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| 25mg |
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Purity: ≥98%
SEL120-34A hydrochloride (SEL-120-34A; SEL12034A) is a novel, potent and selective ATP-competitiveinhibitor of CDK8(Cyclin-dependent kinase 8) with anticancer activity. It binds to the Mediator complex to control transcription. The kinase activities of CDK8/CycC and CDK19/CycC complexes are inhibited by SEL120-34A, with IC50s of 4.4 nM and 10.4 nM, respectively, and a Kdof 3 nM for CDK8. According to X-ray crystallography, SEL120-34A is a type I inhibitor that forms hydrophobic complementarities within the protein's front pocket and halogen bonds with its hinge region. In vitro, SEL120-34A prevents cancer cells' phosphorylation of STAT1 S727 and STAT5 S726. In vivo, the predominant mechanism of action has consistently been observed to be the regulation of STATs- and NUP98-HOXA9-dependent transcription. AML cells with increased STAT5 S726 levels and stem cell features responded differently to treatment with the compound. On the other hand, resistant cells demonstrated lineage commitment and tested negative for activated STAT5. Significant STAT5 S726 repression was correlated with in vivo efficacy in xenotransplanted AML models. Good pharmacokinetics, established safety, and in vivo effectiveness support SEL120-34A'scontinuedclinical development as a tailored treatment strategy for AML.
| Targets |
CDK8/CycC (IC50 = 4.4 nM); CDK19/CycC (IC50 = 10.4 nM); CDK9/cycT (IC50 = 1070 nM)
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| ln Vitro |
SEL120-34A HCl is an ATP-competitive, selective inhibitor of CDK8, with IC50 values of 10.4 nM for CDK19/CycC and 4.4 nM for CDK8/CycC. SEL120-34A HCl only weakly suppresses CDK9 (IC50, 1070 nM) and exhibits no discernible inhibition on CDK1, 2, 4, 6, 5, 7, or 6. According to the effective inhibition range of STAT1 S727 and STAT5 S726, SEL120-34A HCl is active against a panel of AML cell lines (GI50<1 μM), including SKNO-1, KG-1, HEL-60, MOLM-16, MV-4-11, OciAML-2, MOLM-6, and OciAML-3 cells.[1]
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| ln Vivo |
SEL120-34A (30, 60 mg/kg, p.o.) suppresses tumor growth in mice bearing MV4-11 cancer cells. Moreover, oral administration of 30 mg/kg stops the growth of KG-1-derived tumors[1].
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| Cell Assay |
At 2.5 ×105 per well, HCT-116 are seeded onto 6-well plates. The next day, cells are starved of 0.5% FBS for 24 hours to synchronize them, and then they are pretreated for 1 hour with either 0.1% DMSO or SEL120-34A at the indicated concentration. Finally, they are supplemented with 10% FBS, IFNg, or IFNa in the presence of the inhibitor for 4 hours. The cells undergo a 5-minute centrifugation at 1300 rpm in 4°C, a single ice-cold PBS wash, and storage at -80°C.
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| Animal Protocol |
SCID/beige C.B17 female mice xenografted with Colo-205 tumors
5, 15, 30 and 60 mg/kg BID oral |
| References |
| Molecular Formula |
C15H19BR2CLN4
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|---|---|
| Molecular Weight |
450.599160432816
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| Exact Mass |
449.96445
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| Elemental Analysis |
C, 39.98; H, 4.25; Br, 35.47; Cl, 7.87; N, 12.43
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| CAS # |
1609452-30-3
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| Related CAS # |
SEL120-34A monohydrochloride;2443816-41-7;SEL120-34A;1609522-33-9
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| Appearance |
Solid powder
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| SMILES |
CC1=C2C3=C(CCCN3C(=N2)N4CCNCC4)C(=C1Br)Br.Cl
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| InChi Key |
GQXLWUCQESKBSC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H18Br2N4.ClH/c1-9-11(16)12(17)10-3-2-6-21-14(10)13(9)19-15(21)20-7-4-18-5-8-20;/h18H,2-8H2,1H3;1H
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| Chemical Name |
6,7-dibromo-5-methyl-2-piperazin-1-yl-1,3-diazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene;hydrochloride
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| Synonyms |
SEL120-34A monohydrochloride; SEL-120-34A; SEL12034A; SEL120-34A HCl; SEL 120-34A; SEL 12034A; SEL-12034A
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
Water: ~90 mg/mL
Ethanol: ˂1 mg/mL DMSO: 1~62.5 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (Infinity mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: 2.08 mg/mL (Infinity mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2193 mL | 11.0963 mL | 22.1926 mL | |
| 5 mM | 0.4439 mL | 2.2193 mL | 4.4385 mL | |
| 10 mM | 0.2219 mL | 1.1096 mL | 2.2193 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Structure and activity of SEL120-34A.Oncotarget.2017 May 16;8(20):33779-33795. |
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 SEL120-34A inhibits phosphorylation of STAT1 S727 and STAT5 S726 and mitogen induced expression of immediate early response genes.Oncotarget.2017 May 16;8(20):33779-33795. |
 SEL120-34A inhibits interferon- induced genes expression in a dose dependent manner.Oncotarget.2017 May 16;8(20):33779-33795. |
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