-9 selectively induces onset of apoptosis in ovarian cancer cell lines and primary cultures derived from donors. RA-9 induces endoplasmic reticulum (ER)-stress responses in ovarian cancer cells.

In vitro activity:

RA‑9 exerted an inhibitory effect on the adhesion and proliferation of H2373 cells, whereas it had no effect on A549 cells. In H2373 cells, treatment with RA‑9 decreased its phosphorylation compared to the DMSO control. Reference: Int J Oncol. 2020 Jul;57(1):80-86. https://pubmed.ncbi.nlm.nih.gov/32236606/

In vivo activity:

This study demonstrated that RA-9 is efficient in exerting cytotoxic effects and inhibitory actions on cell proliferation and hormone secretion by modulating the expression of pERK1/2, pCREB and p27. Inhibition of USP8 might be a strategy to target both USP8-WT and USP8-mutated tumors in CD patients. Reference: Endocr Relat Cancer. 2021 Jun 28;28(8):573-582. https://pubmed.ncbi.nlm.nih.gov/34086599/

	Solvent	mg/mL	mM
Solubility
	DMSO	4.2	11.41

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 365.35 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. Mirzapoiazova T, Pozhitkov A, Nam A, Mambetsariev I, Nelson MS, Tan YC, Zhang K, Raz D, Singhal S, Nasser MW, Kulkarni P, Batra SK, Sattler M, Salgia R. Effects of selected deubiquitinating enzyme inhibitors on the proliferation and motility of lung cancer and mesothelioma cell lines. Int J Oncol. 2020 Jul;57(1):80-86. doi: 10.3892/ijo.2020.5034. Epub 2020 Apr 1. PMID: 32236606; PMCID: PMC7252467. 2. Vogel RI, Coughlin K, Scotti A, Iizuka Y, Anchoori R, Roden RB, Marastoni M, Bazzaro M. Simultaneous inhibition of deubiquitinating enzymes (DUBs) and autophagy synergistically kills breast cancer cells. Oncotarget. 2015 Feb 28;6(6):4159-70. doi: 10.18632/oncotarget.2904. PMID: 25784654; PMCID: PMC4414179. 3. Winkel AF, Engel CK, Margerie D, Kannt A, Szillat H, Glombik H, Kallus C, Ruf S, Güssregen S, Riedel J, Herling AW, von Knethen A, Weigert A, Brüne B, Schmoll D. Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling. J Biol Chem. 2015 Nov 20;290(47):28446-28455. doi: 10.1074/jbc.M115.678136. Epub 2015 Oct 12. PMID: 26459563; PMCID: PMC4653701. 4. Coughlin K, Anchoori R, Iizuka Y, Meints J, MacNeill L, Vogel RI, Orlowski RZ, Lee MK, Roden RB, Bazzaro M. Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin Cancer Res. 2014 Jun 15;20(12):3174-86. doi: 10.1158/1078-0432.CCR-13-2658. Epub 2014 Apr 11. PMID: 24727327; PMCID: PMC4269153.

In vitro protocol:

In vivo protocol:

1. Winkel AF, Engel CK, Margerie D, Kannt A, Szillat H, Glombik H, Kallus C, Ruf S, Güssregen S, Riedel J, Herling AW, von Knethen A, Weigert A, Brüne B, Schmoll D. Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling. J Biol Chem. 2015 Nov 20;290(47):28446-28455. doi: 10.1074/jbc.M115.678136. Epub 2015 Oct 12. PMID: 26459563; PMCID: PMC4653701. 2. Coughlin K, Anchoori R, Iizuka Y, Meints J, MacNeill L, Vogel RI, Orlowski RZ, Lee MK, Roden RB, Bazzaro M. Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin Cancer Res. 2014 Jun 15;20(12):3174-86. doi: 10.1158/1078-0432.CCR-13-2658. Epub 2014 Apr 11. PMID: 24727327; PMCID: PMC4269153.

1: Treppiedi D, Di Muro G, Marra G, Barbieri AM, Mangili F, Catalano R, Serban A, Ferrante E, Locatelli M, Lania AG, Arosio M, Spada A, Peverelli E, Mantovani G. USP8 inhibitor RA-9 reduces ACTH release and cell growth in tumor corticotrophs. Endocr Relat Cancer. 2021 Jun 28;28(8):573-582. doi: 10.1530/ERC-21-0093. PMID: 34086599. 2: Coughlin K, Anchoori R, Iizuka Y, Meints J, MacNeill L, Vogel RI, Orlowski RZ, Lee MK, Roden RB, Bazzaro M. Small-molecule RA-9 inhibits proteasome- associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin Cancer Res. 2014 Jun 15;20(12):3174-86. doi: 10.1158/1078-0432.CCR-13-2658. Epub 2014 Apr 11. PMID: 24727327; PMCID: PMC4269153.