SirReal2 is a novel, highly potent and isoform-selective inhibitor of Sirt2 (Sirtuin 2) with potential anticancer and anti-inflammatory activity. It inhibits Sirt2 (Sirtuin 2) with an IC50 of 140 nM. The Sirtuins are a highly conserved class of NAD+-dependent lysine deacylases. The human isotype Sirtuin 2 (Sirt2) deacetylates both cytoplasmatic and nuclear proteins and it has been implicated in the pathogenesis of cancer, neurodegeneration, and inflammation. Therefore, the modulation of Sirt2 activity is a promising strategy for pharmaceutical intervention.

Physicochemical Properties

Molecular Formula	C22H20N4OS2
Molecular Weight	420.55
Exact Mass	420.107
CAS #	709002-46-0
Related CAS #	709002-46-0
PubChem CID	1096292
Appearance	Off-white to light yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.701
LogP	5.83
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	29
Complexity	541
Defined Atom Stereocenter Count	0
InChi Key	MENNDDDTIIZDDN-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H20N4OS2/c1-14-10-15(2)25-22(24-14)28-13-20(27)26-21-23-12-18(29-21)11-17-8-5-7-16-6-3-4-9-19(16)17/h3-10,12H,11,13H2,1-2H3,(H,23,26,27)
Chemical Name	2-[(4,6-Dimethyl-2-pyrimidinyl)thio]-N-[5-(1-naphthalenylmethyl)-2-thiazolyl]acetamide
Synonyms	SirReal 2; SirReal-2; SirReal2
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro activity: SirReal2 selectively inhibits Sirt2 via a Sirt2-specific amino acid network, and induces a tubulin hyperacetylation and a significant depletion of BubR1 in HeLa cells. Kinase Assay: SirReal2 is a potent, isotype-selective Sirt2 inhibitor with an IC50 value of 140 nM and has very little effect on the activities of Sirt3-5. SirReal2 leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1
ln Vivo	In vivo, SirReal2 inhibits Sirt2 activity without affecting the activity of the other Class-I sirtuins Sirt1 and Sirt3.
Animal Protocol	SirReal2 (12.5, 25, and 50 μM) treatment did not induce the increase in acetylation of p53 N/A
References	[1]. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun. 2015 Feb 12;6:6263. [2]. Structure-Based Development of an Affinity Probe for Sirtuin 2. Angew Chem Int Ed Engl. 2016;55(6):2252-2256.

Solubility Data

Solubility (In Vitro)

DMSO: 84 mg/mL (199.7 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3778 mL	11.8892 mL	23.7784 mL
	5 mM	0.4756 mL	2.3778 mL	4.7557 mL
	10 mM	0.2378 mL	1.1889 mL	2.3778 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.