1. Cell Cycle/DNA Damage Epigenetics
  2. HDAC
  3. NN-390

NN-390 is a potent and selective HDAC6 inhibitor, with an IC50 of 9.8 nM. NN-390 penetrates the blood-brain barrier (BBB). NN-390 shows study potential in metastatic Group 3 MB (medulloblastoma).

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NN-390 Chemical Structure

NN-390 Chemical Structure

CAS No. : 2490284-25-6

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Description

NN-390 is a potent and selective HDAC6 inhibitor, with an IC50 of 9.8 nM. NN-390 penetrates the blood-brain barrier (BBB). NN-390 shows study potential in metastatic Group 3 MB (medulloblastoma)[1].

IC50 & TargetHDAC

HDAC6

9.8 nM (IC50)

HDAC3

>1 μM (IC50)

HDAC8

>1 μM (IC50)

HDAC11

>1 μM (IC50)

HDAC1

>5 μM (IC50)

HDAC2

>5 μM (IC50)

In Vitro

NN-390 exhibits cellular potency with IC50 values of 1.19 μM in MV4-11 cells and 1.38 μM in MM.1S cells while having minimal effects on noncancerous counterparts (IC50 > 50 μM in MRC-9)[1].
NN-390 (72 h) strongly decreases proliferation in HD-MB03 cells, with an IC50 of 0.13 μM, and significantly impairs self-renewal of BTIC-enriched HD-MB03s[1].
NN-390 (0-2 μM, 1 h) markedly increases acetylation of α-tubulin and minimally changes acetylated histone H3[1].
NN-390 (6 h) results in acetylation of α-tubulin from concentrations as low as 0.1 μM (0-0.2 μM), and dose-dependent increases in acetylation of α-tubulin (0-0.2 μM)[1].
NN-390 (0-2 μM, 24 h) promotes cancer cells apoptosis in MV4-11 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Immunofluorescence

Cell Line: HeLa cells[1]
Concentration: 0, 0.1, 0.25, 1, 2 μM
Incubation Time: 1 h
Result: Markedly increased acetylation of α-tubulin and minimally changed acetylated histone H3.

Western Blot Analysis

Cell Line: AML (MV4-11) cells[1]
Concentration: 0, 0.1, 0.5, 1, 5 μM
Incubation Time: 6 h
Result: Resulted in acetylation of α-tubulin from concentrations as low as 0.1 μM and with limited acetylation of histone H3 at only the highest concentration of 5 μM.

Western Blot Analysis

Cell Line: Group 3 MB (HD-MB03) cells[1]
Concentration: 0, 0.053, 0.106, 0.158, 0.211 μM
Incubation Time: 6 h
Result: Dose-dependent increased in acetylation of α-tubulin from the lowest concentration of 53 nM, with no observable change in acetylation of off-target histone H3 up to 211 nM.

Apoptosis Analysis

Cell Line: MV4-11 cells[1]
Concentration: 0, 0.25, 0.75, 1, 2 μM
Incubation Time: 24 h
Result: Promoted cancer cells apoptosis, 39% of cancer cells were undergoing late-stage apoptosis after 18 h at 2 μM, and 11% of cells were in the late apoptosis stage at 0.25 μM.
In Vivo

NN-390 (male CD-1 mice, 20 mg/kg, IP, single dose) increases plasma stability[1].
NN-390 can improve PAMPA (parallel artificial membrane permeability assay)-BBB (blood-brain barrier) score[1].
Pharmacokinetic Parameters of NN-390 in male male CD-1 mice[1].

Compound KT-531 5a; NN-390
t1/2 (h) 1.05 1.90
Cmax (ng/mL) 493 750
AUClast (h*ng/mL) 1576 2523
AUClnf (h*ng/mL) 1519 2548
AUC/D (h*ng/mL) 79 126

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: CD-1 mice (male, n=3)[1]
Dosage: 20 mg/kg
Administration: IP, single dose (Pharmacokinetic Analysis)
Result: Had a half-life of 115 min in human plasma, a 2.8-fold increase in stability.
Molecular Weight

420.38

Formula

C17H16F4N2O4S

CAS No.
SMILES

O=C(NO)C1=CC=C(CN(C(C)C)S(=O)(C2=CC(F)=C(F)C(F)=C2F)=O)C=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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