Splitomicin (known also as Splitomycin), a lactone derived from naphthol, is a potent, cell-permeable and selective inhibitor of NAD(+)-dependent histone deacetylase (HDAC) Sir2p with potential antineoplastic activity. It inhibits Sir2p with an IC50 of 60 μM. Splitomicin was discovered for yeast sirtuins but showed rather weak inhibition on human enzymes.

Physicochemical Properties

Molecular Formula	C13H10O2
Molecular Weight	198.22
Exact Mass	198.068
CAS #	5690-03-9
Related CAS #	5690-03-9
PubChem CID	5269
Appearance	White to light yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	383.6±17.0 °C at 760 mmHg
Melting Point	73-74.5℃
Flash Point	161.2±18.4 °C
Vapour Pressure	0.0±0.9 mmHg at 25°C
Index of Refraction	1.656
LogP	3.03
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	0
Heavy Atom Count	15
Complexity	261
Defined Atom Stereocenter Count	0
InChi Key	ISFPDBUKMJDAJH-UHFFFAOYSA-N
InChi Code	InChI=1S/C13H10O2/c14-13-8-6-11-10-4-2-1-3-9(10)5-7-12(11)15-13/h1-5,7H,6,8H2
Chemical Name	1H-benzo[f]chromen-3(2H)-one
Synonyms	Splitomicin;Splitomycin
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	MCF-7 and H1299 cells are treated with splitomicin (10-333 μM) for 24 hours, and the antiproliferative impact is concentration-dependent. Splitomicin effectively suppresses MCF-7 and H1299 cell colony formation at 100 and 333 μM, but it is unable to decrease the number of colonies at 33 μM [2].
ln Vivo	Splitomicin increases tissue factor (TF) activity in the arterial vessel wall and speeds up carotid artery thrombosis in C57BL/6 mice when given intraperitoneally every 24 hours for five days at a dose of 80 mg/kg [3].
Cell Assay	Cell Proliferation Assay[2] Cell Types: Human breast cancer MCF-7 and lung cancer H1299 cells Tested Concentrations: 10, 33, 100, and 333 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited colony formation in a dose-dependent manner.
Animal Protocol	Animal/Disease Models: C57BL/6 mice aged 12-14 weeks weighing on average 27 g[3] Doses: 80 mg/kg Route of Administration: intraperitoneal (ip)injection every 24 h for 5 days Experimental Results: Increased TF activity in mouse carotid artery as compared with the controls .
References	[1]. Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15113-8. [2]. Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene. 2006 Jan 12;25(2):176-85. [3]. Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc Res. 2011 Feb 1;89(2):464-72.
Additional Infomation	Splitomicin is a benzochromenone that is 2,3-dihydro-1H-benzo[f]chromene substituted by an oxo group at position 3. It has been found to exhibit potential inhibitory activity against Sir2 proteins. It has a role as a Sir2 inhibitor and a platelet aggregation inhibitor. It is a benzochromenone, a delta-lactone and a naphtho-alpha-pyrone.

Solubility Data

Solubility (In Vitro)

DMSO:39 mg/mL (196.0 mM) Water:<1 mg/mL Ethanol:39 mg/mL (196.0 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (10.49 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 (10.49 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 (10.49 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	5.0449 mL	25.2245 mL	50.4490 mL
	5 mM	1.0090 mL	5.0449 mL	10.0898 mL
	10 mM	0.5045 mL	2.5224 mL	5.0449 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.