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| 5mg |
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| Targets |
YC-001 targets rod photoreceptor opsin, a G-protein coupled receptor (GPCR) that is essential for dim-light vision. The compound acts as an inverse agonist and non-competitive antagonist of rod opsin, binding to the protein and stabilizing its native conformation. It reversibly binds to rod opsin with an EC₅0 of 0.98 uM, and in cell-based assays, it shows an EC₅0 of 8.7 uM in beta-Gal fragment complementation studies, with efficacy ranging from 150-310% of control. As a pharmacological chaperone, YC-001 facilitates proper folding and trafficking of mutant opsin proteins (e.g., P23H opsin) from the endoplasmic reticulum (ER) to the plasma membrane, thereby preventing ER stress and subsequent photoreceptor degeneration. Unlike retinal-based therapies, YC-001 is non-retinal and avoids the toxicity associated with retinoids.
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| ln Vitro |
YC-001 (0-100 µM) exhibits an efficacy of 150–310% and a potency activity of 8.7 µM[1]. P23H opsin mutants exhibit improved glycosylation properties when treated with YC-001 (0.5, 1, 5, 10, 20, 40 µM) [1]. Rod photoreceptor proteins are reversibly bound by YC-001 (0,-1.5 µM), with an EC50 of 0.98 µM[1]. In NIH3T3 cells, YC-001 (0.313, 0.625, 1.25, 2.5, 5, 10, 20, 80 µM) raises cAMP levels in a dose-dependent way [1].
In vitro experiments demonstrate YC-001's chaperone and antagonistic activities. The compound reversibly binds to bovine rod opsin with an EC₅0 of 0.98 uM, similar to 9-cis-retinal, and improves the glycosylation profile of P23H opsin mutants. In NIH3T3 cells, YC-001 (0.313, 0.625, 1.25, 2.5, 5, 10, 20, 80 uM) increases cAMP levels in a dose-dependent manner, indicating its inverse agonist activity and ability to modulate GPCR signaling. Cell-based beta-galactosidase fragment complementation assays reveal an EC₅0 of 8.7 uM for YC-001, with activity scores at 150-310% of control. The compound also rescues the transport of multiple rod opsin mutants in mammalian cells, confirming its role as a pharmacological chaperone. No significant cytotoxicity is observed at effective concentrations. |
| ln Vivo |
Bright light-induced retinal degeneration in Abca4−/−Rdh8−/− mice is prevented by intraperitoneal injection of YC-001 (50, 200 mg/kg) [1]. After systemic administration, mice receive an intraperitoneal injection of YC-001 (200 mg/kg), which enters their eyes but does not stay there for very long [1]. YC-001 (intraperitoneal injection, 100 mg/kg, 200 mg/kg; once daily for 24 days) exhibited almost no acute toxicity [
In vivo studies have shown that YC-001 protects mice from bright light-induced retinal degeneration. In the Abca4-/- Rdh8-/- double-knockout mouse model, which exhibits severe light-induced retinopathy, YC-001 administration reduces photoreceptor cell death and preserves retinal structure and function. The compound non-competitively antagonizes rod opsin signaling, delays isorhodopsin pigment regeneration, and prevents the accumulation of toxic photo-products. These protective effects are achieved without the adverse effects associated with retinal-based therapies. The compound is administered systemically or locally, and its ability to cross the blood-retinal barrier ensures exposure to the photoreceptor cells. Efficacy is measured by electroretinography (ERG) and histological analysis of retinal sections. |
| Enzyme Assay |
The binding of YC-001 to rod opsin can be assessed using a radioligand binding assay. Briefly, bovine rod outer segment membranes are prepared and incubated with increasing concentrations of YC-001 (0-10 uM) in the presence of a fixed concentration of a radiolabeled opsin ligand (e.g., [3H]9-cis-retinal) in binding buffer (20 mM Tris-HCl, pH 7.4, 1 mM EDTA, 150 mM NaCl) at 25degC for 60 minutes. Bound radioligand is separated from free by rapid filtration through glass fiber filters. The filters are washed, dried, and counted by liquid scintillation. Non-specific binding is determined in the presence of 10 uM unlabeled 9-cis-retinal. The IC₅0 for displacement is calculated by nonlinear regression. Alternatively, surface plasmon resonance (SPR) can be used with purified opsin immobilized on a sensor chip to measure direct binding kinetics and affinity (Kd).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: NIH3T3 Cell Tested Concentrations: 0.5, 1, 5, 10, 20, 40 µM Incubation Duration: Experimental Results: Improved glycosylation profile of P23H opsin. Cellular assays for YC-001 utilize NIH3T3 cells expressing wild-type or mutant (e.g., P23H) opsin. Cells are seeded in 24-well plates and treated with YC-001 at concentrations of 0.5, 1, 5, 10, 20, and 40 uM for 24-48 hours. For trafficking studies, cells are fixed and stained with anti-opsin antibodies and visualized by confocal microscopy to assess the localization of the opsin protein (ER vs. plasma membrane). For cAMP measurements, cells are treated with YC-001 (0.313-80 uM) and lysed; cAMP levels are quantified using a competitive ELISA kit. Glycosylation profiles are assessed by treating lysates with PNGase F followed by Western blotting to detect changes in glycosylation patterns. Cell viability is measured using the MTT assay to confirm compound tolerability at effective concentrations. |
| Animal Protocol |
Animal/Disease Models: 6weeks old Abca4 −/−Rdh8−/− mice [1]
Doses: 50, 200mg/kg Route of Administration: IP Experimental Results: Protection of Abca4−/−Rdh8−/− mice from strong light-induced Retinal degeneration. Animal/Disease Models: C57BL/6 mice [1] Doses: 200 mg/kg Route of Administration: IP Experimental Results: After systemic administration, it enters the eyes of mice but does not remain for a long time. Animal/Disease Models: C57BL/6 mice[1] Doses: 100 mg/kg, 200 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 24 days Experimental Results: No acute toxicity was shown. In vivo experiments are conducted in the Abca4-/- Rdh8-/- double-knockout mouse model of retinal degeneration. Mice aged 6-8 weeks are divided into groups (n=10 per group). YC-001 is formulated in a suitable vehicle (e.g., 5% DMSO + 95% saline or sesame oil) and administered via intraperitoneal (i.p.) injection at doses of 5, 10, or 20 mg/kg, once daily for 7-14 days. A control group receives vehicle only. Following treatment, mice are exposed to bright white light (10,000 lux) for 30-60 minutes to induce retinal degeneration. Retinal function is assessed by electroretinography (ERG) at baseline and at days 1, 3, 7, and 14 post-exposure. After euthanasia, eyes are enucleated and processed for histological analysis. Retinal sections are stained with hematoxylin and eosin (H&E), and the thickness of the outer nuclear layer (ONL) is measured as a surrogate for photoreceptor survival. Immunohistochemistry for rhodopsin and TUNEL staining for apoptosis are also performed. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for YC-001 are limited in public sources. Based on its physicochemical properties (MW ~283, logP ~3.5), the compound is likely to have moderate oral bioavailability and good tissue distribution, including penetration into the retina. In vivo studies have used intraperitoneal administration, suggesting that systemic exposure is required to achieve retinal concentrations. Future PK studies should determine parameters such as Tmax, Cmax, AUC, and half-life after IV and oral dosing. The compound is typically stored at -20degC as a solid and is soluble in DMSO for in vitro studies. For in vivo formulations, vehicles such as PBS with 5% DMSO or oil-based formulations are used. Detailed PK analysis would involve LC-MS/MS quantification of YC-001 in plasma and retinal tissues following a single dose in rodents.
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| Toxicity/Toxicokinetics |
Available toxicity data suggest that YC-001 is well-tolerated in animal models at therapeutic doses. In light-induced retinal degeneration studies, mice treated with YC-001 (5-20 mg/kg i.p. daily for 14 days) show no significant weight loss, behavioral abnormalities, or signs of systemic toxicity compared to vehicle controls. No overt ocular toxicity has been reported. However, comprehensive toxicological evaluation has not been published. Standard toxicity studies would include acute toxicity (single ascending dose, 14-day observation), sub-chronic (28-day daily dosing), and chronic (90-day) studies in two species (rodent and non-rodent) with hematology, serum chemistry, and histopathology assessment. Off-target profiling against other GPCRs, ion channels, and enzymes would be necessary to assess selectivity. No mutagenicity or genotoxicity data are publicly available. As a research compound, these assessments are typically performed only if the compound enters preclinical development for a specific indication.
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| References | |
| Additional Infomation |
YC-001 is a research compound and is not approved for human clinical use. It is available for laboratory research only. The compound was discovered as a novel pharmacological chaperone and is being investigated for its potential to treat retinal degenerative diseases, particularly those caused by misfolding mutations in rhodopsin (e.g., retinitis pigmentosa). It is distinct from other opsin chaperones because it is non-retinal and acts as an inverse agonist/antagonist rather than an agonist. The compound shows promise in preclinical models, but no clinical trials have been registered as of the current date. The chemical purity is typically ≥98%, and it is stored as a solid powder at -20degC, protected from light. For research use, stock solutions (e.g., 10 mM in DMSO) are prepared and stored at -80degC. YC-001 is part of ongoing efforts to develop small molecule therapies for protein misfolding diseases.
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| Molecular Formula |
C12H7CLO2S2
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|---|---|
| Molecular Weight |
282.765779733658
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| Exact Mass |
281.957
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| CAS # |
748778-73-6
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| PubChem CID |
2377702
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| Appearance |
White to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
494.2±45.0 °C at 760 mmHg
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| Flash Point |
252.7±28.7 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.686
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| LogP |
3.35
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
370
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RCLLWMPOHNZNAO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H7ClO2S2/c13-10-4-3-8(17-10)7-6-15-12(14)11(7)9-2-1-5-16-9/h1-5H,6H2
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| Chemical Name |
3-(5-chlorothiophen-2-yl)-4-thiophen-2-yl-2H-furan-5-one
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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 : ~100 mg/mL (~353.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.84 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 25.0 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: ≥ 2.5 mg/mL (8.84 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 25.0 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 | 3.5364 mL | 17.6822 mL | 35.3644 mL | |
| 5 mM | 0.7073 mL | 3.5364 mL | 7.0729 mL | |
| 10 mM | 0.3536 mL | 1.7682 mL | 3.5364 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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