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Purity: ≥98%
QX77 is a novel and potent chaperone-mediated autophagy (CMA) activator. The lysosomal storage disease cystinosis, caused by cystinosin deficiency, is characterized by cell malfunction, tissue failure, and progressive renal injury despite cystine-depletion therapies. Cystinosis is associated with defects in chaperone-mediated autophagy (CMA), but the molecular mechanisms are incompletely understood. Treatment of cystinotic cells with a CMA activator increased LAMP2A localization at the lysosome and increased cell survival. Altogether, we show that LAMP2A trafficking is regulated by cystinosin, Rab11, and RILP and that CMA up-regulation is a potential clinically relevant mechanism to increase cell survival in cystinosis.
ln Vitro |
In Ctns-/- MEFs, QX77 (48 hours) increases the expression levels of Rab11 [1]. Rab11-positive vector vesicles restored the high-motility transport phenotype of wild-type cells, and QX77 restored downregulated LAMP2A expression in Ctns-/-MEFs [1]. In cystine cells, treatment with the CMA activator QX77 prevented Rab11 downregulation and trafficking abnormalities. Additionally, LAMP2A's location on the lysosomal membrane is enhanced by QX77 treatment [1]. QX77 corrects the location of LAMP2A on the lysosomal membrane of cystine cells and dramatically promotes its relocalization to LAMP1-positive lysosomes in cystine cells [1]. QX77 restores the levels of resistance seen in wild-type cells while shielding cystine cells from oxidative damage caused by tert-butyl hydroperoxide. LAMP2A expression is required for QX77 to have an impact on cystine cell survival [1]. In D3 and E14 ES cells, QX77 (10 μM; 0, 3 or 6 days) downregulates pluripotency factors and AP responsiveness, increases LAMP2A expression, activates CMA, and partially loses typical ES cell shape [2].
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Cell Assay |
Western Blot analysis [2]
Cell Types: ES D3 cell line; E14TG2a (E14) Cell line Tested Concentrations: 10 μM Incubation Duration: 3 or 6 days Experimental Results: LAMP2A expression increased, SOX2 and Oct4 protein expression diminished. |
References |
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Molecular Formula |
C16H13CLN2O2
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Molecular Weight |
300.739622831345
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Exact Mass |
300.066
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CAS # |
1798331-92-6
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Related CAS # |
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PubChem CID |
118129505
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Appearance |
Light yellow to yellow solid powder
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LogP |
2.9
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Hydrogen Bond Donor Count |
1
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Hydrogen Bond Acceptor Count |
3
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Rotatable Bond Count |
2
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Heavy Atom Count |
21
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Complexity |
419
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Defined Atom Stereocenter Count |
0
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SMILES |
ClC1C=CC2=C(C=1)OCC(C1C=CC(=CC=1)NC(C)=O)=N2
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InChi Key |
PYCTUCLCTVWILY-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C16H13ClN2O2/c1-10(20)18-13-5-2-11(3-6-13)15-9-21-16-8-12(17)4-7-14(16)19-15/h2-8H,9H2,1H3,(H,18,20)
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Chemical Name |
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (33.25 mM) in 50% PEG300 +50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.3251 mL | 16.6257 mL | 33.2513 mL | |
5 mM | 0.6650 mL | 3.3251 mL | 6.6503 mL | |
10 mM | 0.3325 mL | 1.6626 mL | 3.3251 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.
LAMP2A mislocalization is associated within vivoaccumulation and impaired CMA substrate lysosomal internalization in cystinosis.J BiolChem.2017 Jun 23;292(25):10328-10346. d td> |
CTNS regulates LAMP2A trafficking.J BiolChem.2017 Jun 23;292(25):10328-10346. d td> |
TFEB activation improves lysosomal trafficking and corrects the localization of LAMP2A in cystinotic cells.J BiolChem.2017 Jun 23;292(25):10328-10346. d td> |