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ARV-825 PROTAC chemical

Name: ARV-825
Brand: Selleck Chemicals
SKU: S8297
Availability: InStock
Rating: 5 (9 reviews)

Cat.No.S8297

ARV-825 is a BRD4 Inhibitor that recruits BRD4 to the E3 ubiquitin ligase cereblon, leading to fast, efficient, and prolonged degradation of BRD4 and sustained down-regulation of MYC.

Chemical Structure

Molecular Weight: 923.43

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability

Quality Control

Batch: Purity: 99.45%

99.45

Related Targets	Epigenetic Reader Domain HDAC JAK Histone Methyltransferase AMPK PKC PARP HIF Histone Acetyltransferase Aurora Kinase Sirtuin PRMT Histone Demethylase EZH1/2 DNA Methyltransferase Pim LSD1 MLL JMJD G9a/GLP NSD FTO MicroRNA PAD SETD SMYD DOT1 COMT WDR5 HNMT
Related Products	dBET6 dBET1 ACBI1 ARV-771 TD-165 A1874 YD23 TL12-186 GMB-475 Luxdegalutamide (ARV-766) ARV-393 Setidegrasib (ASP3082) EGNHS

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
22RV1	Function assay		24 hrs	Induction of CRBN-mediated BRD4 degradation in human 22RV1 cells measured after 24 hrs by immunoblotting analysis, DC50 = 0.00057 μM.	30684871
NAMALWA	Function assay		overnight	Protac activity at Cereblon/BRD4 in human NAMALWA cells assessed as induction of BRD4 protein degradation in human NAMALWA cells after overnight incubation by immunoblot method, DC50 = 0.001 μM.	31047748
CA46	Function assay		overnight	Protac activity at Cereblon/BRD4 in human CA46 cells assessed as induction of BRD4 protein degradation in human CA46 cells after overnight incubation by immunoblot analysis, DC50 = 0.001 μM.	31047748
MV4-11	Growth inhibition assay		96 hrs	Growth inhibition of human MV4-11 cells after 96 hrs by CCK8 assay, IC50 = 0.00105 μM.	30019901
RS4:11	Cytotoxicity assay		4 days	Cytotoxicity against human RS4:11 cells assessed as cell growth inhibition after 4 days by WST-8 assay, IC50 = 0.0033 μM.	28339196
RS4:11	Growth inhibition assay		96 hrs	Growth inhibition of human RS4:11 cells after 96 hrs by CCK8 assay, IC50 = 0.0033 μM.	30019901
MV4-11	Antiproliferative assay		48 hrs	Antiproliferative activity against human MV4-11 cells after 48 hrs by CellTiter-Glo luminescent cell viability assay, EC50 = 0.01698 μM.	28595007
MOLM13	Cytotoxicity assay		4 days	Cytotoxicity against human MOLM13 cells assessed as cell growth inhibition after 4 days by WST-8 assay, IC50 = 0.0182 μM.	28339196
MOLM13	Growth inhibition assay		96 hrs	Growth inhibition of human MOLM13 cells after 96 hrs by CCK8 assay, IC50 = 0.0182 μM.	30019901
HL60	Antiproliferative assay		48 hrs	Antiproliferative activity against human HL60 cells after 48 hrs by CellTiter-Glo luminescent cell viability assay, EC50 = 0.03467 μM.	28595007
RS4:11	Function assay	3 to 30 nM	3 hrs	Induction of cereblon/cullin 4A-mediated BRD2 degradation in human RS4:11 cells at 3 to 30 nM after 3 hrs by Western blot method	28339196
RS4:11	Function assay	3 to 30 nM	3 hrs	Induction of cereblon/cullin 4A-mediated BRD3 degradation in human RS4:11 cells at 3 to 30 nM after 3 hrs by Western blot method	28339196
RS4:11	Function assay	3 to 30 nM	3 hrs	Induction of cereblon/cullin 4A-mediated BRD4 degradation in human RS4:11 cells at 3 to 30 nM after 3 hrs by Western blot method	28339196
U266	Function assay		12 hrs	Induction of CRBN-mediated BRD4 degradation in human U266 cells up to 1000 nM measured after 12 hrs by immunoblotting analysis	30684871
U266	Function assay		12 hrs	Induction of CRBN ubiquitin ligase-mediated IKZF1 degradation in human U266 cells up to 1000 nM measured after 12 hrs by immunoblotting analysis	30684871
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	923.43	Formula	C₄₆H₄₇ClN₈O₉S	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1818885-28-7	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)OCCOCCOCCOCCNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)C8=CC=C(C=C8)Cl)C

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (108.29 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 6 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

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.
Clear solution	5%DMSO 1 Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	7.500mg/ml (8.12mM)	Taking the 1 mL working solution as an example, add 50 μL of 150 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.
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 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (5.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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 make it clear; 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.
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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	BRD4 BD2 ^[1] (Cell-free assay) 28 nM(Kd) BRD4 BD1 ^[1] (Cell-free assay) 90 nM(Kd)
In vitro	Compared with the BRD4 inhibitors, ARV-825 treatment results in a strikingly more pronounced effect on the levels of c-MYC, and downstream cell proliferation and apoptosis induction in BL (Burkitt’s Lymphoma) cell lines^[1]. The IC50s of this compound for all tested cell lines and primary AML cells at 72 hours are in the low nanomolar range (2-50 nM). This treatment reduces PIM1 levels and phosphorylation of CXCR4 in AML cells while overexpression of PIM1 or Myc reverses the phenomena^[3].
In vivo	In a mouse model of human leukemia, the leukemia burdens are significantly lower in the ARV-825 treated mice as confirmed by luciferase imaging, flow cytometry, spleen size and survived longer compared to control mice^[3].
References	[1] https://pubmed.ncbi.nlm.nih.gov/26051217/ [2] https://pubmed.ncbi.nlm.nih.gov/28339196/ [3] http://www.bloodjournal.org/content/128/22/748?sso-checked=true [4] https://pubmed.ncbi.nlm.nih.gov/30903020/

Applications

Methods	Biomarkers	PMID
Western blot	BRD1 / BRD2 / BRD3 / BRD4 / p21 c-MYC PARP / cleaved PARP CDK6 / CDK4 cleaved caspase 9 / cleaved caspase 3 Akt / pAKT-S473 / mTOR / p-mTOR-S2448 / p70S6K / p70S6K-T389 / 4EBP1/ p-4EBP1-S65 / PDK1 / p-PDK1-S241 / PI3K / p-PI3K-T458 JAK2 / p-STAT5 / p-STAT3 / PIM1 / p27 / Bcl-xl / γH2AX	30903020
Immunofluorescence	BRD4	28042144
Growth inhibition assay	Cell viability	26051217

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