LysRs-IN-2 is a lysine tRNA synthetase (KRS) inhibitor (antagonist) with IC50s of 0.015 μM and 0.13 μM against Plasmodium falciparum KRS (PfKRS) and Cryptosporidium parvum KRS (CpKRS), respectively.

Physicochemical Properties

Molecular Formula	C17H16F3NO4
Molecular Weight	355.308455467224
Exact Mass	355.103
CAS #	2170696-76-9
PubChem CID	134158252
Appearance	White to off-white solid powder
LogP	2.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	3
Heavy Atom Count	25
Complexity	582
Defined Atom Stereocenter Count	0
SMILES	FC1(CCC(CNC(C2=CC(C3C=C(C=CC=3O2)F)=O)=O)(CC1)O)F
InChi Key	PJBRCGHQNUWERQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H16F3NO4/c18-10-1-2-13-11(7-10)12(22)8-14(25-13)15(23)21-9-16(24)3-5-17(19,20)6-4-16/h1-2,7-8,24H,3-6,9H2,(H,21,23)
Chemical Name	N-[(4,4-difluoro-1-hydroxycyclohexyl)methyl]-6-fluoro-4-oxochromene-2-carboxamide
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	Plasmodium falciparum 3D7 (EC50=0.27 μM), HsKRS (IC50=1.8 μM), HepG2 cells (EC50=49 μM), and Cryptosporidium parvum (EC50=2.5 μM) in whole-cell bloodstream are all susceptible to LysRs-IN-2's activity [1].
ln Vivo	In a mouse model of P. falciparum SCID, LysRs-IN-2 (1.5 mg/kg; PO once daily for 4 days) reduced parasitemia by 90%. In both INF-gamma knockout mice (a mouse model of Cryptosporidium) and NOD SCID gamma mice, parasite shedding is decreased by LysRs-IN-2 (20 mg/kg; orally once daily for 7 days) [1].
Animal Protocol	Animal/Disease Models: Murine Plasmodium falciparum NODscidIL2Rγnull (SCID) model [1] Doses: 1.5 mg/kg Route of Administration: Orally one time/day for 4 days Experimental Results: 90% reduction in parasitemia in malaria SCID mouse model. Animal/Disease Models: NOD SCID gamma and INF-γ knockout mouse model (Cryptosporidium mouse model) [1] Doses: 20 mg/kg Route of Administration: Orally one time/day for 7 days Experimental Results: Parasite shedding diminished to This reduction was below detectable levels in INF-γ knockout mice and persisted for 3 weeks after treatment was discontinued. In NOD SCID gamma mice, oral administration at a concentration of 20 mg/kg one time/day for 7 days diminished parasite shedding by 96% compared to paromomycin.
References	[1]. Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis. Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7015-7020.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 60 mg/mL (~168.87 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.85 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: ≥ 1.5 mg/mL (4.22 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 15.0 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: ≥ 1.5 mg/mL (4.22 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 15.0 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	2.8144 mL	14.0722 mL	28.1444 mL
	5 mM	0.5629 mL	2.8144 mL	5.6289 mL
	10 mM	0.2814 mL	1.4072 mL	2.8144 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.