1105698-15-4

Basic information

• Product Name: N-[3-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]phenyl]-α-methylbenzeneacetamide
• Synonyms: N-[3-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]phenyl]-α-methylbenzeneacetamide;Salermide;N-{3-[(2-Hydroxy-naphthalen-1-ylmethylene)-amino]-phenyl}-2-phenyl-propionamide;SIRT1/2 Inhibitor VIII, Salermide
• CAS NO: 1105698-15-4
• Molecular Formula: C₂₆H₂₂N₂O₂
• Molecular Weight: 394.46508
• Mol File: 1105698-15-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 666.7±50.0 °C(Predicted)
• Appearance: /
• Density: 1.16±0.1 g/cm3(Predicted)
• Storage Temp.: Store at +4°C
• Solubility: DMSO: >10mg/mL
• PKA: 7.90±0.50(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO, DMF, or ethanol may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: N-[3-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]phenyl]-α-methylbenzeneacetamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[3-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]phenyl]-α-methylbenzeneacetamide(1105698-15-4)
• EPA Substance Registry System: N-[3-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]phenyl]-α-methylbenzeneacetamide(1105698-15-4)

Safety Data

• Hazard Codes: Xi
• Statements: 43-52/53
• Safety Statements: 36/37-61
• WGK Germany: 3
• Hazardous Substances Data: 1105698-15-4(Hazardous Substances Data)

Usage

Description

The sirtuins (SIRTs) are a family of NAD+-dependent histone deacetylases involved in gene regulation that is relevant to, e.g., longevity, cancer, gene regulation, energy homeostasis, and apoptosis. Salermide is an inhibitor of SIRT1 and SIRT2, causing tumor-specific apoptotic cell death. In MOLT4 leukemia cells, salermide causes 90% apoptosis within 72 hours (IC50 ~20 μM) by reactivating proapototic genes that are repressed by SIRT1.

Uses

Salermide is an inhibitor of SIRT1, SIRT2, and HDAC.

General Description

A cell-permeable 2-hydroxy-naphthaldehyde that acts as an inhibitor against sirtuins SirT1 and SirT2, members of class III HDACs. Salermide effectively inhibits the activity of both SirT1 and SirT2 (by 80% at 100 and 25 μM, respectively), while its structural analogue Sirtinol (Cat. Nos. 566320 and 566321), at 100 μM concentration, inhibits SirT2 only by up to 60% and is of no effect against SirT1. Salermide is also shown to be at least 2-fold more potent than Sirtinol (both at 100 μM) in killing leukemia KG1A and lymphoma Raji cultures.

Biochem/physiol Actions

Salermide is a novel Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2) inhibitor (III histone deacetylases inhibitor). In vitro Salermide has a stronger inhibitory effect on Sirt2 than on Sirt1. Salermide induces massive apoptosis in tumor cells. The activity was ascribed to effect of Salermide to the reactivation of proapoptotic genes epigenetically repressed exclusively in cancer cells by Sirt1. Salermide is a stronger Sirtuin inhibitor than sirtinol (Cat. No.S7942).

References

1) Lara?et al. (2009), Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect; Oncogene,?28?781 2) Pasco?et al. (2010),?Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues; J. Med. Chem.,?53?1407 3) Zhao?et al.?(2012),?Interactions between SIRT1 and MAPK/ERK regulate neuronal apoptosis induced by traumatic brain injury in vitro and in vivo; Exp. Neurol.,?237 489

Upstream product

• 492-37-5 hydratropic acid 
• 108-45-2 m-phenylenediamine 
• 1105698-16-5 (R/S)-N-(3-aminophenyl)-2-phenylpropanamide 
• 708-06-5 2-hydroxynaphthalene-1-carbaldehyde 

Relevant articles and documents

Discovery of salermide-related sirtuin inhibitors: Binding mode studies and antiproliferative effects in cancer cells including cancer stem cells

Chemical changes performed on 1a (sirtinol) led to a series of SIRT1/2 inhibitors, in some cases more potent than 1a mainly against SIRT1. Tested in human leukemia U937 cells, the benzamide and anilide derivatives 1b, 1c, 2b, and 2c as well as the 4-(2-phenylpropyl)thioanalogue 4c showed huge apoptosis induction, while some sulfinyl and sulfonyl derivatives (5b, 5c, and 6a-c) were highly efficient in granulocytic differentiation. When assayed in human leukemia MOLT4 as well as in human breast MDA-MB-231 and colon RKO cancer cell lines, the anilide 2b (salermide) and the phenylpropylthio analogue 4b emerged as the most potent antiproliferative agents. Tested on colorectal carcinoma and glioblastoma multiforme cancer stem cells (CSCs) from patients, 2b was particularly potent against colorectal carcinoma CSCs, while 4b, 6a, and the SIRT2-selective inhibitor AGK-2 showed the highest effect against glioblastoma multiforme CSCs. Such compounds will be further explored for their broad-spectrum anticancer properties.