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QX77

Alias: QX-77;QX 77;QX77
Cat No.:V4038 Purity: ≥98%
QX77 is a novel and potent chaperone-mediated autophagy (CMA) activator.
QX77
QX77 Chemical Structure CAS No.: 1798331-92-6
Product category: Autophagy
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
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].
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

[1]. Cystinosin, the small GTPase Rab11, and the Rab7 effector RILP regulate intracellular trafficking of the chaperone-mediated autophagy receptor LAMP2A. J Biol Chem. 2017 Jun 23;292(25):10328-10346.

[2]. Chaperone-mediated autophagy regulates the pluripotency of embryonic stem cells. Science. 2020 Jul 24;369(6502):397-403.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C16H13CLN2O2
Molecular Weight
300.739622831345
Exact Mass
300.066
CAS #
1798331-92-6
Related CAS #
1798331-92-6
PubChem CID
118129505
Appearance
Light yellow to yellow solid powder
LogP
2.9
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
2
Heavy Atom Count
21
Complexity
419
Defined Atom Stereocenter Count
0
SMILES
ClC1C=CC2=C(C=1)OCC(C1C=CC(=CC=1)NC(C)=O)=N2
InChi Key
PYCTUCLCTVWILY-UHFFFAOYSA-N
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)
Chemical Name
N-(4-(7-Chloro-2H-benzo[b][1,4]oxazin-3-yl)phenyl)acetamide
Synonyms
QX-77;QX 77;QX77
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO:≥ 60mg/mL
Water:N/A
Ethanol:N/A
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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • QX77

    LAMP2A mislocalization is associated within vivoaccumulation and impaired CMA substrate lysosomal internalization in cystinosis.2017 Jun 23;292(25):10328-10346. d

  • QX77

    CTNS regulates LAMP2A trafficking.2017 Jun 23;292(25):10328-10346. d

  • QX77

    TFEB activation improves lysosomal trafficking and corrects the localization of LAMP2A in cystinotic cells.2017 Jun 23;292(25):10328-10346. d

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