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| Targets |
LysRs-IN-2 targets lysyl-tRNA synthetase (KRS), an essential enzyme that catalyzes the attachment of lysine to its cognate tRNA during protein synthesis. The compound inhibits Plasmodium falciparum KRS (PfKRS) with an IC₅0 of 0.015 microM and Cryptosporidium parvum KRS (CpKRS) with an IC₅0 of 0.13 microM. By inhibiting KRS, the compound blocks protein synthesis in parasites, leading to antiparasitic effects. KRS is a validated target for antiparasitic drug development.
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| 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].
In vitro, LysRs-IN-2 is a potent KRS inhibitor with IC₅0 values of 0.015 microM for PfKRS and 0.13 microM for CpKRS. Its potent inhibitory activity against parasite KRS enzymes makes it a valuable tool for studying KRS biology and for developing antiparasitic therapies. The compound is used in the study of malaria and other parasitic infections. Its selectivity for parasite KRS over human KRS is an important feature for its potential as an antiparasitic agent. |
| 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].
In vivo studies of LysRs-IN-2 are limited, as it is primarily used as a research tool in biochemical and cellular assays. However, given its potent inhibition of parasite KRS, the compound may have potential for in vivo efficacy studies in animal models of malaria and cryptosporidiosis. Further studies are needed to evaluate its pharmacokinetic properties, bioavailability, and efficacy in vivo. The compound's ability to inhibit protein synthesis in parasites suggests it could be developed as an antiparasitic agent. |
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, LysRs-IN-2 is evaluated using aminoacylation assays that measure the attachment of lysine to tRNA by KRS. The compound is incubated with recombinant PfKRS or CpKRS enzyme, lysine, ATP, and tRNA at various concentrations. KRS activity is quantified by measuring the formation of lysyl-tRNA using radiometric or fluorescence-based methods. IC₅0 values are determined from dose-response curves. Selectivity profiling against human KRS may be performed to confirm specificity.
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| Cell Assay |
For in vitro cellular experiments, LysRs-IN-2 is tested in parasite cultures to evaluate its effects on protein synthesis and parasite growth. Plasmodium falciparum or Cryptosporidium parvum are cultured in appropriate media and treated with various concentrations of the compound. Parasite growth is monitored by measuring DNA replication, metabolic activity, or microscopic counting. Protein synthesis is assessed by incorporation of radiolabeled amino acids. The compound's effects on parasite viability are quantified.
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| 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. For in vivo animal experiments, LysRs-IN-2 can be administered to animals via various routes including oral gavage, intravenous injection, or intraperitoneal injection. The compound's efficacy can be evaluated in animal models of malaria or cryptosporidiosis. Typical dosing regimens may range from 1 to 50 mg/kg. Parasite load, survival, and inflammatory markers are assessed. Pharmacodynamic markers such as inhibition of protein synthesis are measured in tissues. Animal studies should follow appropriate ethical guidelines. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of LysRs-IN-2 are not extensively characterized in the literature. As a small molecule with a molecular weight of 355.31, it may have reasonable bioavailability and tissue distribution. The compound's solubility and stability in biological fluids would influence its pharmacokinetic profile. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism and excretion pathways remain to be fully characterized.
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| Toxicity/Toxicokinetics |
Toxicological data for LysRs-IN-2 are limited, as it is primarily a research tool. As a KRS inhibitor that targets protein synthesis, its toxicity would depend on its selectivity for parasite versus human KRS. Inhibition of human KRS could have significant effects on protein synthesis and cell viability. Comprehensive toxicology studies including cytotoxicity screening and selectivity profiling would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
LysRs-IN-2 is a research compound used to study KRS biology and develop antiparasitic therapies. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a KRS inhibitor with IC₅0 values of 0.015 microM for PfKRS and 0.13 microM for CpKRS and is used in the study of malaria and other parasitic infections.
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| Molecular Formula |
C17H16F3NO4
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| Molecular Weight |
355.308455467224
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| Exact Mass |
355.103
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| CAS # |
2170696-76-9
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| PubChem CID |
134158252
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| Appearance |
White to off-white solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
582
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1(CCC(CNC(C2=CC(C3C=C(C=CC=3O2)F)=O)=O)(CC1)O)F
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| InChi Key |
PJBRCGHQNUWERQ-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
N-[(4,4-difluoro-1-hydroxycyclohexyl)methyl]-6-fluoro-4-oxochromene-2-carboxamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ≥ 60 mg/mL (~168.87 mM)
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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