DYRK1-IN-1 is a selective and ligand-efficient DYRK1A inhibitor. DYRK1-IN-1 inhibits the phosphorylation activity of DYRK1A with IC50 of 220 nM. DYRK1-IN-1 could be utilized as a chemical probe to study CNS penetration of DYRK1A.

Physicochemical Properties

Molecular Formula	C12H12N6
Molecular Weight	240.263880729675
Exact Mass	240.112
CAS #	2814486-79-6
PubChem CID	138454302
Appearance	White to off-white solid powder
LogP	1
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	2
Heavy Atom Count	18
Complexity	284
Defined Atom Stereocenter Count	0
InChi Key	IFLBFWBMAWIBBZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C12H12N6/c1-17(2)12-13-7-5-10(16-12)9-8-15-18-11(9)4-3-6-14-18/h3-8H,1-2H3
Chemical Name	N,N-dimethyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine
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	DYRK1A 220 nM (IC50) DYRK1A 3 nM (Kd) DYRK1B 56 nM (Kd)
ln Vitro	DYRK1-IN-1 has an IC50 value of 220 nM, which inhibits DYRK1A's phosphorylation activity. With an IC50 value of 0.59 μM, DYRK1-IN-1 suppresses the phosphorylation of tau. Without P-glycoprotein liability, DYRK1-IN-1 has good permeability and cellular activity. strong physicochemical characteristics, high levels of enzymatic efficacy, strong aqueous solubility, outstanding kinome selectivity, and a promising inhibitory target in vitro are all displayed by DYRK1-IN-1. A 434 nM IC50 and an enzymatic IC50 of 75 nM demonstrate satisfactory cellular activity in DYRK1-IN-1 (HEK293 cells)[1].
ln Vivo	The clearance of DYRK1-IN-1 (1 mg/kg; intravenous) is high[1].
Animal Protocol	Animal/Disease Models: Sprague−Dawley rats[1] Doses: 1 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Iv Experimental Results: High clearance was observed.
References	[1]. Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors. J Med Chem. 2021;64(15):11709-11728.

Solubility Data

Solubility (In Vitro)

DMSO: 25 mg/mL (104.05 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.41 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 25.0 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	4.1622 mL	20.8108 mL	41.6216 mL
	5 mM	0.8324 mL	4.1622 mL	8.3243 mL
	10 mM	0.4162 mL	2.0811 mL	4.1622 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.