SEL120-34A mono HCl is a selective, ATP-competitive CDK8 inhibitor (antagonist) with IC50s of 4.4 nM and 10.4 nM for CDK8/CycC and CDK19/CycC complexes, respectively, and a Kd of 3 nM for CDK8. SEL120-34A mono HCl has a very weak effect on CDK9, with a calculated IC50 of 1070 nM, but has no effect on CDK1, 2, 4, 6, 5, 7, etc. SEL120-34A mono HCl inhibits the phosphorylation of STAT1 S727 and STAT5 S726. Has anti-tumor activity.

Physicochemical Properties

Molecular Formula	C15H19BR2CLN4
Molecular Weight	450.599160432816
Exact Mass	449.964
CAS #	2443816-41-7
Related CAS #	SEL120-34A HCl;1609452-30-3;SEL120-34A;1609522-33-9
PubChem CID	73776232
Appearance	White to off-white solid powder
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
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	CDK8/CycC 4.4 nM (IC50) CDK19/CycC 10.4 nM (IC50) CDK9/cycT 1070 nM (IC50)
ln Vitro	SEL120-34A monohydrochloride is an ATP-competitive, selective CDK8 inhibitor that inhibits the kinase activities of CDK8/CycC and CDK19/CycC complexes. Its Kd for CDK8 is 3 nM, and its IC50s are 4.4 nM and 10.4 nM, respectively. Although SEL120-34A monohydrochloride has no discernible activity against CDK1, 2, 4, 6, 5, 7, it slightly inhibits CDK9 (IC50=1070 nM)[1]. SEL120-34A (1.6 nM-5 μM) is not harmful to S726 negative MOLM13 AML cells, however it suppresses the development of STAT5 S726 positive KG-1 AML cells[1]. The phosphorylation of STAT1 S727 and STAT5 S726 is inhibited by SEL120-34A monohydrochloride, which also reduces the expression of IRF9 and STAT1 mRNA and mitogen-induced IER[1].
ln Vivo	SEL120-34A monohydrochloride (30, 60 mg/kg, po once a day) suppresses growth of AML tumors in a dose-dependent manner in SCID mice after treatment for 17 days[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.

Solubility Data

Solubility (In Vitro)

H2O : 50 mg/mL (110.96 mM) DMSO : 16.67 mg/mL (37.00 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (3.71 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 16.7 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: ≥ 1.67 mg/mL (3.71 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 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 1.67 mg/mL (3.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 14.29 mg/mL (31.71 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).  (Please use freshly prepared in vivo formulations for optimal results.)

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.