PAT-1251 is a potent, selective, orally bioavailable lysyl oxidase-like protein 2 (LOXL2) inhibitor (antagonist) with IC50s of 0.71 and 1.17 μM for hLOXL2 and hLOXL3, respectively. It is also effective against mice and rats. The inhibitory activity of mouse and dog LOXL2 is very strong, with IC50s of 0.10, 0.12 and 0.16 μM respectively; PAT-1251 may be utilized in study/research of a variety of fibrotic diseases.

Physicochemical Properties

Molecular Formula	C18H17F4N3O3
Molecular Weight	399.339498281479
Exact Mass	399.12
CAS #	2007885-39-2
Related CAS #	Lenumlostat hydrochloride;2098884-53-6
PubChem CID	122536283
Appearance	Light yellow to yellow solid powder
LogP	1.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	551
Defined Atom Stereocenter Count	2
SMILES	F[C@@H]1CN(C(C2C=CC=C(C=2)OC2C=C(CN)C=C(C(F)(F)F)N=2)=O)C[C@H]1O
InChi Key	ODGXXYXJORZPHE-ZIAGYGMSSA-N
InChi Code	InChI=1S/C18H17F4N3O3/c19-13-8-25(9-14(13)26)17(27)11-2-1-3-12(6-11)28-16-5-10(7-23)4-15(24-16)18(20,21)22/h1-6,13-14,26H,7-9,23H2/t13-,14-/m1/s1
Chemical Name	[3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxyphenyl]-[(3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl]methanone
Synonyms	PAT1251; PAT 1251; PAT-1251
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 (e.g. under nitrogen), 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

ln Vitro	PAT-1251 is a lysyl oxidase-like 2 (LOXL2) inhibitor that potently inhibits LOXL2 in mice, rats, and dogs (IC50 of 0.10, 1.17 μM, respectively), and has IC50 values of 0.71 and 1.17 μM for hLOXL2 and hLOXL3, respectively. 0.12 and 0.16 μM), in that order. With an inhibition rate of less than 10% at 10 μM, PAT-1251 exhibits selectivity for LOXL2 over other important members of the amine oxidase family, including diamine oxidase (DAO), copper-dependent amine oxidase, semicarbazide-sensitive amine oxidase (SSAO), and flavin-dependent Monoamine oxidase A (MAO-A) and B (MAO-B) [1].
References	[1]. Identification of 4-(Aminomethyl)-6-(trifluoromethyl)-2-(phenoxy)pyridine Derivatives as Potent, Selective, and Orally Efficacious Inhibitors of the Copper-Dependent Amine Oxidase, Lysyl Oxidase-Like 2 (LOXL2). J Med Chem. 2017 May 25;60(10):4403-4423.
Additional Infomation	PAT-1251 is under investigation in clinical trial NCT04054245 (PAT-1251 in Treating Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocytosis Myelofibrosis). Lenumlostat is an orally available, small-molecule, irreversible inhibitor of lysyl oxidase homolog 2 (lysyl oxidase-like protein 2; LOXL2) with potential antifibrotic activity. Upon oral administration, the aminomethyl pyridine moiety of lenumlostat interacts with the active site of LOXL2 to form a pseudo-irreversible inhibitory complex, thereby inhibiting the catalytic activity of LOXL2. LOXL2, a secreted glycoprotein, catalyzes the post-translational oxidative deamination of lysine residues on target proteins, including collagen and elastin, leading to the formation of deaminated lysine (allysine). Condensation with other allysines or lysines drives the formation of inter- and intramolecular cross-linkages that impact remodeling of the extracellular matrix (ECM), potentially leading to fibrosis. Inhibition of LOXL2, which is often upregulated in fibrotic tissue, may reduce fibrosis in certain chronic fibrotic diseases.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 130 mg/mL (~325.54 mM) H2O : ≥ 100 mg/mL (~250.41 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.17 mg/mL (5.43 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 21.7 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: ≥ 2.17 mg/mL (5.43 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 21.7 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: ≥ 2.17 mg/mL (5.43 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 21.7 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	2.5041 mL	12.5207 mL	25.0413 mL
	5 mM	0.5008 mL	2.5041 mL	5.0083 mL
	10 mM	0.2504 mL	1.2521 mL	2.5041 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.