A-485

製品コードS8740 バッチS874003

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）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml 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.

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. A-485 selectively inhibited proliferation across lineage-specific tumor types, including several hematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen sensitive and castrate resistant prostate cancer. A-485 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). A-485 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 A-485 does not achieve significant brain exposure, it is unlikely to modulate these transporters in vivo. A-485 is selective for p300/CBP over other HATs and histone methyltransferases (HMTs) in cells. It only inhibits H3K27Ac and H3K18Ac. A-485 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. A-485 is primarily metabolized by CYP3A4 in vitro. A-485 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. A-485 inhibits tumor growth in a castration resistant xenograft model. Treatment of A-485 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.

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：

Single-molecule chromatin configurations link transcription factor binding to expression in human cells [ bioRxiv, 2024, 2024.02.02.578660] PubMed: 38352517
PAX3-FOXO1 uses its activation domain to recruit CBP/P300 and shape RNA Pol2 cluster distribution [ Nat Commun, 2023, 14(1):8361] PubMed: 38102136
Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell [ Gut Microbes, 2023, 15(2):2249143] PubMed: 37635362
Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell [ Gut Microbes, 2023, 15(2):2249143] PubMed: 37635362
PASK links cellular energy metabolism with a mitotic self-renewal network to establish differentiation competence [ Elife, 2023, 12e81717] PubMed: 37052079
Histone acetyltransferase P300 deficiency promotes ferroptosis of vascular smooth muscle cells by activating the HIF-1α/HMOX1 axis [ Mol Med, 2023, 29(1):91] PubMed: 37415103
Acetylated-PPARγ expression is regulated by different P53 genotypes associated with the adipogenic differentiation of polyploid giant cancer cells with daughter cells [ Cancer Biol Med, 2023, 20(1):56-76] PubMed: 36647790
Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantification of the acetyl-coenzyme A competitive p300/CBP catalytic inhibitor A-485 in biological samples [ Biomed Chromatogr, 2023, e5819.] PubMed: 38148286
Genome folding principles revealed in condensin-depleted mitotic chromosomes [ bioRxiv, 2023, 2023.11.09.566494] PubMed: 38014261
CRISPR-ChIP delineates a Menin-dependent oncogenic DOT1L complex in MLL-leukaemia [ bioRxiv, 2023, 10.1101/2023.03.17.533231] PubMed: None

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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