A-485

• CAS: 1889279-16-6
• Catalog Number: ACM1889279166
• Category: Inhibitors
• Molecular Weight: 536.48
• Molecular Formula: C25H24F4N4O5
• Description: A-485 is a potent and selective HAT inhibitor of p300/CBP in vitro with an IC50 of 10 nM in a p300 TR-FRET assay and 3 nM in a CBP TR-FRET assay with selectivity > 1000-fold over closely related HATs. SPR data indicates potent binding to p300 (KD=15 nM). In PC-3 cells A-485 reduces H3K27ac with IC50 of 73 nM while not affecting H3K9ac levels. Inhibition of cellular proliferation is observed in several cancer cell types, most notably AR+ prostate, multiple myeloma, and NHL. A-486 is a suitable control with 1000-fold higher IC50 in the p300 TR-FRET assay.
• Synonyms: A-485; A 485; A485
• IUPAC Name: 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
• Canonical SMILES: O=C(N1CC(N([C@H](C(F)(F)F)C)CC2=CC=C(F)C=C2)=O)[C@@]3(OC1=O)CCC4=CC(NC(NC)=O)=CC=C43
• InChI: InChI=1S/C25H24F4N4O5/c1-14(25(27,28)29)32(12-15-3-5-17(26)6-4-15)20(34)13-33-21(35)24(38-23(33)37)10-9-16-11-18(7-8-19(16)24)31-22(36)30-2/h3-8,11,14H,9-10,12-13H2,1-2H3,(H2,30,31,36)/t14-,24+/m0/s1
• InChI Key: VRVJKILQRBSEAG-LFPIHBKWSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: A-485 is a catalytic inhibitor of p300/CBP with IC50s of 9.8 nM and 2.6 nM for p300 and CBP histone acetyltransferase (HAT), respectively.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 55.97; H, 4.51; F, 14.17; N, 10.44; O, 14.91
• Exact Mass: 536.1683
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: Consistent with immunoblotting data (Figure 4), A-485 reduces overall H3K27ac peak intensity in MCF-7 cells (Figure 5A,B). In analyzing the ChIP-seq dataset, this study divided the H3K27ac peaks into four groups (peak types): All Peaks (AP, all detected peaks), Lost Peaks (LP, DMSO unique peaks), Shared Peaks (SP, peaks detected in both DMSO and A-485), and Gained Peaks (GP, A-485 unique peaks) (Figure 5A). In total, 36,352 H3K27ac peaks are detected, among which the number of LPs and SPs is similar, while there are fewer GPs (~8000). A-485 markedly reduces H3K27ac peak intensity in LPs but only has a small effect on SPs (Figure 5B).; Reference: Cancers (Basel). 2021 Jun; 13(11): 2799. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200112/
• In Vivo Activity: To investigate the in vivo metabolic properties of A-485, 8-week-old C57BL/6 mice fed with NCD were intraperitoneally administrated with A-485 (20 mg · kg-1 · day-1) for 1 week. A-485-administered mice displayed significantly lower body weight compared with vehicle-administered mice after treatment for 3 days (Fig. 1a). However, food intake was comparable between vehicle- and A-485-administered mice (Fig. S1a). No significant changes were observed for the oxygen consumption (VO2), carbon dioxide (VCO2) production, and respiratory exchange ratios (RER) in mice after A-485 administration (Fig. S1b-d). A-485 decreased total fat mass by ~14%, without affecting total lean mass (Fig. 1b, c). These results indicate that A-485-induced weight loss is attributable to decreased fat mass.; Reference: Cell Death Dis. 2020 Sep; 11(9): 745. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486386/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).