SB939(Pracinostat) | Adrenergic Receptor Inhibitor | Buy SB939(Pracinostat) from supplier selleckchem.com

Information	SB939 (Pracinostat) is a potent HDAC inhibitor of HDACs class I, II and IV with K_i of 19 to 48 nM, 16 to 247 nM, and 43 nM, with the exception of HDAC6.
Targets	HDACs I	HDACs II (except HDAC6)	HDACs IV
IC50	19 to 48 nM (K_i)	16 to 247 nM (K_i)	43 nM (K_i) ^[1]
In vitro	SB939 had no activity against the class III isoenzyme SIRT I. SB939 is more sensitive to cutaneous T-cell lymphoma cells and leukemia cells, with IC50 from 50 nM (H9 cutaneous T-cell lymphoma cells) to 170 nM (HEL92.1.7 erythroleukemia cells), compared to colon and prostate cancer cell lines. SB939 has no inhibitory to normal human dermal fibroblasts at concentrations up to 100 μM. SB939 induces acetylated (K9/K14) histone H3, acetylation of α-tubulin, decreased retinoblastoma serine phosphorylation on S807/811 and induction of cell cycle arrest in HCT-116 cells. ^[1]
In vivo	SB939 has greater pharmacokinetic properties and oral bioavailability than SAHA in nude mice. SB939 selectively accumulates in tumor tissue in HCT-116 xenografts with dosed of 50 mg/kg. SB939 shows great antitumor activity with 94% TGI in HCT-116 tumor-bearing mice at 100 mg/kg. Furthermore, in APC^min mice, SB939 inhibits adenoma formation, hemocult scores, and increased hematocrit values more effectively than 5-fluorouracil. ^[1] SB939 also has broad antitumor activity and highly efficacious in tumor models (HCT-116, PC-3, A2780, MV4-11, Ramos). SB939 has high and dose-proportional oral exposures and very good ADME (absorption, distribution, metabolism, and excretion), safety, and pharmaceutical properties. ^[2]
Clinical Trials	SB939 is currently in Phase II clinical trial in patients with translocation-associated recurrent/metastatic sarcomas.
Features	SB939 is Singapore's first locally developed anti-cancer compound to enter Phase I clinical trials.

Information

SB939 (Pracinostat) is a potent HDAC inhibitor of HDACs class I, II and IV with K_i of 19 to 48 nM, 16 to 247 nM, and 43 nM, with the exception of HDAC6.

Targets

HDACs I

HDACs II (except HDAC6)

HDACs IV

IC50

19 to 48 nM (K_i)

16 to 247 nM (K_i)

43 nM (K_i) ^[1]

In vitro

SB939 had no activity against the class III isoenzyme SIRT I. SB939 is more sensitive to cutaneous T-cell lymphoma cells and leukemia cells, with IC50 from 50 nM (H9 cutaneous T-cell lymphoma cells) to 170 nM (HEL92.1.7 erythroleukemia cells), compared to colon and prostate cancer cell lines. SB939 has no inhibitory to normal human dermal fibroblasts at concentrations up to 100 μM. SB939 induces acetylated (K9/K14) histone H3, acetylation of α-tubulin, decreased retinoblastoma serine phosphorylation on S807/811 and induction of cell cycle arrest in HCT-116 cells. ^[1]

In vivo

SB939 has greater pharmacokinetic properties and oral bioavailability than SAHA in nude mice. SB939 selectively accumulates in tumor tissue in HCT-116 xenografts with dosed of 50 mg/kg. SB939 shows great antitumor activity with 94% TGI in HCT-116 tumor-bearing mice at 100 mg/kg. Furthermore, in APC^min mice, SB939 inhibits adenoma formation, hemocult scores, and increased hematocrit values more effectively than 5-fluorouracil. ^[1] SB939 also has broad antitumor activity and highly efficacious in tumor models (HCT-116, PC-3, A2780, MV4-11, Ramos). SB939 has high and dose-proportional oral exposures and very good ADME (absorption, distribution, metabolism, and excretion), safety, and pharmaceutical properties. ^[2]

Clinical Trials

SB939 is currently in Phase II clinical trial in patients with translocation-associated recurrent/metastatic sarcomas.

Features

SB939 is Singapore's first locally developed anti-cancer compound to enter Phase I clinical trials.

HDAC enzyme assay	For in vitro studies, SB939 is dissolved in DMSO (stock concentration, 10 mM). The HDAC enzyme assay for class I, II and IV isoenzymes is performed in black 384-well plates using the fluorescent-based HDAC activity assay. The reaction contained 2.5 or 5 μL of the HDAC isoenzyme, assay buffer (25 mM Tris-HCl, pH 7.5; 137 mM NaCl; 2.7 mM KCl, 1 mM MgCl₂ and 1 mg/mL BSA), different concentrations of SB939 or DMSO, and the fluorogenic deacetylase substrate Flour de Lys^TM in a total reaction volume of 33 μL. The concentration of substrate used in the reaction varied according to the isoenzyme used (50 μM for HDAC6, 250 μM for HDACs 2-5 and 11 or 625 μM for HDAC1 and HDACs 7-10). After 2 hours incubation at room temperature 16 μL of Flour de Lys^TM developer are added and a fluorophore is generated where substrate deacetylation has occured. The emitted light is measured (at 460 nm) in a microplate reader after additional 10 min of incubation (excitation 360 nm). IC50 values are generated using the XLfit software, K_i values are obtained using the Cheng-Prusoff equation: IC50/(1+[concentration of the subs trate]/ K_m).

Cell lines:	Colo205, HCT-116, A2780, PC3, A2780, DU145, MCF7, BT549, MDA-MB231, T47D, NHI-H460, A549 cells and etc.
Concentrations:	1.5 nM to 100 μM.
Incubation Time:	96 hours
Method:	Cells are seeded in 96-well plates at a predetermined optimal density, in the log growth phase, and rested for 24 hours (adherent cells) or 2 hours (suspension cells), respectively, before treatment with SB939. All experiments are done for 96 hours, with 1% solvent, using either the CyQUANT Cell proliferation assay kit for adherent cells or the CellTiter96 Aqueous One solution cell proliferation kit for suspension cells, according to the manufacturer's instructions, in a total volume of 100 μL with SB939 concentrations from 100 μM to 1.5 nM. IC50 are determined using the XLfit software.

Cell lines:

Colo205, HCT-116, A2780, PC3, A2780, DU145, MCF7, BT549, MDA-MB231, T47D, NHI-H460, A549 cells and etc.

Concentrations:

1.5 nM to 100 μM.

Incubation Time:

96 hours

Method:

Cells are seeded in 96-well plates at a predetermined optimal density, in the log growth phase, and rested for 24 hours (adherent cells) or 2 hours (suspension cells), respectively, before treatment with SB939. All experiments are done for 96 hours, with 1% solvent, using either the CyQUANT Cell proliferation assay kit for adherent cells or the CellTiter96 Aqueous One solution cell proliferation kit for suspension cells, according to the manufacturer's instructions, in a total volume of 100 μL with SB939 concentrations from 100 μM to 1.5 nM. IC50 are determined using the XLfit software.

Animal Models:	HCT-116 xenograft models are established in female BALB/c nude mice.
Formulation:	SB939 is prepared in 0.5% methylcellulose (w/v) and 0.1% Tween-80 in water for oral dosing. For pharmacokinetic analysis, SB939 is dissolved in normal saline for i.v. injection.
Dosages:	25, 50, 75, or 100 mg/kg
Administration:	Administered by oral gavage or i.v. injection

Animal Models:

HCT-116 xenograft models are established in female BALB/c nude mice.

Formulation:

SB939 is prepared in 0.5% methylcellulose (w/v) and 0.1% Tween-80 in water for oral dosing. For pharmacokinetic analysis, SB939 is dissolved in normal saline for i.v. injection.

Dosages:

25, 50, 75, or 100 mg/kg

Administration:

Administered by oral gavage or i.v. injection

Molecular Weight (WM):	358.48
Formula:	C₂₀H₃₀N₄O₂
CAS No.:	929016-96-6
Synonyms:	N/A

Molecular Weight (WM):

358.48

Formula:

C₂₀H₃₀N₄O₂

CAS No.:

929016-96-6

Synonyms:

N/A

Dissolve in (25°C):	DMSO ≥72mg/mL
	Water <1mg/mL
	Ethanol ≥72mg/mL
Storage:	2 years-20°CPowder
	1 week-4°Cin DMSO
	1 month-80°in DMSO

SB939 (Pracinostat)

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Biological Activity

Protocol (Only for Reference)

Kinase Assay: [1]

Cell Assay: [1]

Animal Study:[1]

References

Chemical Information

Quality Control & MSDS

Research Area

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Loading Control Antibodies

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Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study:^[1]

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