A-485

製品コードS8740 バッチS874002

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C25H24F4N4O5
分子量 536.48 CAS No. 1889279-16-6
Solubility (25°C)* 体外 DMSO 100 mg/mL (186.4 mM)
Ethanol 100 mg/mL (186.4 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro

A-485 is acetyl-CoA competitive p300/CBP catalytic inhibitor. This compound selectively inhibited proliferation across lineage-specific tumor types, including several hematological 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 hematological 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 metabolized 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)[1].
in vivo

A-485 displays favorable ADME properties and PK profile. This compound inhibits tumor growth in a castration resistant xenograft model. Treatment of this chemical in LuCaP-77 CR tumor bearing mice tumor induces a decrease in tumor c-Myc protein levels and moderate body weight loss[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HeLa cells
濃度 10 μM
反応時間 16 h
実験の流れ

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.
動物実験 動物モデル LuCap-77 CR xenograft tumors (established in SCID mice)
投薬量 100 mg/kg
投与方法 i.p.

参考

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
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
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
VGLL2 and TEAD1 fusion proteins identified in human sarcoma drive YAP/TAZ-independent tumorigenesis by engaging EP300 [ Elife, 2025, 13RP98386] PubMed: 40338073
Valemetostat-SAHA-Driven Acetylation of p53 via SET/TAF-Iβ Displacement and p300 Activation Modulates Cell Cycle Regulators in Pancreatic Cancer Cells [ Biomedicines, 2025, 13(9)2279] PubMed: 41007839

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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