 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C15H18BR2N4 |
| Molecular Weight | 414.14 |
| Exact Mass | 449.964 |
| CAS # | 1609522-33-9 |
| Related CAS # | SEL120-34A monohydrochloride;2443816-41-7;SEL120-34A HCl;1609452-30-3 |
| PubChem CID | 73776232 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 22 |
| Complexity | 390 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | GQXLWUCQESKBSC-UHFFFAOYSA-N |
| 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 |
| 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 |
| Synonyms | 1609522-33-9; UNII-6LGR0RYY5Q; SEL120-34A free base; CDK8-IN-2 free base; 6LGR0RYY5Q; 4H-Imidazo(4,5,1-ij)quinoline, 7,8-dibromo-5,6-dihydro-9-methyl-2-(1-piperazinyl)-; 7,8-DIBROMO-5,6-DIHYDRO-9-METHYL-2-(1-PIPERAZINYL)-4H-IMIDAZO(4,5,1-IJ)QUINOLINE; RefChem:182254; |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets |
CDK SEL120-34A is a selective ATP-competitive CDK8 inhibitor with IC50s of 4.4 nM and 10.4 nM for CDK8/CycC and CDK19/CycC, respectively. SEL120-34A has no clear inhibitory impact on CDK1, 2, 4, 6, 5, and 7, and only mildly inhibits CDK9 (IC50, 1070 nM). SEL120-34A is active against a panel of AML cell lines (GI50<1 μM) such as SKNO-1, KG-1, HEL-60, MOLM-16, MV-4-11, OciAML-2, MOLM-6 and OciAML -3 cells, similar with the effective inhibitory range of STAT1 S727 and STAT5 S726 [1]. |
| ln Vitro |
SEL120-34A is a selective ATP-competitive CDK8 inhibitor with IC50s of 4.4 nM and 10.4 nM for CDK8/CycC and CDK19/CycC, respectively. SEL120-34A has no clear inhibitory impact on CDK1, 2, 4, 6, 5, and 7, and only mildly inhibits CDK9 (IC50, 1070 nM). SEL120-34A is active against a panel of AML cell lines (GI50<1 μM) such as SKNO-1, KG-1, HEL-60, MOLM-16, MV-4-11, OciAML-2, MOLM-6 and OciAML -3 cells, similar with the effective inhibitory range of STAT1 S727 and STAT5 S726 [1]. SEL120-34A inhibits STAT1 S727 and STAT5 S726 phosphorylation in a dose-dependent manner in HCT-116 and SET-2 cells upon IFNγ or IFNα stimulation.[1] It suppresses serum-induced expression of immediate early response genes (EGR1 and FOS) in HCT-116 cells.[1] In KG-1 AML cells, SEL120-34A inhibits STAT5 S726 phosphorylation within 1 hour, with sustained inhibition observed after washout, indicating long cellular residence time.[1] Prolonged treatment (up to 6 days) induces apoptosis, evidenced by cleaved Caspase-3.[1] SEL120-34A shows differential growth inhibition in AML cell lines: sensitive lines (KG-1, MV4-11, etc.) have high STAT5 S726/STAT1 S727 phosphorylation; resistant lines (MOLM-13, etc.) are negative for these marks.[1] |
| ln Vivo |
SEL120-34A (30, 60 mg/kg, orally) suppresses tumor growth in mice harboring MV4-11 cancer cells. It also inhibits the growth of tumors produced from KG-1 when administered at a dose of 30 mg/kg [1]. Oral administration of SEL120-34A inhibits tumor growth in KG-1 and MV4-11 AML xenograft models in SCID mice, without significant body weight loss.[1] In Colo-205 CRC xenografts, it reduces phosphorylation of STAT1 S727 and STAT5 S726 in a dose-dependent manner.[1] Transcriptomic analysis of treated tumors shows downregulation of IFN-responsive and STAT-regulated genes (e.g., IRF9, ISG15, STAT1).[1] |
| Enzyme Assay |
Kinase activity of CDK8/CycC and CDK19/CycC was measured using a radiometric protein kinase assay. Dose-response curves were constructed to determine IC₅₀ values at Km ATP concentrations.[1] A Eu kinase binding assay was used to measure binding affinity (Kd) of SEL120-34A to CDK8.[1] Kinase capture experiments using ATP-desthiobiotin probes in KG-1 cell lysates confirmed dose-dependent competitive binding to CDK8.[1] |
| Cell Assay |
Cells were treated with SEL120-34A or vehicle, followed by IFN or serum stimulation. Phosphorylation levels of STAT1 S727, STAT5 S726, and other targets were assessed by Western blot.[1] For gene expression studies, cells were synchronized in low serum, pretreated with compound, stimulated, and RNA was extracted for qRT-PCR.[1] Extended cytotoxicity assays were performed in AML cell lines using AlamarBlue, with GI₅₀ values calculated from dose-response curves over 10 days.[1] |
| Animal Protocol |
SCID mice were inoculated subcutaneously with AML (KG-1, MV4-11) or CRC (Colo-205) cells. Once tumors reached ~100–250 mm³, mice were randomized and treated orally with SEL120-34A dissolved in water, administered once daily or BID.[1] Tumor volumes and body weights were monitored. At endpoints, tumors and blood were collected for pharmacodynamic and pharmacokinetic analyses.[1] A 14-day toxicology study in CD-1 mice involved daily oral dosing, with hematological parameters assessed at study end.[1] |
| ADME/Pharmacokinetics |
Oral administration of 60 mg/kg SEL120-34A in mice resulted in plasma concentrations >700 ng/mL at 16 hours post-dose.[1] The compound showed favorable bioavailability and metabolic stability, enabling in vivo efficacy studies.[1] |
| Toxicity/Toxicokinetics |
In a 14-day subchronic toxicity study in CD-1 mice, SEL120-34A did not cause significant changes in hematological parameters or body weight.[1] |
| References | [1]. SEL120-34A is a novel CDK8 inhibitor active in AML cells with high levels of serine phosphorylation of STAT1 and STAT5 transactivation domains. Oncotarget. 2017 May 16;8(20):33779-33795. |
| Additional Infomation |
CDK8/19 Inhibitor RVU120 is an orally bioavailable inhibitor of cyclin-dependent kinases 8 and 19 (CDK8/19), with potential antineoplastic and chemoprotective activities. Upon oral administration, CDK8/19 inhibitor RVU120 targets, binds to and inhibits the activity of CDK8/19, which prevents activation of CDK8/19-mediated oncogenic signaling pathways, blocks selective transcription of various tumor-promoting genes, and inhibits proliferation of CDK8/19-overexpressing tumor cells. CDK8/19, serine/threonine kinases involved in the regulation of the cell cycle, are overexpressed in certain cancer cell types and play key roles in tumor cell proliferation. SEL120-34A is a tricyclic benzimidazole-based type I CDK8 inhibitor that binds the ATP pocket and forms halogen bonds with the hinge region.[1] It selectively inhibits STAT1/5 serine phosphorylation without affecting tyrosine phosphorylation or CDK9-mediated RNAPII phosphorylation.[1] Transcriptional profiling indicates its effects are enriched in IFN-response and NUP98-HOXA9–regulated genes, suggesting a role in targeting leukemia stem-like cells.[1] It is proposed as a personalized therapeutic candidate for AML with high STAT5 S726 phosphorylation.[1] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4146 mL | 12.0732 mL | 24.1464 mL | |
| 5 mM | 0.4829 mL | 2.4146 mL | 4.8293 mL | |
| 10 mM | 0.2415 mL | 1.2073 mL | 2.4146 mL |