A-485
A-485 Basic information
- Product Name:
- A-485
- Synonyms:
-
- (1R)-N-[(4-Fluorophenyl)methyl]-2,3-dihydro-5-[[(methylamino)carbonyl]amino]-2',4'-dioxo-N-[(1S)-2,2,2-trifluoro-1-methylethyl]spiro[1H-indene-1,5'-oxazolidine]-3'-acetamide
- A-485
- A485;A 485
- Spiro[1H-indene-1,5'-oxazolidine]-3'-acetamide, N-[(4-fluorophenyl)methyl]-2,3-dihydro-5-[[(methylamino)carbonyl]amino]-2',4'-dioxo-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-, (1R)-
- A-486
- N-(4-Fluorobenzyl)-2-((R)-5-(3-methylureido)-2',4'-dioxo-2,3-dihydrospiro[indene-1,5'-oxazolidin]-3'-yl)-N-((S)-1,1,1-trifluoropropan-2-yl)acetamide
- inhibit,HATs,A 485,Inhibitor,Epigenetic Reader Domain,Histone Acetyltransferase,HAT,A-485,A485
- N-(4-Fluorobenzyl)-2-[(R)-5-(3-methylureido)-2’,4’-dioxo-2,3-dihydrospiro[indene-1,5’-oxazolidin]-3’-yl]-N-[(S)-1,1,1-trifluoro-2-propyl]acetamide
- CAS:
- 1889279-16-6
- MF:
- C25H24F4N4O5
- MW:
- 536.48
- Product Categories:
-
- intermediate
- Mol File:
- 1889279-16-6.mol
A-485 Chemical Properties
- Density
- 1.46±0.1 g/cm3(Predicted)
- storage temp.
- 2-8°C
- solubility
- DMSO:97.41(Max Conc. mg/mL);181.57(Max Conc. mM)
DMF:10.0(Max Conc. mg/mL);18.64(Max Conc. mM)
Ethanol:57.88(Max Conc. mg/mL);107.89(Max Conc. mM)
Ethanol:PBS (pH 7.2) (1:3):0.25(Max Conc. mg/mL);0.47(Max Conc. mM) - form
- A crystalline solid
- pka
- 14.07±0.46(Predicted)
- color
- White to off-white
- optical activity
- [α]/D +40 to +50°, c =0.5 in methanol
- InChIKey
- VRVJKILQRBSEAG-LFPIHBKWSA-N
- SMILES
- [C@@]12(C(=O)N(CC(N(CC3=CC=C(F)C=C3)[C@@H](C)C(F)(F)F)=O)C(=O)O1)C1=C(C=C(NC(NC)=O)C=C1)CC2
A-485 Usage And Synthesis
Uses
A-485 is potent and selective p300/CREB-binding protein (CBP) HAT domain inhibitor (IC50 values are 2.6 and 9.8 nM for the CBP-bromodomain HAT-C/H3 (BHC) and p300-BHC domains, respectively). Displays > 1000-fold selectivity over closely related HATs. Suppresses proliferation in several hematological malignancies and AR+ prostate cancer cell lines in vitro. Inhibits tumor growth in a castration-resistant prostate cancer xenograft model. Orally bioavailable.
Biological Activity
A-485 exhibits an anti-tumor effect and may show therapeutic effects against the growth hormone pituitary adenoma (GHPA). It can specifically block the acetylation of histone H3 lysine 27 (H3K27) and lysine 18 (H3K18) sites catalyzed by p300.', 'A-485 is a potent and selective catalytic inhibitor of the p300 and CREB-binding protein (CBP) histone acetyltransferases (HATs) with an IC50 value of 60 nM. A-485 was most active against haematological malignancies including most multiple myeloma cell lines as well as androgen receptor-positive prostate cancer. It was also shown to inhibit the proliferation of castration-resistant prostate cancer cells and in vivo tumour growth in SCID mice.
in vivo
After tumours are established in SCID male mice, twice daily intraperitoneal injections of A-485 induce 54% tumour growth inhibition after 21 days of dosing (P<0.005 as compare to vehicle control). In addition, in tumour-bearing animals, dosing with A-485 for seven days induces a decrease in the mRNA levels of MYC and the AR-dependent gene SLC45A3 at three hours post-dosing, and (for MYC) a decrease in the protein level, indicating that A-485 inhibits p300-mediated transcriptional activity in vivo. However, at 16 hours post-dosing on the seventh day, A-485 drug levels in the plasma and tumour are decreased as compare to 3 hours. A-485 induces a moderate 9% body weight loss, and the animals recover rapidly upon completion of the A-485 dosing regimen[1].
IC 50
CBP/p300
storage
Store at -20°C
A-485Supplier
- Tel
- 15869524721
- 3525679403@qq.com
- Tel
- 15317229551
- 15151849396@163.com
- Tel
- 0731-13823398 15111215862
- 313359644@qq.com
- Tel
- 18149758185
- sales-cpd@caerulumpharma.com
- Tel
- 15221275939
- shenlinxing@macklin.cn