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530341 RPN13 Inhibitor, RA190 - CAS 1617495-03-0 - Calbiochem

RPN13 Inhibitor, RA190, is a cell-permeable compound that binds to cysteine 88 of ubiquitin receptor RPN13 Pru domain in the 19S regulatory particle and inhibits proteasome function.

FDS (Fiches de données de sécurité), certificats d’analyse (CoA) et de qualité (CoQ), dossiers, brochures et autres documents disponibles.

Synonymes: 3,5-bis(3,4-Dichlorobenzylidene)-1-(S-2-amino-3-phenyl)-piperidin-4-one, HCl, ADRM1 Inhibitor, Adhesion Regulating Molecule 1 Inhibitor, ARM1 Inhibitor; GP110 Inhibitor

Primary Target: RPN13/ADRM1
530341
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Aperçu

Replacement Information

Tableau de caractéristiques principal

CAS #Empirical Formula
1617495-03-0C₂₈H₂₂Cl₄N₂O₂ •HCl

Products

RéférenceConditionnement Qté
5303410001 Flacon en verre 10 mg
Description
OverviewA cell-permeable, bioavailable, non-toxic bis-benzylidine piperidone compound that directly and covalently binds to Cys88 of ubiquitin receptor RPN13 Pru domain (pleckstrin-like receptor for ubiquitin) in the 19S regulatory particle and inhibits proteasome function leading to rapid accumulation of polyubiquitinated proteins. Does not affect the chymotryptic, tryptic, and peptidyl-glutamyl peptide-hydrolyzing activities of the 20S core particle. Exhibits anti-proliferative effects against multiple myeloma cells (IC50 = 100 nM) and HPV transformed cells (IC50 = 300 nM). Acts synergistically with bortezomib (Cat. No. 504314) to diminish cervical cancer cell viability and is effective even in multiple myeloma cells that are resistant to bortezomib treatment. Elevates p53 and p53-regulated genes in HeLa, CaSki, and SiHa cervical cancer cells as observed with bortezomib. Shown to induce apoptosis via induction of endoplasmic reticulum stress and up-regulate ATF-4 protein and CHOP-10 and XBP1s mRNA levels prior to apoptosis in MM.1S and HeLa cells. Reduces the growth of multiple myeloma and ovarian cancer xenografts in mice without affecting spontaneous HPV-specific CD8+ T cell responses. Displays desirable pharmacokinetic properties with Cmax in about 2 hours and t1/2α = 4.2 h; t1/2β = 25.5 h following a 10 mg/kg dose (i.p).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
Catalogue Number530341
Brand Family Calbiochem®
Synonyms3,5-bis(3,4-Dichlorobenzylidene)-1-(S-2-amino-3-phenyl)-piperidin-4-one, HCl, ADRM1 Inhibitor, Adhesion Regulating Molecule 1 Inhibitor, ARM1 Inhibitor; GP110 Inhibitor
References
ReferencesAnchoori, R.K., et al. 2013. Cancer Cell. 24, 791.
Product Information
CAS number1617495-03-0
FormYellow solid
Hill FormulaC₂₈H₂₂Cl₄N₂O₂ •HCl
Chemical formulaC₂₈H₂₂Cl₄N₂O₂ •HCl
Hygroscopic Hygroscopic
ReversibleN
Quality LevelMQ100
Applications
Biological Information
Primary TargetRPN13/ADRM1
Purity≥97% by HPLC
Physicochemical Information
Cell permeableY
Dimensions
Materials Information
Toxicological Information
Safety Information according to GHS
Safety Information
Product Usage Statements
Storage and Shipping Information
Ship Code Ambient Temperature Only
Toxicity Standard Handling
Storage -20°C
Protect from Light Protect from light
Hygroscopic Hygroscopic
Do not freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Packaging Information
Packaged under inert gas Packaged under inert gas
Transport Information
Supplemental Information
Specifications
Global Trade Item Number
Référence GTIN
5303410001 04055977287295

Documentation

RPN13 Inhibitor, RA190 - CAS 1617495-03-0 - Calbiochem FDS

Titre

Fiche de données de sécurité des matériaux (FDS) 

Références bibliographiques

Aperçu de la référence bibliographique
Anchoori, R.K., et al. 2013. Cancer Cell. 24, 791.
Fiche technique

Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

Revision20-November-2015 JSW
Synonyms3,5-bis(3,4-Dichlorobenzylidene)-1-(S-2-amino-3-phenyl)-piperidin-4-one, HCl, ADRM1 Inhibitor, Adhesion Regulating Molecule 1 Inhibitor, ARM1 Inhibitor; GP110 Inhibitor
DescriptionA cell-permeable bis-benzylidine piperidone that covalently modifies RPN13/ADRM1 via Michael addition between its electrophilic enone and the nucleophilic RPN13 Cys88, most likely freeing pleckstrin-like receptor for ubiquitin (Pru) domain from intramolecular interaction with the UCH37-binding domain and thereby allowing non-proteasome-associated RPN13 to compete against proteasome 19S regulatory particle- (RP-) incorporated RPN13 for ubiquitinated substrates binding, without affecting RPN13 RP assembly, 20S core particle (CP) proteolytic activities, or the deubiquitinase activity of UCH37 or RP. RPN13 blockage not only prevents many pro-apoptotic factors from degradation, the buildup of cellular ubiquitinated proteins in general also effectively triggers ER unfold protein response (UPR), accounting for the observed RA190 anticancer activity, notably in Multiple Myeloma (IC50 in nM = 35/MM.1S, 50/NCI-H929, 75/ANBL6,100/RPMI-8226), HPV+ cervical cancer (IC50 in nM = 150/HeLa, 300/CasKi, 750/HiHa), and HPV16-transformed oral keratinocyte HOK-16B (IC50 = 600 nM) cultures. RA190 is bioavailable via either oral or intraperitoneal administration in mice with tissue distribution in blood and major organs except brain and effectively inhibits NCI-H929 (20 mg/kg/d, i.p.), ES-2 (10 mg/kg/d, i.p.), and TC-1 (40 mg/kg/72 h, p.o.) tumor growths, as well as prevents 4UbFL reporter degradation in skin via topical application in mice in vivo without signs of adverse effects to animals or compromised host immune response. Synergizes with the 20S CP proteolytic activity inhibitor Bortezomib (Cat. No. 504314) in HeLa killing and is active against Bortezomib-resistant RPMI-8226-V10R and ANBL6-V10R cultures.
FormYellow solid
Intert gas (Yes/No) Packaged under inert gas
CAS number1617495-03-0
Chemical formulaC₂₈H₂₂Cl₄N₂O₂ •HCl
Purity≥97% by HPLC
SolubilityDMSO (50 mg/ml). Use only fresh DMSO for reconstitution. Only sparingly soluble in water (5 mg/ml).
Storage Protect from light
-20°C
Hygroscopic
Do Not Freeze Ok to freeze
Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity Standard Handling
ReferencesAnchoori, R.K., et al. 2013. Cancer Cell. 24, 791.