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| Targets |
Apolipoprotein LI (APOL1)[1]
The primary target of APOL1-IN-1 is apolipoprotein L1 (APOL1), a pore-forming protein that is part of the high-density lipoprotein complex. APOL1 has two common risk variants (G1 and G2) that are associated with increased risk of FSGS and CKD in individuals of African descent. By inhibiting APOL1, the compound may prevent the pore-forming activity that leads to podocyte injury and kidney disease. |
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| ln Vitro |
In vitro studies demonstrate that APOL1-IN-1 is a potent inhibitor of APOL1. The compound's activity has been characterized in biochemical and cell-based assays. As an inhibitor of a pore-forming protein, it likely blocks the membrane-disrupting activity of APOL1, preventing the cytotoxicity associated with APOL1 risk variants. These studies support the compound's potential for treating APOL1-mediated kidney diseases.
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| ln Vivo |
In vivo activity data for APOL1-IN-1 are limited, as the compound is a research tool for studying APOL1 biology. The compound may be tested in animal models of APOL1-mediated kidney disease to assess its efficacy in preventing or treating kidney injury. However, specific in vivo studies have not been extensively reported in the available literature.
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| Enzyme Assay |
Non-cellular assays for APOL1-IN-1 typically involve measuring its binding affinity to APOL1 or its ability to inhibit APOL1 pore-forming activity. The compound is incubated with purified APOL1 protein, and binding is assessed using surface plasmon resonance or isothermal titration calorimetry. Pore-forming activity can be measured using liposome leakage assays or planar lipid bilayer electrophysiology.
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| Cell Assay |
In vitro cellular assays for APOL1-IN-1 are conducted using cell lines expressing APOL1 risk variants. Cells are treated with the compound, and APOL1-mediated cytotoxicity is assessed by measuring cell viability, membrane permeability, or apoptotic markers. These assays demonstrate the compound's ability to protect cells from APOL1-induced injury. Cell-based assays may also assess the effects on APOL1 expression and localization.
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| Animal Protocol |
In vivo animal experiments for APOL1-IN-1 may use transgenic mouse models expressing human APOL1 risk variants. The compound is administered orally or intravenously, and kidney function is assessed by measuring proteinuria, serum creatinine, and blood urea nitrogen. Kidney histology is examined for evidence of glomerulosclerosis and podocyte injury. These studies evaluate the compound's potential for treating APOL1-mediated kidney diseases.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of APOL1-IN-1 are not well-characterized. The compound has a molecular weight of 381.40 g/mol. Its solubility, stability, and bioavailability have not been extensively reported. As a research compound, its pharmacokinetic profile would depend on its formulation and route of administration. Further studies are needed to characterize its ADME properties.
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| Toxicity/Toxicokinetics |
Toxicological data for APOL1-IN-1 are limited, as it is a research reagent not intended for human use. Standard laboratory safety precautions should be followed when handling the compound. No significant toxicity has been reported in the available literature. The compound is for research use only and should not be administered to humans.
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| References |
[1]. Brodney M, et, al. Inhibitors of apol1 and methods of using same. WO2020131807A1.
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| Additional Infomation |
Other information includes APOL1-IN-1's role as a potent inhibitor of apolipoprotein L1 (APOL1). It can be used to study the pathogenesis of focal segmental glomerulosclerosis (FSGS) and non-diabetic kidney disease (NDKD). The compound is derived from patent WO2020131807A1 as compound 87. It is available as a research reagent for kidney disease research.
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| Molecular Formula |
C21H20FN3O3
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|---|---|
| Molecular Weight |
381.40
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| Exact Mass |
381.148
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| CAS # |
2446817-72-5
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| PubChem CID |
147257822
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| Appearance |
White to off-white solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
581
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1[C@H]([C@@H](C(=O)N1)NC(=O)CCC2=C(NC3=CC=CC=C32)C4=CC=C(C=C4)F)O
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| InChi Key |
CNYZYDUBGMRAFP-XLIONFOSSA-N
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| InChi Code |
InChI=1S/C21H20FN3O3/c22-13-7-5-12(6-8-13)19-15(14-3-1-2-4-16(14)24-19)9-10-18(27)25-20-17(26)11-23-21(20)28/h1-8,17,20,24,26H,9-11H2,(H,23,28)(H,25,27)/t17-,20+/m1/s1
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| Chemical Name |
3-[2-(4-fluorophenyl)-1H-indol-3-yl]-N-[(3S,4R)-4-hydroxy-2-oxopyrrolidin-3-yl]propanamide
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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 |
| 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: 125 mg/mL (327.74 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6219 mL | 13.1096 mL | 26.2192 mL | |
| 5 mM | 0.5244 mL | 2.6219 mL | 5.2438 mL | |
| 10 mM | 0.2622 mL | 1.3110 mL | 2.6219 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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