ML167 (also called CID-44968231; NCGC-00188654; ML-167; CID 44968231; NCGC00188654) is a novel, ATP-competitive and highly selective Cdc2-like kinase 4 (Clk4) inhibitor with potential anticancer activity. It exhibits >10-fold selectivity for closely related kinases like Clk1-3 and Dyrk1A/1B, and inhibits Clk4 with an IC50 of 136 nM.

Physicochemical Properties

Molecular Formula	C19H17N3O3
Molecular Weight	335.36
Exact Mass	335.126
Elemental Analysis	C, 68.05; H, 5.11; N, 12.53; O, 14.31
CAS #	1285702-20-6
Related CAS #	1285702-20-6
PubChem CID	44968231
Appearance	Off-white to brown solid powder
Density	1.3±0.1 g/cm3
Boiling Point	531.8±45.0 °C at 760 mmHg
Flash Point	275.4±28.7 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.679
LogP	2.68
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	25
Complexity	438
Defined Atom Stereocenter Count	0
SMILES	OCC1=CC=C(C2=CC3=C(NCC4=CC=C(C)O4)N=CN=C3C=C2)O1
InChi Key	ROCFOIBAEVAOLQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H17N3O3/c1-12-2-4-14(24-12)9-20-19-16-8-13(3-6-17(16)21-11-22-19)18-7-5-15(10-23)25-18/h2-8,11,23H,9-10H2,1H3,(H,20,21,22)
Chemical Name	[5-[4-[(5-methylfuran-2-yl)methylamino]quinazolin-6-yl]furan-2-yl]methanol
Synonyms	CID 44968231; NCGC00188654; ML167; CID44968231; NCGC 00188654; ML-167; CID-44968231; NCGC-00188654; ML 167
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	CLK4 (IC50 = 136 nM); CLK1 (IC50 = 1522 nM); CLK2 (IC50 = 1648 nM); DYRK1B (IC50 = 4420 nM); CDK3 (IC50 ＞10000 nM); DYRK1A (IC50 ＞10000 nM)
ln Vitro	ML167 exhibits cell permeability in Caco-2 cells. A furan ring found in ML167 is susceptible to in vivo metabolism.
ln Vivo
Enzyme Assay	Every compound was screened through the use of the qHTS approach, which generates concentration-response curves for each compound by assaying it at least seven times. The process for establishing a concentration-titration series between subsequent library plate copies in order to conduct large-scale titration-based screening has been explained. In summary, the inter-plate dilution method used in qHTS involves the highest concentration of a set of compounds in DMSO on the first plate, with the same compounds in the same well locations but at successively lower concentrations on subsequent plates. With the help of the above-described protocol, we were able to calculate the plate throughput on the Kalypsys robotic system to be 18 plates/hr, or roughly 7 samples/sec. This implies that a 7 point CRC was obtained on the robotic system once every second.
Animal Protocol
References	[1]. An inhibitor of the Cdc2-like kinase 4 (Clk4).
Additional Infomation	[5-[4-[(5-methyl-2-furanyl)methylamino]-6-quinazolinyl]-2-furanyl]methanol is a member of quinazolines.

Solubility Data

Solubility (In Vitro)

DMSO: ~67 mg/mL (~199.8 mM) Water: <1 mg/mL Ethanol: ~13 mg/mL (~38.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.67 mg/mL (4.98 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 (4.98 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9819 mL	14.9094 mL	29.8187 mL
	5 mM	0.5964 mL	2.9819 mL	5.9637 mL
	10 mM	0.2982 mL	1.4909 mL	2.9819 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.