A-485

Catalog No.S8740 Batch:S874003

Technical Data

Formula

C₂₅H₂₄F₄N₄O₅

Molecular Weight

536.48

CAS No.

1889279-16-6

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (186.4 mM)

Ethanol

100 mg/mL (186.4 mM)

Water

Insoluble

In Vivo (Add solvents to the product individually and in order.)

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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

A-485 is a potent, selective and drug-like p300/CBP catalytic inhibitor with an IC50 of 0.06 μM for p300 HAT. It is selective over BET bromodomain proteins and >150 non-epigenetic targets.

Targets

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 tumor 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.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell Lines HeLa cells Concentrations 10 μM Incubation Time 16 h Method HeLa cells were SILAC labeled with heavy isotopes of arginine and lysine. The cells were treated with A-485 (10 μM) or vehicle control for 16 hours. Cell were lysed in ice-cold lysis buffer [50 mM Hepes, pH7.5, 150 mM NaCl, 1 mM EDTA, 1% NP-40, 0.1% sodium deoxycholate, 1x complete protease inhibitor cocktail]. Proteins were proteolyzed with trypsin, and acetylated peptides were analyzed.
Animal Study:^{^[1]}	Animal Models LuCap-77 CR xenograft tumors (established in SCID mice) Dosages 100 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell Lines
HeLa cells
Concentrations
10 μM
Incubation Time
16 h
Method
HeLa cells were SILAC labeled with heavy isotopes of arginine and lysine. The cells were treated with A-485 (10 μM) or vehicle control for 16 hours. Cell were lysed in ice-cold lysis buffer [50 mM Hepes, pH7.5, 150 mM NaCl, 1 mM EDTA, 1% NP-40, 0.1% sodium deoxycholate, 1x complete protease inhibitor cocktail]. Proteins were proteolyzed with trypsin, and acetylated peptides were analyzed.

Animal Study:^{^[1]}

Animal Models
LuCap-77 CR xenograft tumors (established in SCID mice)
Dosages
100 mg/kg
Administration
i.p.

References

https://pubmed.ncbi.nlm.nih.gov/28953875/

Sellecks A-485 Has Been Cited by 45 Publications

Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer [ Nat Genet, 2025, 57(10):2468-2481]	PubMed: 41044247
DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming [ Cancer Discov, 2025, 15(2):382-400]	PubMed: 39326063
α-Ketoglutarate promotes trophectoderm induction and maturation from naive human embryonic stem cells [ Nat Cell Biol, 2025, 10.1038/s41556-025-01658-1]	PubMed: 40269259
ACSS2 mediates an epigenetic pathway to regulate β-cell adaptation during gestation in mice [ Nat Commun, 2025, 16(1):4697]	PubMed: 40393969
The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis [ Nat Commun, 2025, 16(1):7483]	PubMed: 40796740
Mapping the nuclear landscape with multiplexed super-resolution fluorescence microscopy [ Nat Commun, 2025, 16(1):6042]	PubMed: 40593784
The ESCRT protein CHMP5 promotes T cell leukemia by enabling BRD4-p300-dependent transcription [ Nat Commun, 2025, 16(1):4133]	PubMed: 40319015
Extracellular Histones as Exosome Membrane Proteins Regulated by Cell Stress [ J Extracell Vesicles, 2025, 14(2):e70042]	PubMed: 39976275
Lactate-mediated histone lactylation promotes melanoma angiogenesis via IL-33/ST2 axis [ Cell Death Dis, 2025, 16(1):701]	PubMed: 41053006
DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity [ Cell Rep, 2025, 44(4):115544]	PubMed: 40202846

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.