Cambinol (formerly NSC-112546) is a potent SIRT (silent information regulator enzymes) inhibitor with IC50 values of 56 and 59 μM for SIRT1 and SIRT2, respectively. It inhibits NAD-dependent deacetylase activity of human SIRT1 and SIRT2. Inhibition of SIRT1 activity with cambinol during genotoxic stress leads to hyperacetylation of key stress response proteins and promotes cell cycle arrest. Treatment of BCL6-expressing Burkitt lymphoma cells with cambinol as a single agent induced apoptosis, which was accompanied by hyperacetylation of BCL6 and p53. Because acetylation inactivates BCL6 and has the opposite effect on the function of p53 and other checkpoint pathways, the antitumor activity of cambinol in Burkitt lymphoma cells may be accomplished through a combined effect of BCL6 inactivation and checkpoint activation. Cambinol was well tolerated in mice and inhibited growth of Burkitt lymphoma xenografts.

Physicochemical Properties

Molecular Formula	C21H16N2O2S
Molecular Weight	360.43
Exact Mass	360.093
CAS #	14513-15-6
Related CAS #	14513-15-6
PubChem CID	3246390
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	667ºC at 760mmHg
Melting Point	235 °C(dec.)
Flash Point	357.2ºC
Vapour Pressure	2.12E-18mmHg at 25°C
Index of Refraction	1.771
LogP	4.71
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	26
Complexity	597
Defined Atom Stereocenter Count	0
InChi Key	RVNSQVIUFZVNAU-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H16N2O2S/c24-18-11-10-13-6-4-5-9-15(13)16(18)12-17-19(14-7-2-1-3-8-14)22-21(26)23-20(17)25/h1-11,24H,12H2,(H2,22,23,25,26)
Chemical Name	5-((2-hydroxynaphthalen-1-yl)methyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
Synonyms	SIRT 1/2 inhibitor IV; SIRT1 Inhibitor II; SIRT2 Inhibitor VI; NSC112546; NSC-112546; NSC 112546
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
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	Human SIRT1 and SIRT2 NAD-dependent deacetylase activity is inhibited by cambinol. Using Cambinol to inhibit SIRT1 activity during genotoxic stress causes important stress response proteins to become hyperacetylated, which in turn encourages cell cycle arrest. When cambinol is used alone to treat BCL6-expressing Burkitt lymphoma cells, it causes apoptosis along with hyperacetylation of p53 and BCL6. Cambinol exhibits no action against SIRT3 and only modest inhibition of SIRT5 (42% inhibition at 300 μM) [1].
ln Vivo	In mice, camebinol (100 mg/kg) is well tolerated and suppresses the growth of xenografts with Burkitt lymphoma. Animals treated with cambinol do not significantly lose weight in comparison to controls. Novel anticancer drugs could be NAD-dependent deacetylase inhibitors[1].
Animal Protocol	100 mg/kg cambinol was the highest dose that could be administered as a single i.v. injection Daudi Burkitt lymphoma cells (20 × 106) resuspended in PBS were administered s.c. into the flank of 6- to 8-week-old nonobese diabetic/severe combined immunodeficient male mice.
References	[1]. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006 Apr 15;66(8):4368-77. [2]. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020 Dec;35(1):1322-1330.
Additional Infomation	Cambinol is a beta-naphtol derivative that inhibits NAD-dependant deacetylases to reduce cell survival under stress. This activity is currently being investigated for its use as a cancer treatment. Mechanism of Action Cambinol inhibits the NAD-dependant deacetylases SIRT1 and SIRT2, members of a protein family known as sirtuins. Inhibiting SIRT1 and SIRT2 while cells are under stress increases acetylation of p53, Ku70, and Foxo3a. This inhibition sensitizes cells to the action of drugs like [etoposide] and [paclitaxel], not just other drugs that damage DNA. Although the mechanism of this sensitizing is not defined, it is not dependent on p53, Ku70, or Foxo3a. The independent mechanism suggests the existence of more molecular targets. Cambinol is noncompetitive against NAD and competitive against H-4 peptide, substrates of SIRT2. Inhibiting SIRT2 increases the acetylation of tubulin. Cambinol also increases the acetylation of BCL6, a protein necessary for oncogenesis. Cambinol is also a weak inhibitor of SIRT5.

Solubility Data

Solubility (In Vitro)

DMSO: >150 mg/mL Water: Ethanol:

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.77 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 (5.77 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	2.7745 mL	13.8723 mL	27.7446 mL
	5 mM	0.5549 mL	2.7745 mL	5.5489 mL
	10 mM	0.2774 mL	1.3872 mL	2.7745 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.