Quisinostat di-HCl (JNJ-26481585 di-HCl) is an orally bioactive and highly effective pan-HDAC inhibitor (antagonist) with IC50s of 0.11 nM, 0.33 nM, 0.64 nM, 0.46 nM and HDAC11 for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11 respectively. 0.37 nM. Quisinostat di-HCl has broad antineoplastic/anticancer activity.

Physicochemical Properties

Molecular Formula	C21H28CL2N6O2
Molecular Weight	467.39
Exact Mass	466.165
CAS #	875320-31-3
Related CAS #	Quisinostat;875320-29-9
PubChem CID	122129987
Appearance	White to yellow solid powder
Hydrogen Bond Donor Count	5
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	31
Complexity	533
Defined Atom Stereocenter Count	0
InChi Key	NRUIZESXVMJDKR-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H26N6O2.2ClH/c1-26-14-17(18-4-2-3-5-19(18)26)11-22-10-15-6-8-27(9-7-15)21-23-12-16(13-24-21)20(28)25-29;;/h2-5,12-15,22,29H,6-11H2,1H3,(H,25,28);2*1H
Chemical Name	N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide;dihydrochloride
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: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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 0.11 nM (IC50) HDAC2 0.33 nM (IC50) HDAC11 0.37 nM (IC50) HDAC10 0.46 nM (IC50) HDAC5 3.69 nM (IC50) HDAC8 4.26 nM (IC50) HDAC3 4.86 nM (IC50) HDAC9 32.1 nM (IC50) HDAC6 76.8 nM (IC50) HDAC7 119 nM (IC50)
ln Vitro	In vitro, JNJ-26481585 suppresses HDAC isozymes[1]. In tumor cells, JNJ-26481585 (30–1000 nM; 24 hours) is a strong pan-HDAC inhibitor[1]. JNJ-26481585 causes apoptosis and exhibits broad spectrum antiproliferative action against hematologic and solid cancer cell lines[1].
ln Vivo	p21waf1,cip1 ZsGreen tumors in vivo with JNJ-26481585 (40 mg/kg; po; once daily, for 3 days) as a strong HDAC1 inhibitor[1]. In vivo, JNJ-26481585 consistently causes H3 acetylation in tumor tissue[1]. Large pre-established HCT116 colon xenografts are vigorously inhibited in their growth by JNJ-26481585 (10 mg/kg; once daily; ip; for 14 days)[1].
Cell Assay	Western Blot Analysis[1] Cell Types: Human A2780 ovarian carcinoma cells Tested Concentrations: 30 nM, 100 nM, 300 nM, 1000 nM Incubation Duration: 24 hrs (hours) Experimental Results: Induced H3 and H4 acetylation at concentrations as low as 30 to 100 nM.
Animal Protocol	Animal/Disease Models: NMRI nude mice, with HCT116 colon carcinoma cells xenografts[1] Doses: 10 mg/kg Route of Administration: intraperitoneal (ip)injection, one time/day, for 14 days Experimental Results: Strongly inhibited the growth of large pre-established HCT116 colon xenografts.
References	[1]. JNJ-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. Clin Cancer Res. 2009 Nov 15;15(22):6841-51.

Solubility Data

Solubility (In Vitro)

DMSO : 31.25 mg/mL (66.86 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.45 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 (4.45 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 (4.45 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	2.1395 mL	10.6977 mL	21.3954 mL
	5 mM	0.4279 mL	2.1395 mL	4.2791 mL
	10 mM	0.2140 mL	1.0698 mL	2.1395 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.