Name: Apabetalone (RVX-208)
Brand: Selleck Chemicals
SKU: S7295
Rating: 5 (22 reviews)

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Controllo Qualità

Lotto: Purezza: 99.85%

99.85

Target correlati	HDAC JAK Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK Histone Acetyltransferase
Altro BET Inibitori	Pelabresib (CPI-0610) ZEN-3694 (BET-IN-19) Molibresib (I-BET-762) Mivebresib (ABBV-075) INCB054329 Birabresib (OTX015) I-BET151 (GSK1210151A) AZD5153 6-hydroxy-2-naphthoic acid CPI-203 I-BRD9

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Formulazione	Descrizione dellattività	PMID
HepG2	Function assay	~60 μM		DMSO	induces apoA-I mRNA and de novo synthesis of apoA-I.	20513599
U2OS	Function assay	~5 μM			displaces BET proteins from chromatin	24248379
BL21(DE3)-R3-pRARE2	Function assay				Inhibition of recombinant human His6-tagged BRD4 bromodomain 2 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells preincubated for 30 mins followed by HSGRGK(Ac)GGK(Ac)GLGK(Ac)GGAK(Ac)RHRK(Biotin)-OH peptide substrate addition after 30 mins by alphas, Kd = 0.135 μM.	28195723
BL21(DE3)	Function assay				Binding affinity to human BRD4 bromodomain 2 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry, Kd = 0.14 μM.	26367539
BL21(DE3)-R3-pRARE2	Function assay				Inhibition of recombinant human His6-tagged BRD3 bromodomain 2 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells, Kd = 0.195 μM.	28195723
BL21(DE3)	Function assay				Binding affinity to human BRD2 bromodomain 2 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry, Kd = 0.25 μM.	26367539
BL21(DE3)-R3-pRARE2	Function assay				Inhibition of recombinant human His6-tagged BRD2 bromodomain 2 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells, Kd = 0.251 μM.	28195723
BL21(DE3)	Function assay				Binding affinity to human BRD4 bromodomain 1 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry, Kd = 1.1 μM.	26367539
BL21(DE3)-R3-pRARE2	Function assay				Inhibition of recombinant human His6-tagged BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells preincubated for 30 mins followed by H4K5acK8acK12acK16ac peptide substrate addition after 30 mins by alphascreen assay, Kd = 1.142 μM.	28195723
SAE	Function assay		24 hrs		Inhibition of BRD4 in human SAE cells assessed as reduction in TLR3 agonist poly(I:C) -induced ISG54 RNA expression preincubated for 24 hrs followed by poly(I:C) addition and measured after 4 hrs by SYBR green dye-based qRT-PCR analysis, IC50 = 2.63 μM.	29649741
SAE	Function assay		24 hrs		Inhibition of BRD4 in human SAE cells assessed as reduction in TLR3 agonist poly(I:C) -induced ISG56 RNA expression preincubated for 24 hrs followed by poly(I:C) addition and measured after 4 hrs by SYBR green dye-based qRT-PCR analysis, IC50 = 2.74 μM.	29649741
SAE	Function assay		24 hrs		Inhibition of BRD4 in human SAE cells assessed as reduction in TLR3 agonist poly(I:C) -induced grobeta RNA expression preincubated for 24 hrs followed by poly(I:C) addition and measured after 4 hrs by SYBR green dye-based qRT-PCR analysis, IC50 = 3.73 μM.	29649741
SAE	Function assay		24 hrs		Inhibition of BRD4 in human SAE cells assessed as reduction in TLR3 agonist poly(I:C) -induced IL-8 RNA expression preincubated for 24 hrs followed by poly(I:C) addition and measured after 4 hrs by SYBR green dye-based qRT-PCR analysis, IC50 = 3.85 μM.	29649741
BL21(DE3)-R3-pRARE2	Function assay				Inhibition of recombinant human His6-tagged BRD3 bromodomain 1 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells, Kd = 4.065 μM.	28195723
MV4-11	Antiproliferative assay		72 hrs		Antiproliferative activity against human MV4-11 cells after 72 hrs by MTT assay, IC50 = 4.48 μM.	28765013
BL21(DE3)-R3-pRARE2	Function assay				Inhibition of recombinant human His6-tagged BRD2 bromodomain 1 expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells, Kd = 5.78 μM.	28195723
BL21(DE3)	Function assay				Binding affinity to human BRD2 bromodomain 1 expressed in Escherichia coli BL21 (DE3) cells by isothermal titration calorimetry, Kd = 5.8 μM.	26367539
OCI-AML3	Antiproliferative assay		72 hrs		Antiproliferative activity against human OCI-AML3 cells after 72 hrs by MTT assay, IC50 = 7.17 μM.	28765013
OCI-AML2	Antiproliferative assay		72 hrs		Antiproliferative activity against human OCI-AML2 cells after 72 hrs by MTT assay, IC50 = 8.31 μM.	28765013
MCF7	Autophagy assay	150 uM			Induction of autophagy in human MCF7 cells assessed as downregulation of p62/SQSTM1 expression at 150 uM by Western blot analysis	29172540
MDA-MB-231	Autophagy assay	150 uM			Induction of autophagy in human MDA-MB-231 cells assessed as downregulation of p62/SQSTM1 expression at 150 uM by Western blot analysis	29172540
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Informazioni chimiche, conservazione e stabilità

Peso molecolare	370.4	Formula	C₂₀H₂₂N₂O₅	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	1044870-39-4	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	RVX-000222			Smiles	CC1=CC(=CC(=C1OCCO)C)C2=NC3=C(C(=CC(=C3)OC)OC)C(=O)N2

Solubilità

In vitro
Lotto:

DMSO : 74 mg/mL (199.78 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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.
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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Caratteristiche	First-in-class BD2-selective inhibitor of BET bromodomain and has been tested in Phase II clinical trials for treatment of coronary syndromes and atherosclerosis.
Targets/IC₅₀/Ki	BD2 (Cell-free assay) 0.51 μM
In vitro	Apabetalone (RVX-208), un inibitore di BET bromodomain, si lega preferenzialmente al secondo bromodominio presente sulle proteine BET. Come stimolatore dell'espressione genica dell'apolipoproteina (APO) AI, aumenta l'apoA-I e l'HDL-C in vitro.
In vivo	Apabetalone (RVX-208) aumenta significativamente l'apoA-I sierica e l'HDL-C negli AGM e migliora l'efflusso di colesterolo tramite diverse vie.
Riferimenti	[1] https://pubmed.ncbi.nlm.nih.gov/24248379/ [2] https://pubmed.ncbi.nlm.nih.gov/20178050/ [3] https://pubmed.ncbi.nlm.nih.gov/20513599/

Applicazioni

Metodi	Biomarcatori	Immagini	PMID
Western blot	p21 / p24 / β-actin cyclin D1 / CDK4 / CDK6 / p24 / β-actin Rb / p-Rb(S780) / p-Rb(S795) / p-Rb(S807/811) / β-actin Cyclin T1 / CDK9-55kDa / CDK9-42kDa / p-CDK9 / CTD / CTD-Ser2P / p24 / β-actin Phospho-RelA / Total-RelA / Actin / BRD2 / α-Tubulin		29789664
Immunofluorescence	monocyte adhesion DNA SARS-CoV-2 CTNT		31300040

Informazioni sullo studio clinico

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
NCT03160430	Not yet recruiting	Kidney Failure Chronic	Resverlogix Corp	November 22 2024	Phase 1\|Phase 2
NCT03228940	Withdrawn	Fabry Disease	Resverlogix Corp	November 22 2022	Phase 1\|Phase 2
NCT01863225	Terminated	Dyslipidemia\|Coronary Artery Disease	Resverlogix Corp\|South Australian Health and Medical Research Institute	May 2013	Phase 2
NCT01728467	Completed	Diabetes	Resverlogix Corp\|Baker Heart and Diabetes Institute\|Nucleus Network Ltd	November 2012	Phase 2
NCT01067820	Completed	Coronary Artery Disease	Resverlogix Corp\|The Cleveland Clinic	September 2011	Phase 2
NCT01423188	Completed	Coronary Artery Disease\|Dyslipidemia	Resverlogix Corp\|The Cleveland Clinic	August 2011	Phase 2

Supporto tecnico

Istruzioni per la manipolazione

Tel: +1-832-582-8158 Ext:3

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C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Apabetalone (RVX-208) BET inibitore

Struttura chimica

Peso molecolare: 370.4