Synonym
A-485; A 485; A485.
IUPAC/Chemical 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
InChi Key
VRVJKILQRBSEAG-LFPIHBKWSA-N
InChi Code
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
SMILES Code
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
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
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.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.
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.
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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
97.4 |
181.57 |
| DMF |
10.0 |
18.64 |
| Ethanol |
57.9 |
107.89 |
| Ethanol:PBS (pH 7.2) (1:3) |
0.3 |
0.47 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
536.48
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Waddell A, Mahmud I, Ding H, Huo Z, Liao D. Pharmacological Inhibition of CBP/p300 Blocks Estrogen Receptor Alpha (ERα) Function through Suppressing Enhancer H3K27 Acetylation in Luminal Breast Cancer. Cancers (Basel). 2021 Jun 4;13(11):2799. doi: 10.3390/cancers13112799. PMID: 34199844; PMCID: PMC8200112.
2. Zhang L, Sheng C, Zhou F, Zhu K, Wang S, Liu Q, Yuan M, Xu Z, Liu Y, Lu J, Liu J, Zhou L, Wang X. CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity. Cell Death Dis. 2021 May 12;12(5):476. doi: 10.1038/s41419-021-03761-1. PMID: 33980820; PMCID: PMC8116341.
3. Huo S, Liu X, Zhang S, Lyu Z, Zhang J, Wang Y, Nie B, Yue B. p300/CBP inhibitor A-485 inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss. Int Immunopharmacol. 2021 May;94:107458. doi: 10.1016/j.intimp.2021.107458. Epub 2021 Feb 21. PMID: 33626422.
4. Zhou F, Liu Q, Zhang L, Zhu Q, Wang S, Zhu K, Deng R, Liu Y, Yuan G, Wang X, Zhou L. Selective inhibition of CBP/p300 HAT by A-485 results in suppression of lipogenesis and hepatic gluconeogenesis. Cell Death Dis. 2020 Sep 11;11(9):745. doi: 10.1038/s41419-020-02960-6. PMID: 32917859; PMCID: PMC7486386.
In vitro protocol:
1. Waddell A, Mahmud I, Ding H, Huo Z, Liao D. Pharmacological Inhibition of CBP/p300 Blocks Estrogen Receptor Alpha (ERα) Function through Suppressing Enhancer H3K27 Acetylation in Luminal Breast Cancer. Cancers (Basel). 2021 Jun 4;13(11):2799. doi: 10.3390/cancers13112799. PMID: 34199844; PMCID: PMC8200112.
2. Zhang L, Sheng C, Zhou F, Zhu K, Wang S, Liu Q, Yuan M, Xu Z, Liu Y, Lu J, Liu J, Zhou L, Wang X. CBP/p300 HAT maintains the gene network critical for β cell identity and functional maturity. Cell Death Dis. 2021 May 12;12(5):476. doi: 10.1038/s41419-021-03761-1. PMID: 33980820; PMCID: PMC8116341.
In vivo protocol:
1. Huo S, Liu X, Zhang S, Lyu Z, Zhang J, Wang Y, Nie B, Yue B. p300/CBP inhibitor A-485 inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss. Int Immunopharmacol. 2021 May;94:107458. doi: 10.1016/j.intimp.2021.107458. Epub 2021 Feb 21. PMID: 33626422.
2. Zhou F, Liu Q, Zhang L, Zhu Q, Wang S, Zhu K, Deng R, Liu Y, Yuan G, Wang X, Zhou L. Selective inhibition of CBP/p300 HAT by A-485 results in suppression of lipogenesis and hepatic gluconeogenesis. Cell Death Dis. 2020 Sep 11;11(9):745. doi: 10.1038/s41419-020-02960-6. PMID: 32917859; PMCID: PMC7486386.
1. http://www.thesgc.org/chemical-probes/A-485
2: Lasko LM, Jakob CG, Edalji RP, Qiu W, Montgomery D, Digiammarino EL, Hansen TM, Risi RM, Frey R, Manaves V, Shaw B, Algire M, Hessler P, Lam LT, Uziel T, Faivre E, Ferguson D, Buchanan FG, Martin RL, Torrent M, Chiang GG, Karukurichi K, Langston JW, Weinert BT, Choudhary C, de Vries P, Van Drie JH, McElligott D, Kesicki E, Marmorstein R, Sun C, Cole PA, Rosenberg SH, Michaelides MR, Lai A, Bromberg KD. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017 Oct 5;550(7674):128-132. doi: 10.1038/nature24028. Epub 2017 Sep 27. PubMed PMID: 28953875.
