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A-485

Catalog No.GC32677

A-485 est un inhibiteur catalytique puissant et sélectif de p300/CBP avec des IC50 de 9,8nM et 2,6nM pour p300 et CBP histone acétyltransférase (HAT), respectivement.

Products are for research use only. Not for human use. We do not sell to patients.

A-485 Chemical Structure

Cas No.: 1889279-16-6

Taille Prix Stock Qté
10mM (in 1mL DMSO)
273,00 $US
En stock
1mg
77,00 $US
En stock
5mg
231,00 $US
En stock
10mg
350,00 $US
En stock
50mg
693,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment:

Cell lines are plated in 96 well or 384 well plates and allowed to adhere for 24 h. The cells are then treated with A-485 for 3, 4, or 5 days. Experiments are run in triplicate and the fraction of viable cells is determined using the Cell Viability Assay according to the manufacturer’s recommendations. For Thymidine incorporation assays, cells are treated with A-485 for 1, 2, 3, or 4 days. Twenty four hours prior to the time point, tritiated thymidine is added and cells are incubated for an additional 24 h. Genomic DNA is then isolated on filter plates[1].

Animal experiment:

The LuCap-77 CR prostate PDX model is used in this study. Donor tumors are dissociated and injected as a brie (1:2) into the right flank of 16 week old male C.B.-17 SCID mice on day 0 in a volume of 0.2 mL. Tumors are size matched on day 26 post-inoculation with a mean tumor volume of 211±3 (SEM) mm3 with dosing beginning on day 28. Mice are randomized into treatment groups using Studylog software based on tumor volume. LuCap-77 CR xenograft tumors are established in SCID mice and animals are dosed with A-485 as for 7 days. Three hours post the final dose, tumors are harvested and snap frozen on dry ice[1].

References:

[1]. Lasko LM, et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017 Oct 5;550(7674):128-132.

Background

A-485 is a potent and selective catalytic inhibitor of p300/CBP with IC50s of 9.8 nM and 2.6 nM for p300 and CBP, respectively.

A three-hour treatment of prostate adenocarcinoma PC-3 cells with A-485 results in a dose-dependent decrease in H3K27Ac, with a half maximal effective concentration (EC50) of 73 nM. Treatment with A-485 does not alter p300 or CBP protein levels. The broadest sensitivity is observed in haematological tumours, where A-485 exhibits potent activity in most multiple myeloma cell lines, and in a subset of acute myeloid leukaemia lines and non-Hodgkin's lymphoma lines. A-485 induces a comparable decrease in H3K27Ac in all five prostate cancer cell lines. Treatment of the androgen-dependent LnCaP-FGC cell line with A-485 attenuates dihydrotestosterone (DHT) stimulated prostate-specific antigen (PSA) expression[1].

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 (PMYC 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].

[1]. Lasko LM, et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours. Nature. 2017 Oct 5;550(7674):128-132.

Chemical Properties

Cas No. 1889279-16-6 SDF
Canonical SMILES O=C(N1CC(N([C@@H](C)C(F)(F)F)CC2=CC=C(F)C=C2)=O)[C@]3(OC1=O)C4=CC=C(NC(NC)=O)C=C4CC3
Formula C25H24F4N4O5 M.Wt 536.48
Solubility DMSO : 100 mg/mL (186.40 mM) Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 1.864 mL 9.32 mL 18.64 mL
5 mM 0.3728 mL 1.864 mL 3.728 mL
10 mM 0.1864 mL 0.932 mL 1.864 mL
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

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Average Rating: 5 ★★★★★ (Based on Reviews and 31 reference(s) in Google Scholar.)

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