Name: Abexinostat (PCI-24781)
Brand: Selleck Chemicals
SKU: S1090
Rating: 5 (25 reviews)

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.21%

99.21

Gerelateerde doelwitten	Akt Wnt/beta-catenin PKC HSP ROCK Microtubule Associated Integrin Bcr-Abl Actin FAK
Overig HDAC Inhibitoren	ITF-2357 (Givinostat) Hydrochloride Monohydrate Fimepinostat (CUDC-907) Trichostatin A (TSA) Entinostat (MS-275) RGFP966 Quisinostat (JNJ-26481585) Dihydrochloride Tubastatin A Hydrochloride Tubastatin A Mocetinostat (MGCD0103) Ricolinostat (ACY-1215)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Incubatietijd	Activiteitsbeschrijving	PMID
HeLa	Function assay	2 hrs	Inhibition of dye-labeled tracer binding to HDAC10 (unknown origin) transfected in human HeLa cells measured after 2 hrs by nano-luciferase reporter gene-based BRET assay, IC50=0.007943μM	30964290
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht	397.42	Formule	C₂₁H₂₃N₃O₅	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	783355-60-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	CRA-024781			Smiles	CN(C)CC1=C(OC2=CC=CC=C21)C(=O)NCCOC3=CC=C(C=C3)C(=O)NO

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 80 mg/mL (201.29 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.250mg/ml (0.63mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	0.250mg/ml (0.63mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC₅₀/Ki	HDAC1 (Cell-free assay) 7 nM(Ki) HDAC3/SMRT 8.2 nM(Ki) HDAC6 17 nM(Ki) HDAC2 (Cell-free assay) 19 nM(Ki) HDAC10 24 nM HDAC8 280 nM
In vitro	Abexinostat (PCI-24781) exhibits potent antitumor activity against a variety of tumor cell lines with GI50 ranging from 0.15 μM to 3.09 μM, and also has an antiproliferative effect on HUVEC endothelial cells with GI50 of 0.43 μM. Treatment with this compound 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. 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, it results in a decreased ability to perform homology directed repair of I-SceI-induced chromosome breaks in transfected CHO cells. It induces S phase depletion, G2 cell cycle arrest, and apoptosis in soft tissue sarcoma (STS) cells, and also causes Rad51 transcriptional repression in STS cells potentially mediated via enhanced E2F1 binding to the Rad51 proximal promoter. Additionally, this compound induces caspase and reactive oxygen species-dependent apoptosis through NF-κB mechanisms in Hodgkin lymphoma and non-Hodgkin lymphoma cell lines.
Kinase Assay	HDAC-activiteit
Kinase Assay	HDAC-activiteit wordt gemeten met behulp van een continue, trypsine-gekoppelde test. Voor de karakterisering van de remmer worden metingen uitgevoerd in een reactievolume van 100 μL met behulp van 96-wells assayplaten. Voor elk isozym wordt het HDAC-eiwit in reactiebuffer [50 mM HEPES, 100 mM KCl, 0,001% Tween 20, 5% DMSO (pH 7,4), aangevuld met runder serumalbumine in concentraties van 0% (HDAC1), 0,01% (HDAC2, 3, 8 en 10), of 0,05% (HDAC6)] gemengd met Abexinostat (PCI-24781) in verschillende concentraties en gedurende 15 minuten geïncubeerd. Trypsine wordt toegevoegd tot een uiteindelijke concentratie van 50 nM, en acetyl-Gly-Ala-(N-acetyl-Lys)-AMC wordt toegevoegd tot een uiteindelijke concentratie van 25 μM (HDAC1, 3 en 6), 50 μM (HDAC2 en 10), of 100 μM (HDAC8) om de reactie te starten. Negatieve controlereacties worden uitgevoerd in afwezigheid van deze verbinding in acht replicaten. Reacties worden gemonitord in een fluorescentieplaatlezer. Na een lagtijd van 30 minuten wordt de fluorescentie gedurende een tijdsbestek van 30 minuten gemeten met een excitatiegolflengte van 355 nm en een detectiegolflengte van 460 nm. De toename in fluorescentie met de tijd wordt gebruikt als maat voor de reactiesnelheid. Inhibitieconstanten K_i(app) worden verkregen met behulp van het programma BatchKi.
In vivo	Abexinostat (PCI-24781) was administered at 200 mg/kg once daily every other day (q.o.d.), which significantly inhibited the growth of HCT116 and DLD-1 xenografts in mice by 69% and 59%, respectively. In the HCT116 model, administration of this compound 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) caused inhibition of tumor growth by 48%, 57%, 82.2%, or 80.0%, respectively.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/16731764/ [2] https://pubmed.ncbi.nlm.nih.gov/18042714/ [3] https://pubmed.ncbi.nlm.nih.gov/19417021/ [4] https://pubmed.ncbi.nlm.nih.gov/19417023/

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2025-04-10)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT03600441	ACTIVE_NOT_RECRUITING	Follicular Lymphoma	Xynomic Pharmaceuticals, Inc.	2018-08-27	PHASE2
NCT05698524	RECRUITING	Recurrent High Grade Glioma; Anaplastic Astrocytoma; Anaplastic Oligodendroglioma; Glioblastoma; Gliosarcoma	University of Nebraska	2023-06-26	PHASE1
NCT03592472	RECRUITING	Renal Cell Carcinoma	Xynomic Pharmaceuticals, Inc.	2018-07-17	PHASE3
NCT03936153	RECRUITING	Diffuse Large B-cell Lymphoma (DLBCL)	Xynomic Pharmaceuticals, Inc.	2020-01-20	PHASE2
NCT04498520	WITHDRAWN	Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Hormone Receptor Positive Breast Carcinoma; Locally Advanced Breast Carcinoma; Metastatic Breast Carcinoma; Metastatic Endometrioid Adenocarcinoma; Metastatic Fallopian Tube Carcinoma; Metastatic HER2 Negative Breast Carcinoma; Metastatic Malignant Solid Neoplasm; Metastatic Ovarian Carcinoma; Metastatic Primary Peritoneal Carcinoma; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Refractory Breast Carcinoma; Stage IV Fallopian Tube Cancer AJCC v8; Stage IV Ovarian Cancer AJCC v8; Stage IV Primary Peritoneal Cancer AJCC v8; Stage IV Uterine Corpus Cancer AJCC v8; Stage IVA Fallopian Tube Cancer AJCC v8; Stage IVA Ovarian Cancer AJCC v8; Stage IVA Primary Peritoneal Cancer AJCC v8; Stage IVA Uterine Corpus Cancer AJCC v8; Stage IVB Fallopian Tube Cancer AJCC v8; Stage IVB Ovarian Cancer AJCC v8; Stage IVB Primary Peritoneal Cancer AJCC v8; Stage IVB Uterine Corpus Cancer AJCC v8	Pamela Munster	2021-03-31	PHASE1
NCT03939182	COMPLETED	Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma	Memorial Sloan Kettering Cancer Center	2019-05-29	PHASE1

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Abexinostat (PCI-24781) HDAC Remmer

Molecuulgewicht: 397.42

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Abexinostat (PCI-24781) HDAC Remmer

Molecuulgewicht: 397.42

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkzame concentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo formulatiecalculator (heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Informatie over klinische proeven (Clinical Trial Information)

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)