SP2509 (Synonyms: HCI-2509, LSD1 Inhibitor VII) |
| رقم الكتالوجGC14631 |
SP2509 هو مضاد فعال وانتقائي لديميثيلاز 1 ليسين محدد (LSD1) مع IC50 من 13 نانومتر
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Cas No.: 1423715-09-6
Sample solution is provided at 25 µL, 10mM.
SP2509 is a novel Lysine specific demethylase 1 (LSD1) antagonist (IC50 = 13nM) with no effect on MAO-A and MAO-B. [1]
LSD1 demethylates mono-/di-methylated lysine 4 on histone H3. High expression of LSD1 is associated with poor prognosis in cancer. [2]
In cultured human AML cells, SP2590 inhibited LSD1 activity, deplete colony growth and elicit apoptosis. SP2590 also inhibited the LSD1 binding to CoREST, increase promoter-specific H3K4Me3 and induces p53, p21 and C/EBPα in AML cells. Moreover, SP2590 promotes differentiated of cultured and primary AML cell. [1]
In mice carrying AML xenografts, SP2590 treatment alone significantly improved the survival of mice and co-treatment with an-HDAC inhibitor (HDI) panobinostat (PS) exhibited superior in vivo activity. [1]
References:
1. Fiskus W, Sharma S, Shah B, Portier BP, Devaraj SG, Liu K, Iyer SP, Bearss D, Bhalla KN. Highly effective combination of LSD1 (KDM1A) antagonist andpan-histone deacetylase inhibitor against human AML cells. Leukemia. 2014 Nov;28(11):2155-64.
2. Zhao ZK, Yu HF, Wang DR, Dong P, Chen L, Wu WG, Ding WJ, Liu YB.
Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients. World J Gastroenterol. 2012 Dec 7;18(45):6651-6.
| Kinase experiment [1]: | |
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SP2509 activity assay |
Test compounds were diluted to 20 × the desired test concentration in 100% dimethyl sulfoxide and 2.5 μl of the diluted drug sample was added to a black 384-well plate. The LSD1 enzyme stock was diluted 17-fold with assay buffer and 40 μl of the diluted LSD1 enzyme was added to the appropriate wells. Substrate, consisting of horseradish peroxidase, dimethyl K4 peptide corresponding to the first 21 amino acids of the N-terminal tail of histone H3, and 10-acetyl-3,7-dihydroxyphenoxazine was then added to wells. Resorufin was analyzed on a plate reader with an excitation wavelength of 530 nm and an emission wavelength of 595 nm. |
| Cell experiment [1]: | |
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Cell lines |
OCI-AML3 and MOLM13 |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
16 h |
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Applications |
SP2509 inhibits LSD1 activity, reduces colony growth and induces apoptosis of cultured AML cells. SP2509 treatment also inhibits the association of LSD1 with CoREST, increases promoter-specific H3K4Me3 and induces p53, p21 and C/EBPα in AML cells. Furthermore, treatment with SP2509 induces differentiation of cultured and primary AML cells |
| Animal experiment [1]: | |
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Animal models |
NOD/SCID mice |
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Dosage form |
25 mg/kg SP2509 administered twice per week (Tuesday and Thursday) intraperitoneally for 3 weeks |
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Applications |
Treatment with either SP2509 improves the median survival of the mice infused with OCI-AML3 cells (37 and 36.5 days, respectively, versus 19.5 days for vehicle control). Notably, combined treatment with panobinostat and SP2509 further improves the median survival of the mice (44.5 days), as compared with treatment with SP2509 or panobinostat alone (P<0.01). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Fiskus W, Sharma S, Shah B et al. Highly effective combination of LSD1 (KDM1A) antagonist andpan-histone deacetylase inhibitor against human AML cells. Leukemia. 2014 Nov;28(11):2155-64 | |
| Cas No. | 1423715-09-6 | SDF | |
| المرادفات | HCI-2509, LSD1 Inhibitor VII | ||
| Chemical Name | (E)-N'-(1-(5-chloro-2-hydroxyphenyl)ethylidene)-3-(morpholinosulfonyl)benzohydrazide | ||
| Canonical SMILES | OC1=CC=C(Cl)C=C1/C(C)=N/NC(C2=CC=CC(S(=O)(N3CCOCC3)=O)=C2)=O | ||
| Formula | C19H20ClN3O5S | M.Wt | 437.9 |
| الذوبان | ≥ 19.45mg/mL in DMSO | Storage | 4°C, protect from light |
| 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 | 2.2836 mL | 11.4181 mL | 22.8363 mL |
| 5 mM | 0.4567 mL | 2.2836 mL | 4.5673 mL |
| 10 mM | 0.2284 mL | 1.1418 mL | 2.2836 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
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
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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