ATX inhibitor 5 is a potent orally bioactive autotaxin (ATX) inhibitor (antagonist) with IC50 of 15.3 nM. AATX inhibitor 5 has anti-hepatic fibrosis effects and significantly reduces the level of liver fibrosis induced by CCl4.

Physicochemical Properties

Molecular Formula	C22H18CLF3N6O
Molecular Weight	474.8661
Exact Mass	474.118
CAS #	2402772-45-4
PubChem CID	146014477
Appearance	White to off-white solid powder
LogP	4.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	4
Heavy Atom Count	33
Complexity	688
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C([H])C(=C([H])C=1[H])/C(/[H])=N/N([H])C(N1C([H])([H])C2C(=NC([H])=NC=2C([H])([H])C1([H])[H])N([H])C1=C([H])C([H])=C([H])C(C(F)(F)F)=C1[H])=O
InChi Key	VHRNHTUEITYZIH-VPUKRXIYSA-N
InChi Code	InChI=1S/C22H18ClF3N6O/c23-16-6-4-14(5-7-16)11-29-31-21(33)32-9-8-19-18(12-32)20(28-13-27-19)30-17-3-1-2-15(10-17)22(24,25)26/h1-7,10-11,13H,8-9,12H2,(H,31,33)(H,27,28,30)/b29-11+
Chemical Name	N-[(E)-(4-chlorophenyl)methylideneamino]-4-[3-(trifluoromethyl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxamide
Synonyms	ATX inhibitor 5; ATX inhibitor 5
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

ln Vitro	ATX inhibitor 5 (compound 10g) exhibits action against hepatic stellate cells (HSC) and cardiac fibroblasts (CF) with IC50 values of 1.21 and 0.78 μM [1]. TGF-β-induced collagen content was effectively suppressed by ATX inhibitor 5 at 10 μM [1].
ln Vivo	The CCl4-induced liver fibrosis levels are dramatically decreased by ATX inhibitor 5 (20–40 mg/kg; oral; once daily for two weeks) [1].
Cell Assay	Cell Proliferation Assay[1] Cell Types: CF and t-HSC/Cl-6 Cell Tested Concentrations: 0.0001, 0.01, 1, 100, 10000 µM Incubation Duration: 48 hrs (hours) Experimental Results: Shown for CF and t-HSC/Cl-6 The IC50 for viable cells was 1.21 and 0.78 µM, respectively.
Animal Protocol	Animal/Disease Models: Male Konmin mice (8 weeks old, 22-25 grams) [1] Doses: 20, 40 mg/kg Route of Administration: Oral; one time/day for two weeks Experimental Results: Dramatically diminished CCl4-induced liver damage Fibrosis level.
References	[1]. Optimization and evaluation of novel tetrahydropyrido[4,3-d]pyrimidine derivatives as ATX inhibitors for cardiac and hepatic fibrosis.Eur J Med Chem. 2020 Feb 1;187:111904.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~526.46 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.38 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	2.1058 mL	10.5292 mL	21.0584 mL
	5 mM	0.4212 mL	2.1058 mL	4.2117 mL
	10 mM	0.2106 mL	1.0529 mL	2.1058 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.