A-485 |
| رقم الكتالوجGC32677 |
A-485 هو مثبط حفزي قوي وانتقائي لـ p300 / CBP مع IC50s من 9.8 نانومتر و 2.6 نانومتر لـ p300 و CBP هيستون أسيتيل ترانسفيراز (HAT) ، على التوالي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1889279-16-6
Sample solution is provided at 25 µL, 10mM.
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A-485 is a potent and selective p300/CBP (histone acetyltransferase paralog/CREB binding protein) catalytic inhibitor with IC50 of 60nM for p300 HAT. A-485 inhibits the activity of p300-BHC (bromodomain HAT-C/H3) and CBP-BHC domains with IC50 of 9.8nM and 2.6nM, respectively. A-485 selectively inhibits the proliferation of lineage-specific tumor types, including several hematological malignancies and androgen receptor-positive prostate cancer [1-2].
A-485 reduces the level of acetylated histone H3 lysine 27 (H3K27Ac) in PC3 cells in a concentration-dependent manner with an EC50 of 73nM, but has little effect on H3K9Ac (EC50 > 10mM) [1]. A-485 has an inhibitory effect on H3K27Ac in three melanoma cell lines (WM2664, SKMEL5 and A375 cells) with IC50 of 0.59, 0.93 and 0.96μM, respectively. A-485 significantly induces cell senescence in sensitive melanoma cell lines WM2664 and SKMEL5, but no similar effect was observed in resistant A375 cells [3].
A-485 reduced tumor volume (54%) in the LuCaP-77 CR mouse xenograft model of castration-resistant prostate cancer when administered at a dose of 100mg/kg for 21 days [1]. In the GH3 cell xenograft nude mouse model, A-485 can significantly inhibit tumor volume (50mg/kg group inhibited 32.37%, 100mg/kg group inhibited 54.15%) and tumor weight (50mg/kg group inhibited 43.83% , the 100mg/kg group inhibited 61.41%) [4].
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.
[2] Tottone L, Zhdanovskaya N, Carmona Pestaña Á, Zampieri M, Simeoni F, Lazzari S, Ruocco V, Pelullo M, Caiafa P, Felli MP, Checquolo S, Bellavia D, Talora C, Screpanti I, Palermo R. Histone Modifications Drive Aberrant Notch3 Expression/Activity and Growth in T-ALL. Front Oncol. 2019 Apr 3;9:198.
[3] Wang R, He Y, Robinson V, Yang Z, Hessler P, Lasko LM, Lu X, Bhathena A, Lai A, Uziel T, Lam LT. Targeting Lineage-specific MITF Pathway in Human Melanoma Cell Lines by A-485, the Selective Small-molecule Inhibitor of p300/CBP. Mol Cancer Ther. 2018 Dec;17(12):2543-2550.
[4] Ji C, Xu W, Ding H, et al. The p300 inhibitor A-485 exerts antitumor activity in growth hormone pituitary adenoma[J]. The Journal of Clinical Endocrinology & Metabolism, 2022, 107(6): e2291-e2300.
| Cell experiment [1]: | |
Cell lines | Human T-ALL cell lines |
Preparation Method | TALL-1 cell lines were treated with 5μM A-485 or an equal volume of vehicle (DMSO), and 48 hours later, live TALL-1 cells were transiently transfected with an expression vector encoding human c-Myc. Cell viability was measured by MTS assay. |
Reaction Conditions | 5μM, 48h |
Applications | A-485 inhibited the viability of TALL-1 cells, and the expression of exogenous c-Myc partially saved the viability of NotCH3-dependent TALL-1 cells exposed to A-485. |
| Animal experiment [2]: | |
Animal models | LuCaP-77 CR xenograft model |
Preparation Method | LuCap-77 CR xenograft tumors were established in SCID mice, and A-485 was administered intraperitoneally (ip) at a dose of 100mg/kg twice daily for 21 days. |
Dosage form | 100mg/kg, twice daily for 21 days , i.p. |
Applications | After 21 days of administration, A-485 inhibited tumor growth by 54% compared to vehicle control. |
References: | |
| 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 |
| الذوبان | 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. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
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.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)
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