ACY-957 |
Catalog No.GC30526
One-Click Copy Product Info
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ACY-957 es un inhibidor selectivo y activo por vÍa oral de HDAC1 y HDAC2, con IC50 de 7 nM, 18 nM y 1300 nM contra HDAC1/2/3, respectivamente, y no muestra inhibiciÓn sobre HDAC4/5/6/7/8 /9.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1609389-52-7
Sample solution is provided at 25 µL, 10mM.
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ACY-957 is an orally active and selective chemical inhibitor of HDAC1 and HDAC2 with IC50 values of 7nM and 18nM, respectively [1]. ACY-957 inhibits the expression levels of HbG mRNA and HbF protein and suppressed Bcl11A and Sox6 mRNA levels through the induction of Gata2 [2]. ACY-957 has been widely used to regulate the numbers of red blood cells, platelets and total cells in the bone marrow of Mx-Cre mouse models[3].
In vitro, ACY-957 treatment for 72h significantly inhibited the cell viability of MV-4-11, Kasumi-1 and HL-60 cells, with IC50 values of 0.8μM, 1.6μM and 2.2μM, respectively[4]. Treatment with 2μM ACY-957 for 72 hours significantly induced cell cycle arrest and apoptosis in SUDHL4 cells, and led to a significant increase in H3K27ac levels[5].
In vivo, ACY-957 treatment via oral administration at a dose of 75mg/kg, five times a week for 3 weeks, significantly increased HBG mRNA expression in the blood of non-anemic cynomolgus monkeys and led to the accumulation of HbG protein[6]. Oral administration of ACY-957 at a dose of 30mg/kg daily for 6 days led to elevated HbE expression in the blood of rats and a slight decrease in body weight[7].
References:
[1] Shearstone J R, Golonzhka O, Chonkar A, et al. Chemical inhibition of histone deacetylases 1 and 2 induces fetal hemoglobin through activation of GATA2[J]. PloS one, 2016, 11(4): e0153767.
[2] Shearstone J R, van Duzer J H, Jones S S, et al. Mechanistic insights into fetal hemoglobin (HbF) induction through chemical inhibition of histone deacetylase 1 and 2 (HDAC1/2)[J]. Blood, 2013, 122(21): 2253.
[3] Shearstone J R, van Duzer J H, Jones S S, et al. Pharmacological Inhibition Of Histone Deacetylase (HDAC) 1, 2 Or 3 Have Distinct Effects On Cellular Viability, Erythroid Differentiation, and Fetal Globin (HbG) Induction[J]. Blood, 2013, 122(21): 564.
[4] Min C, Moore N, Shearstone J R, et al. Selective inhibitors of histone deacetylases 1 and 2 synergize with azacitidine in acute myeloid leukemia[J]. PloS one, 2017, 12(1): e0169128.
[5] Johnson D P, Spitz G S, Tharkar S, et al. HDAC1, 2 inhibition impairs EZH2-and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma[J]. Oncotarget, 2014, 6(7): 4863.
[6] Chonkar A, Jarpe M, Bhol K, et al. The histone deacetylase 1 and 2 (HDAC1/2) inhibitor ACY-957: impact of dosing schedule on pharmacokinetics (PK), pharmacodynamics (PD), hematopoietic toxicity, and gamma globin (HBG, γ) expression in monkey[J]. Blood, 2016, 128(22): 323.
[7] Shearstone J R, Chonkar A, Bhol K, et al. The histone deacetylase 1 and 2 (HDAC1/2) Inhibitor ACY-957 Increases Epsilon (HbE) and Gamma (HbG) Globin mRNA in the peripheral blood of non-anemic rats and monkeys[J]. Blood, 2015, 126(23): 3378.
| Cell experiment [1]: | |
Cell lines | Karpas-422 cells |
Preparation Method | Karpas-422 cells were grown in RPMI 1640 medium supplemented with, 1% penicillin/streptomycin, and 10% heat-inactivated fetal bovine serum (FBS) in 384-well plates at a density of 2.5×105 cells/ml at 37°C in an incubator with 5% CO2. Different concentrations of ACY-957 (2μM) were added and incubated at 37°C with 5% CO2 for 48h. Cell viability was measured. |
Reaction Conditions | 2μM; 48h |
Applications | ACY-957 treatment significantly reduced cell viability of Karpas-422 cells. |
| Animal experiment [2]: | |
Animal models | Female Crl:NU(NCr)-Foxn1nu mice |
Preparation Method | Female Crl:NU(NCr)-Foxn1nu mice were injected subcutaneously with 1×107 MOLM-13 cells in 50% Matrigel in the right flank. When tumors reached an average size of 100-150mm3, mice (n=10/group) were randomized into 3 treatment groups: Azacitidine, ACY-957, and vehicle control. Azacitidine was administered intravenously (i.v.) twice weekly at 5.5mg/kg in saline while ACY-957 was administered orally (p.o.) daily at 125mg/kg in 0.5% hydroxypropyl methylcellulose in deionized water. Mice were treated for 28 days. Tumors were measured twice weekly in two dimensions using calipers and volume was calculated by width2×length/2. |
Dosage form | 125mg/kg/day for 28 days; p.o. |
Applications | ACY-957 treatment significantly inhibited tumor growth in the MOLM-13 xenograft mouse model. |
References: | |
| Cas No. | 1609389-52-7 | SDF | |
| Canonical SMILES | O=C(C1=CC=C2N=C(N3CCNCC3)C=CC2=C1)NC4=CC(C5=CC=CS5)=CC=C4N | ||
| Formula | C24H23N5OS | M.Wt | 429.54 |
| Solubility | DMSO : 83.33 mg/mL (194.00 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3281 mL | 11.6404 mL | 23.2807 mL |
| 5 mM | 465.6 μL | 2.3281 mL | 4.6561 mL |
| 10 mM | 232.8 μL | 1.164 mL | 2.3281 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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 saline, 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.
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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% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 2 reference(s) in Google Scholar.)