NN-390 is a potent and specific HDAC6 inhibitor (antagonist) with IC50 of 9.8 nM. NN-390 penetrates the BBB (blood-brain barrier). NN-390 has research potential in metastatic group 3 medulloblastoma.

Physicochemical Properties

Molecular Formula	C17H16F4N2O4S
Molecular Weight	420.3785572052
Exact Mass	420.076
CAS #	2490284-25-6
PubChem CID	155699554
Appearance	Typically exists as solid at room temperature
LogP	2.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	6
Heavy Atom Count	28
Complexity	638
Defined Atom Stereocenter Count	0
InChi Key	SJWJGLIJTRUXIZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H16F4N2O4S/c1-9(2)23(8-10-3-5-11(6-4-10)17(24)22-25)28(26,27)13-7-12(18)14(19)16(21)15(13)20/h3-7,9,25H,8H2,1-2H3,(H,22,24)
Chemical Name	N-hydroxy-4-[[propan-2-yl-(2,3,4,5-tetrafluorophenyl)sulfonylamino]methyl]benzamide
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	NN-390 has little effect on non-cancer equivalents (IC50 in MRC-9 > 50 μM), but is cellularly potent with IC50 values of 1.19 μM in MV4-11 cells and 1.38 μM in MM.1S cells [1]. NN-390 (72 hours) considerably inhibits the self-renewal of BTIC-rich HD-MB03 cells and dramatically lowers the proliferation of HD-MB03 cells with an IC50 of 0.13 μM [1]. For one hour, NN-390 (0–2 μM) dramatically enhances α-tubulin acetylation while reducing acetylated histone H3. [1]. A dose-dependent increase in α-tubulin acetylation (0-0.2 μM) is observed with exposure to NN-390 (6 h) at concentrations as low as 0.1 μM [1]. NN-390 (0–2 μM, 24 hours) stimulates MV4-11 cells to undergo apoptosis [1].
ln Vivo	Plasma stability is improved by NN-390 (male CD-1 mice, i.p., single dose, 20 mg/kg) [1]. The PAMPA (Parallel Artificial Membrane Permeability Assay)-BBB (Blood-Brain Barrier) score can be raised with NN-390[1]. NN-390's pharmacokinetic characteristics in male CD-1 mice [1]. AUClast (h*ng/mL) 493 750 AUClast (KT-531 5a); NN-390 t1/2 (h) 1.05 1.90 Cmax (ng/mL) 1576 2523 AUClnf (h*ng/mL) 1519 2548 AUC/D (h *ng/mL) 79 126
Cell Assay	Immunofluorescence Cell Types: HeLa cells [1] Tested Concentrations: 0, 0.1, 0.25, 1, 2 μM Incubation Duration: 1 hour Experimental Results: Significant increase in α-tubulin acetylation and minimal change in acetylated histone H3. Western Blot Analysis Cell Types: AML (MV4-11) cells [1] Tested Concentrations: 0, 0.1, 0.5, 1, 5 μM Incubation Duration: 6 hrs (hours) Experimental Results: Concentrations as low as 0.1 μM and 0.1 μM resulted in α-tubulin Acetylation Limited acetylation of histone H3 occurs only at the highest concentration of 5 μM. Western Blot Analysis Cell Types: Group 3 MB (HD-MB03) cells [1] Tested Concentrations: 0, 0.053, 0.106, 0.158, 0.211 μM Incubation Duration: 6 hrs (hours) Experimental Results: α-Tubulin acetylation is dose-dependent starting from the lowest level The concentration-dependent increase was 53 nM, with no change observed in off-target histone H3 acetylation up to 211 nM. Apoptosis analysis Cell Types: MV4-11 cells [1] Tested Concentrations: 0, 0.25, 0.75, 1, 2 μM Incubation Duration: 24 hrs (hours) Experimental Results: Promote cancer cell apoptosis, 39% of cancer c
Animal Protocol	Animal/Disease Models: CD-1 mice (male, n=3) [1] Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection, single dose (pharmacokinetic/PK/PK analysis) Experimental Results: in Half-life in human plasma is 115 minutes, 2.8 - stability is increased exponentially.
References	[1]. Discovery of HDAC6-Selective Inhibitor NN-390 with in Vitro Efficacy in Group 3 Medulloblastoma. J Med Chem. 2022;65(4):3193-3217.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3788 mL	11.8940 mL	23.7880 mL
	5 mM	0.4758 mL	2.3788 mL	4.7576 mL
	10 mM	0.2379 mL	1.1894 mL	2.3788 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.