SIS17 is a novel, potent and isoform-selective inhibitor of mammalian histone deacetylase 11 (HDAC 11) with an IC50 value of 0.83 μM. SIS17 is active in cells and prevented serine hydroxymethyl transferase 2, a known HDAC11 substrate, from being demyristoylated without interfering with the activity of other HDACs. Other classes of enzymes may benefit from the development of isoform-specific inhibitors through the application of activity-guided design. Enzymes belonging to the class known as mammalian histone deacetylases (HDACs) are crucial components of biological pathways. Current HDAC inhibitors have a limited degree of selectivity and target several HDACs. One-specific HDAC-targeting inhibitors will be helpful in learning more about the biological roles of HDACs and in creating more effective treatments. Although little is known about HDAC11's biological role or enzymatic activity, recent reports indicate that it has effective defatty-acylation activity and that blocking it may be helpful in treating a range of human conditions, such as metabolic disorders, multiple sclerosis, and viral infections.

Physicochemical Properties

Molecular Formula	C21H38N2OS
Molecular Weight	366.604224681854
Exact Mass	366.27
Elemental Analysis	C, 68.80; H, 10.45; N, 7.64; O, 4.36; S, 8.75
CAS #	2374313-54-7
PubChem CID	139035087
Appearance	White to off-white solid powder
LogP	8.7
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	17
Heavy Atom Count	25
Complexity	312
Defined Atom Stereocenter Count	0
InChi Key	HSHXDCVZWHOWCS-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H38N2OS/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18-22-23-21(24)20-17-16-19-25-20/h16-17,19,22H,2-15,18H2,1H3,(H,23,24)
Chemical Name	N'-hexadecylthiophene-2-carbohydrazide
Synonyms	SIS17; SIS-17; SIS 17
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 is not stable in solution, please use freshly prepared working solution for optimal results.
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

Targets	HDAC11 ( IC50 = 0.83 μM )
ln Vitro	In MCF7 cells, SIS17 (0-50 μM, 6 hours) raises the fatty acylation level of SHMT2 [1]. In K562 cells, SIS17 (48 hours) in combination with oxaliplatin demonstrated good cytotoxicity [2].
References	[1]. Activity-Guided Design of HDAC11-Specific Inhibitors. ACS Chem Biol. 2019 Jul 19;14(7):1393-1397. [2]. A pan-cancer analysis identifies HDAC11 as an immunological and prognostic biomarker. FASEB J. 2022 Jul;36(7):e22326.

Solubility Data

Solubility (In Vitro)

DMSO: 73~100 mg/mL (199.1~272.8 mM) Ethanol: 18 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.67 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 mg/mL (5.46 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 20.0 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	2.7278 mL	13.6388 mL	27.2777 mL
	5 mM	0.5456 mL	2.7278 mL	5.4555 mL
	10 mM	0.2728 mL	1.3639 mL	2.7278 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.