Description: BI-1347 is a novel, potent and selective CDK8 inhibitor with an IC50 of 1.1 nM. Compound I-003 from patent WO2017202719A1

Physicochemical Properties

Molecular Formula	C22H20N4O
Molecular Weight	356.420404434204
Exact Mass	356.16
Elemental Analysis	C, 74.14; H, 5.66; N, 15.72; O, 4.49
CAS #	2163056-91-3
Related CAS #	2163056-91-3
PubChem CID	132180482
Appearance	Light yellow to yellow solid powder
LogP	3.3
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	503
Defined Atom Stereocenter Count	0
InChi Key	WULUGQONDYDNKY-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H20N4O/c1-25(2)22(27)15-26-14-19(12-24-26)16-7-9-17(10-8-16)21-13-23-11-18-5-3-4-6-20(18)21/h3-14H,15H2,1-2H3
Chemical Name	2-[4-(4-isoquinolin-4-ylphenyl)pyrazol-1-yl]-N,N-dimethylacetamide
Synonyms	BI-1347; BI1347; BI 1347
HS Tariff Code	2934.99.03.00
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	CDK8 (IC50 = 1.1 nM)
ln Vitro	BI-1347 (150 nM; 44 h) increases the production of granzyme B (GZMB+) in mouse splenic NK cells[2]. BI-1347 (0.1 nM-10 μM; 24 h) treatment causes NK92MI cells to secrete more perforin[2].
ln Vivo	BI-1347 (oral gavage; 10 mg/kg; once daily; 30 d) exhibits anti-tumor activity and modulates STAT1S727 phosphorylation in vivo[2]. In the mammary carcinoma EMT6 model, the combination of BI-1347 intermittent schedule and BI-8382 continuous treatment increases efficacy compared to each monotherapy[2].
Cell Assay	Cell Line: Mouse splenic NK cells Concentration: 150 nM Incubation Time: 44 hours Result: Increased the proportion of granzyme B-positive NK cells by approximately 4-fold.
Animal Protocol	B16-F10-luc2 syngeneic melanoma model[2] 10 mg/kg Oral gavage; 10 mg/kg; once daily; 30 d
References	[1]. New phenylpyrazolylacetamide compounds and derivatives as cdk8/cdk19 inhibitors. [2]. Selective and Potent CDK8/19 Inhibitors Enhance NK-Cell Activity and Promote Tumor Surveillance. Mol Cancer Ther. 2020 Apr;19(4):1018-1030.

Solubility Data

Solubility (In Vitro)

DMSO: 71~125 mg/mL (199.2~350.7 mM) Ethanol: ~11 mg/mL (~30.9 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.84 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 (5.84 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 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: ≥ 2.08 mg/mL (5.84 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8057 mL	14.0284 mL	28.0568 mL
	5 mM	0.5611 mL	2.8057 mL	5.6114 mL
	10 mM	0.2806 mL	1.4028 mL	2.8057 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.