| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
ATP-sensitive potassium channel (KATP) opener (prodrug).
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|---|---|
| ln Vitro |
Foslevcromakalim is a prodrug and is not active in vitro. Its active metabolite, levcromakalim, opens KATP channels, leading to hyperpolarization of smooth muscle cells, vasodilation, and reduction of episcleral venous pressure (EVP).
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| ln Vivo |
In vivo, Foslevcromakalim (QLS-101) reduces intraocular pressure (IOP) in normotensive mice and is suitable for glaucoma research. Upon application into the eye, it is converted to levcromakalim, which dilates blood vessels, lowering both EVP and IOP.
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| Enzyme Assay |
To assess prodrug conversion, alkaline phosphatase is added to a solution containing Foslevcromakalim. The resulting active metabolite, levcromakalim, is then tested in a standard KATP channel binding assay. The assay uses 3H-P1075 as a radioligand and membranes from cells expressing SUR2B/Kir6.1 channels.
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| Cell Assay |
Foslevcromakalim is tested in cultured human trabecular meshwork (HTM) cells or Schlemms canal endothelial cells to assess its conversion to levcromakalim. The active metabolite's ability to increase intracellular cGMP levels or nitric oxide production can be measured.
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| Animal Protocol |
In vivo studies are conducted in normotensive or glaucomatous animal models, such as mice or rabbits. IOP is measured using a tonometer at baseline and after topical ocular administration of Foslevcromakalim. The compound is typically formulated as an ophthalmic solution.
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| ADME/Pharmacokinetics |
Upon application into the eye, Foslevcromakalim is converted to levcromakalim by alkaline phosphatase, which then exerts its ocular hypotensive effect. Its half-life and systemic absorption are likely low due to its local administration.
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| Toxicity/Toxicokinetics |
Preclinical safety data specific to Foslevcromakalim is limited. However, as a KATP opener, it may cause systemic vasodilation and hypotension if absorbed. It has been granted Orphan Drug Designation, indicating a favorable safety profile for its intended use.
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| References |
[1]. Pervan-Steel CL, et al. Ocular Hypotensive Properties and Biochemical Profile of QLS-101, a Novel ATP-Sensitive Potassium (KATP) Channel Opening Prodrug. Invest Ophthalmol Vis Sci. 2022 Apr 1;63(4):26.
[2]. WHO Drug Information-World Health Organization (WHO). |
| Additional Infomation |
Forslecrocaline is an ophthalmic solution containing the prodrug of levoclocaline, an ATP-sensitive potassium channel (KATP channel) modulator with potential vasodilatory and episcleral venous pressure (EVP)-lowering effects. Upon instillation into the eye, Forslecrocaline is converted to levoclocaline, which dilates blood vessels by opening KATP channels, thereby reducing episcleral venous pressure and elevated intraocular pressure (IOP).
Foslevcromakalim (QLS-101) is an investigational ophthalmic solution for the treatment of glaucoma and ocular hypertension. It has been granted Orphan Drug Designation by the FDA. It is a prodrug of the potent KATP channel opener, levcromakalim. |
| Molecular Formula |
C16H19N2O6P
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|---|---|
| Molecular Weight |
366.305625200272
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| Exact Mass |
366.098
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| CAS # |
1802655-72-6
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| PubChem CID |
91826794
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
-0.3
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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 |
638
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1([C@H]([C@@H](C2=C(O1)C=CC(=C2)C#N)N3CCCC3=O)OP(=O)(O)O)C
|
| InChi Key |
JRUHOGHWZXTUMZ-CABCVRRESA-N
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| InChi Code |
InChI=1S/C16H19N2O6P/c1-16(2)15(24-25(20,21)22)14(18-7-3-4-13(18)19)11-8-10(9-17)5-6-12(11)23-16/h5-6,8,14-15H,3-4,7H2,1-2H3,(H2,20,21,22)/t14-,15+/m1/s1
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| Chemical Name |
[(3S,4R)-6-cyano-2,2-dimethyl-4-(2-oxopyrrolidin-1-yl)-3,4-dihydrochromen-3-yl] dihydrogen phosphate
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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: 60 mg/mL (163.80 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (8.19 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 30.0 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: ≥ 3 mg/mL (8.19 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 30.0 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: ≥ 3 mg/mL (8.19 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 | 2.7299 mL | 13.6496 mL | 27.2993 mL | |
| 5 mM | 0.5460 mL | 2.7299 mL | 5.4599 mL | |
| 10 mM | 0.2730 mL | 1.3650 mL | 2.7299 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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