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PCI-24781

PCI-24781 (CRA-024781) is a novel broad spectrum HDAC inhibitor targeting HDAC1, HDAC2, HDAC3, HDAC6, HDAC8 and HDAC10 with K_i of 7 nM, 19 nM, 8.2 nM, 17 nM, 280 nM, 24 nM, respectively.

Catalog No.S1090

3 Reviews 1 Product Citations

: Tel: +1-832-582-8158[email protected]

PCI-24781 Chemical Structure
Molecular Weight: 397.42

Validation & Quality Control

Product Citations(1)

Nat Biotechnol, 2011, 29(3), 255-265

Customer Reviews(3) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

PCI-24781 is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Epigenetics Compound Library (96-well) Inhibitor Library (96-well)

Product Information

Compare HDAC Inhibitors

Research Area
Research Area

Cat.No.	Product Name	Solubility (25°C)
S1053	Entinostat (MS-275, SNDX-275)	<1 mg/mL	75 mg/mL	<1 mg/mL
S1047	Vorinostat (SAHA)	<1 mg/mL	53 mg/mL	3 mg/mL
S1030	Panobinostat (LBH589)	<1 mg/mL	70 mg/mL	<1 mg/mL
S3020	Romidepsin (FK228 ,depsipeptide)	<1 mg/mL	10 mg/mL	<1 mg/mL
S1045	Trichostatin A (TSA)	<1 mg/mL	23 mg/mL	<1 mg/mL
S1122	Mocetinostat (MGCD0103)	<1 mg/mL	13 mg/mL	<1 mg/mL
S2627	Tubastatin A HCl	<1 mg/mL	74 mg/mL	<1 mg/mL
S1085	Belinostat (PXD101)	<1 mg/mL	64 mg/mL	<1 mg/mL
S2170	ITF2357 (Givinostat)	<1 mg/mL	95 mg/mL	3 mg/mL
S1095	LAQ824 (NVP-LAQ824, Dacinostat)	<1 mg/mL	76 mg/mL	<1 mg/mL
S1194	CUDC-101	<1 mg/mL	20 mg/mL	<1 mg/mL
S1515	SB939 (Pracinostat)	<1 mg/mL	72 mg/mL	27 mg/mL
S2012	PCI-34051	<1 mg/mL	59 mg/mL	<1 mg/mL
S1422	Droxinostat	<1 mg/mL	49 mg/mL	49 mg/mL
S1484	MC1568	<1 mg/mL	13 mg/mL	<1 mg/mL
S1090	PCI-24781	<1 mg/mL	80 mg/mL	<1 mg/mL
S1096	JNJ-26481585	<1 mg/mL	79 mg/mL	<1 mg/mL
S1168	Valproic acid sodium salt (Sodium valproate)	33 mg/mL	33 mg/mL	33 mg/mL
S2818	CI994 (Tacedinaline)	<1 mg/mL	≥54 mg/mL	<1 mg/mL
S2244	AR-42 (HDAC-42)	<1 mg/mL	63 mg/mL	63 mg/mL
S2779	M344	<1 mg/mL	62 mg/mL	4 mg/mL
S2759	PI3K/HDAC InhibitorⅠ	<1 mg/mL	102 mg/mL	<1 mg/mL
S8001	Rocilinostat (ACY-1215)	<1 mg/mL	87 mg/mL	<1 mg/mL
S8043	Scriptaid	<1 mg/mL	65 mg/mL	<1 mg/mL
S4125	Sodium Phenylbutyrate	37 mg/mL	8 mg/mL	<1 mg/mL

Combination Therapy

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	PCI-24781 (CRA-024781) is a novel broad spectrum HDAC inhibitor targeting HDAC1, HDAC2, HDAC3, HDAC6, HDAC8 and HDAC10 with K_i of 7 nM, 19 nM, 8.2 nM, 17 nM, 280 nM, 24 nM, respectively.
Targets	HDAC1	HDAC2	HDAC3	HDAC6	HDAC8	HDAC10
IC50	7 nM (K_i)	19 nM (K_i)	8.2 nM (K_i)	17 nM (K_i)	280 nM (K_i)	24 nM (K_i) ^[1]
In vitro	PCI-24781 exhibits potent antitumor activity against a variety of tumor cell lines with GI50 ranging from 0.15 μM to 3.09 μM. PCI-24781 also has an antiproliferative effect on HUVEC endothelial cells with GI50 of 0.43 μM. PCI-24781 treatment causes dose-dependent accumulation of both acetylated histones and acetylated tubulin in HCT116 or DLD-1 cells, induces expression of p21, and leads to PARP cleavage and accumulation of the γH2AX. ^[1] Inhibition of HDAC enzymes by PCI-24781 leads to a significant reduction in the transcription of genes specifically associated with HR, including RAD51. Consistent with inhibition of HR, PCI-24781 treatment results in a decreased ability to perform homology directed repair of I-SceI-induced chromosome breaks in transfected CHO cells. ^[2] PCI-24781 induces S phase depletion, G2 cell cycle arrest, and apoptosis in soft tissue sarcoma (STS) cells. PCI-24781 induces Rad51 transcriptional repression in STS cells potentially mediated via enhanced E2F1 binding to the Rad51 proximal promoter. ^[3] PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-κB mechanisms in Hodgkin lymphoma and non-Hodgkin lymphoma cell lines. ^[4]
In vivo	Administration of PCI-24781 at 200 mg/kg once daily every other day (q.o.d.) significantly inhibits the growth of HCT116 and DLD-1 xenografts in mice by 69% and 59%, respectively. Administration of PCI-24781 at 20 mg/kg, 40 mg/kg, 80 mg/kg, or 160 mg/kg once daily for 4 consecutive days followed by 3 days without treatment each week (q.d. × 4 per week) in the HCT116 model causes inhibition of tumor growth by 48%, 57%, 82.2%, or 80.0%, respectively. ^[1]
Clinical Trials	A Phase I study of PCI-24781 in subjects with lymphoma is currently ongoing.
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

HDAC Activity	HDAC activity is measured using a continuous trypsin-coupled assay. For inhibitor characterization, measurements are done in a reaction volume of 100 μL using 96-well assay plates. For each isozyme, the HDAC protein in reaction buffer [50 mM HEPES, 100 mM KCl, 0.001% Tween 20, 5% DMSO (pH 7.4), supplemented with bovine serum albumin at concentrations of 0% (HDAC1), 0.01% (HDAC2, 3, 8, and 10), or 0.05% (HDAC6)] is mixed with PCI-24781 at various concentrations and allowed to incubate for 15 minutes. Trypsin is added to a final concentration of 50 nM, and acetyl-Gly-Ala-(N-acetyl-Lys)-AMC is added to a final concentration of 25 μM (HDAC1, 3, and 6), 50 μM (HDAC2 and 10), or 100 μM (HDAC8) to initiate the reaction. Negative control reactions are done in the absence of PCI-24781 in replicates of eight. Reactions are monitored in a fluorescence plate reader. After a 30-minute lag time, the fluorescence is measured over a 30-minute time frame using an excitation wavelength of 355 nm and a detection wavelength of 460 nm. The increase in fluorescence with time is used as the measure of the reaction rate. Inhibition constants K_i(app) are obtained using the program BatchKi.

HDAC Activity

HDAC activity is measured using a continuous trypsin-coupled assay. For inhibitor characterization, measurements are done in a reaction volume of 100 μL using 96-well assay plates. For each isozyme, the HDAC protein in reaction buffer [50 mM HEPES, 100 mM KCl, 0.001% Tween 20, 5% DMSO (pH 7.4), supplemented with bovine serum albumin at concentrations of 0% (HDAC1), 0.01% (HDAC2, 3, 8, and 10), or 0.05% (HDAC6)] is mixed with PCI-24781 at various concentrations and allowed to incubate for 15 minutes. Trypsin is added to a final concentration of 50 nM, and acetyl-Gly-Ala-(N-acetyl-Lys)-AMC is added to a final concentration of 25 μM (HDAC1, 3, and 6), 50 μM (HDAC2 and 10), or 100 μM (HDAC8) to initiate the reaction. Negative control reactions are done in the absence of PCI-24781 in replicates of eight. Reactions are monitored in a fluorescence plate reader. After a 30-minute lag time, the fluorescence is measured over a 30-minute time frame using an excitation wavelength of 355 nm and a detection wavelength of 460 nm. The increase in fluorescence with time is used as the measure of the reaction rate. Inhibition constants K_i(app) are obtained using the program BatchKi.

Cell Assay: ^[1]

Cell lines	HCT116, HCT-15, BT-549, NCI-H226, CWR-22RV1, MCF-7, NCI-PC3, DLD-1, SKOV-3, and OVCAR-3
Concentrations	Dissolved in DMSO, final concentrations ~10 μM
Incubation Time	48, 72, 96, or 120 hours
Method	Cells are cultured for at least two doubling times, and growth is monitored at the end of PCI-24781 exposure using an Alamar blue fluorometric cell proliferation assay. PCI-24781 is assayed in triplicate wells in 96-well plates at nine concentrations using half-log intervals ranging from 0.0015 μM to 10 μM. The final DMSO concentration in each well is 0.15%. The concentration required to inhibit cell growth by 50% (GI50) and 95% confidence intervals are estimated from nonlinear regression using a four-parameter logistic equation.

Animal Study: ^[1]

Animal Models	Female BALB/c nu/nu mice implanted s.c. with HCT116 and DLD-1 tumor cells
Formulation	Formulated in 30% HP-cyclodextrin in water
Dosages	~200 mg/kg
Administration	Administered via i.v.

References

Chemical Information

Download PCI-24781 SDF

Molecular Weight (MW)	397.42
Formula	C₂₁H₂₃N₃O₅
CAS No.	783355-60-2
Synonyms	CRA-02478

Solubility (25°C) DMSO 80 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	3-((dimethylamino)methyl)-N-(2-(4-(hydroxycarbamoyl)phenoxy)ethyl)benzofuran-2-carboxamide

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (3)

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Rating

Source

Diabetologia, 2012, 55, 2421–2431. PCI-24781 purchased from Selleck

Method

Analyses of efficacy, potency and IC50

Cell Lines

INS-1 cells

Concentrations

Incubation Time

Results

HC toxin, CI-994, PCI24781 and LAQ824 all protected against cytokine-induced beta cell death, whereas the HDAC8-selective inhibitor PCI34051 showed no protection.

Click to enlarge

Rating

Source

Diabetologia, 2012, 55(9), 2421-31.. PCI-24781 purchased from Selleck

Method

Cell viability assay

Cell Lines

INS-1 cells

Concentrations

16-80 h

Incubation Time

Results

CI-994, PCI24781 and LAQ824 all protected against cytokine-induced beta cell death, whereas the HDAC8-selective inhibitor PCI34051 showed no protection.

Click to enlarge

Rating

Source

Nature Biotechnology , 2011, 29, 255-265. PCI-24781 purchased from Selleck

Method

Immunofluorescence

Cell Lines

K562 cells

Concentrations

2 μM

Incubation Time

6 h

Results

The nonselective HDAC inhibitors (SAHA, PCI-24781) increased steady-state acetylation of tubulin and histones manifested by the staining of acetylated microtubules and punctuate nuclear staining of acetylated histones. The class I selective HDAC inhibitors stimulated histone acetylation but did not affect tubulin.

Product Citations (1)

Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. [Bantscheff M, et al. Nat Biotechnol 2011;29(3), 255-265]
PubMed: 21258344

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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PCI-24781