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Formula | C25H24F4N4O5 |
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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) |
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* <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.) |
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. | ||
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Targets |
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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]. |
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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]. |
Cell Assay: |
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Animal Study: |
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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 |
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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.
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