SW-100 (SW100), a tetrahydroquinoline-based compound, is a novel, potent, brain penetrant and selective histone deacetylase 6 (HDAC6) inhibitor (IC50 = 2.3 nM) with neuroprotective effects.HDAC6 exhibits selectivity that is at least 1000 times greater than that of all other HDAC isozymes. The ability of SW-100 to cross the blood-brain barrier is noticeably better. Since there are currently no effective treatments or cures for fragile X syndrome (FXS), disease-modifying therapies are required. SW-100 can enhance memory function in an FXS mouse model using Fmr1-/-mice. This tiny molecule exhibits at least a thousand-fold selectivity over all other class I, II, and IV HDAC isoforms, good brain penetration, and low-nanomolar potency for the inhibition of HDAC6 (IC50 = 2.3 nM). Furthermore, SW-100 selectively restores the reduced levels of acetylated α-tubulin in the hippocampus of Fmr1-/- mice by inhibiting the α-tubulin deacetylase domain of HDAC6 (CD2), which in turn increases α-tubulin acetylation in cells without affecting histone acetylation. Finally, by improving a number of memory and learning deficits in Fmr1-/-mice, SW-100 models the intellectual deficiencies linked to FXS, which is compelling evidence to support the development of HDAC6-based treatments for this uncommon illness.

Physicochemical Properties

Molecular Formula	C17H17CLN2O2
Molecular Weight	316.782083272934
Exact Mass	316.1
Elemental Analysis	C, 64.46; H, 5.41; Cl, 11.19; N, 8.84; O, 10.10
CAS #	2126744-35-0
Related CAS #	2126744-35-0
PubChem CID	130345472
Appearance	Light yellow to yellow solid powder
LogP	3.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	385
Defined Atom Stereocenter Count	0
InChi Key	MNAYBFFSFQRSIT-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H17ClN2O2/c18-15-7-8-16-14(10-15)2-1-9-20(16)11-12-3-5-13(6-4-12)17(21)19-22/h3-8,10,22H,1-2,9,11H2,(H,19,21)
Chemical Name	4-[(6-chloro-3,4-dihydro-2H-quinolin-1-yl)methyl]-N-hydroxybenzamide
Synonyms	SW-100; SW 100; SW100
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

Targets	HDAC1 (IC50 = 5.23 μM); HDAC2 (IC50 = 32.8 μM); HDAC3 (IC50 = 29.5 μM); HDAC4 (IC50 = 10.9 μM); HDAC5 (IC50 = 4.07 μM); HDAC6 (IC50 = 2.3 nM); HDAC7 (IC50 = 4.55 μM); HDAC8 (IC50 = 3.72 μM); HDAC9 (IC50 = 3.46 μM); HDAC10 (IC50 = 26.2 μM); HDAC11 (IC50 = 5.72 μM)
ln Vitro	SW-100 (0.01-10 µM; 48 hours) exhibits a clear, dose-dependent increase in the levels of acetylated α-tubulin[1].
ln Vivo	SW-100 (20 mg/kg; i.p.; twice a day for two days) improves a number of memory and learning deficits, such as novel object recognition, temporal ordering, and coordinate and categorical spatial processing of Fragile X syndrome[1].
Cell Assay	Cell Line: HEK293 cells Concentration: 0.01, 0.1, 1, 10 µM Incubation Time: 48 hours Result: Showed obvious increase in the acetylated α-tubulin levels in a dose-dependent manner.
Animal Protocol	8-10 weeks old C57BL/6 mice (Fmr1-/- mice)[1] 20 mg/kg Intraperitoneal injection; twice a day for two days
References	[1]. Brain Penetrable Histone Deacetylase 6 Inhibitor SW-100 Ameliorates Memory and LearningImpairments in a Mouse Model of Fragile X Syndrome. ACS Chem Neurosci. 2019 Mar 20;10(3):1679-1695.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 125 mg/mL (~394.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.57 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 (6.57 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 (6.57 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	3.1568 mL	15.7838 mL	31.5676 mL
	5 mM	0.6314 mL	3.1568 mL	6.3135 mL
	10 mM	0.3157 mL	1.5784 mL	3.1568 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.