Name: A-485
Brand: Selleck Chemicals
SKU: S8740
Rating: 5 (49 reviews)

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Quality Control

Batch: Purity: 99.98%

99.98

Related Targets	HDAC JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK
Other p300/CBP Inhibitors	Inobrodib (CCS-1477) Curcumin (Diferuloylmethane) SGC-CBP30 Anacardic Acid CPI-637 E7386 I-CBP112 Histone Acetyltransferase Inhibitor II TTK21 GNE-049

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MOLT3	Function assay	5 μM	48 h	decreased NOTCH3 expression levels	31001470
WM2664	Function assay			H3K27ac IC50=0.6 μM	30266801
SKMEL5	Function assay			H3K27ac IC50=0.9 μM	30266801
A375	Function assay			H3K27ac IC50=1.0 μM	30266801
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	536.48	Formula	C₂₅H₂₄F₄N₄O₅	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1889279-16-6	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC(C(F)(F)F)N(CC1=CC=C(C=C1)F)C(=O)CN2C(=O)C3(CCC4=C3C=CC(=C4)NC(=O)NC)OC2=O

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (186.4 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 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 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 (9.32mM)	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.
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	p300 HAT 0.06 μM
In vitro	A-485 is acetyl-CoA competitive p300/CBP catalytic inhibitor. This compound selectively inhibited proliferation across lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. It inhibited the androgen receptor transcriptional program in both androgen sensitive and castrate resistant prostate cancer. This compound inhibited the activity of the p300-BHC (bromodomain-HAT-C/H3) domain (IC50 = 9.8 nM) as well as CBP-BHC (IC50 = 2.6 nM). It is assayed against other HAT family members and does not inhibit the activity of PCAF, HAT1, MYST3, MYST4, TIP60 and GCN5L2 at 10 µM and is selective over BET bromodomain proteins and >150 non-epigenetic targets. The compound only displayed substantial binding (>90%) to dopamine and serotonin transporters at 10 µM along with modest inhibition of Plk3 (IC50=2.7 µM). As it does not achieve significant brain exposure, it is unlikely to modulate these transporters in vivo. This chemical is selective for p300/CBP over other HATs and histone methyltransferases (HMTs) in cells. It only inhibits H3K27Ac and H3K18Ac. This compound selectively inhibits haematological and prostate cancer cell proliferation and that inhibition of p300/CBP-mediated global histone acetylation does not necessarily translate to an anti-proliferative phenotype. It is primarily metabolised by CYP3A4 in vitro. This chemical also exhibits modest inhibition of CYP2C8 (IC50=0.99 μM) and CYP2C9 (IC50=1.65 μM). There was no activity toward hERG (>30 μM).
In vivo	A-485 displays favourable ADME properties and PK profile. This compound inhibits tumour growth in a castration resistant xenograft model. Treatment of this chemical in LuCaP-77 CR tumour bearing mice tumour induces a decrease in tumour c-Myc protein levels and moderate body weight loss.
References	[1] https://pubmed.ncbi.nlm.nih.gov/28953875/

Applications

Methods	Biomarkers	Images	PMID
Western blot	p27 / FL PARP / C PARP / c-Myc H3K9Ac / H3K18Ac / H3K27Ac		31001470
Growth inhibition assay	Cell viability		31001470

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A-485 p300/CBP Inhibitor

Chemical Structure

Molecular Weight: 536.48