(R)-SM875
(R)-SM875 is a cellular prion protein (PrP) degrader with an IC50 of 3 μM in HEK293 cells. (R)-SM875 interacts with PrP folding intermediates, binds to a binding pocket unique to FI-PrP, inhibits PrPC maturation, blocks prion replication, and induces cytotoxicity, autophagy, PrPC aggregation, as well as lysosome-dependent autophagy-mediated post-translational degradation of PrPC, without altering the mRNA level of PrPC. (R)-SM875 can be used in research related to prion diseases.
For research use only. We do not sell to patients.
- CAS No.: 2715974-36-8
- Formula: C19H16BrN3O3
- Molecular Weight:414.25
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
|
PrP 3 μM (IC50) |
In Vitro
(R)-SM875 interacts with the ADMPC chiral stationary phase model with a more favorable Gibbs free energy (-7.5 kcal/mol) and a broader range of binding interactions compared to its (S)-enantiomer[1].
(R)-SM875 (0.1-30 μM; 48 h) potently reduces cellular prion protein levels in HEK293 cells with an IC50 of 3 μM[1].
(R)-SM875 (0.1-30 μM; 48 h) exhibits cytotoxicity in HEK293 cells within its active concentration range, with an LD50 above 30 μM in ZR-75-1 cells and above 10 μM in RK-13 cells[1].
(R)-SM875 (500 ns) forms dynamic, stable interactions with the prion protein folding intermediate over a 500 ns molecular dynamics simulation, including π-π stacking, π-cation, and hydrogen bond interactions with key PrP residues[1].
(R)-SM875 dose-dependently lowers mouse PrPC levels in stably transfected HEK293 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
-
Cell Line:HEK293 cells
-
Concentration:0.1-30 μM
-
Incubation Time:48 h
-
Result:Reduced cellular prion protein levels in a dose-dependent manner, with an IC50 of 3 μM.
-
Cell Line:HEK293, ZR-75-1, and RK-13 cells
-
Concentration:0.1-30 μM
-
Incubation Time:48 h
-
Result:Caused cytotoxicity in HEK293 cells within its active concentration range.
Showed an LD50 higher than 30 μM in ZR-75-1 cells.
Showed an LD50 higher than 10 μM in RK-13 cells.
Chemical Information
-
CAS No. 2715974-36-8
-
Molecular Weight 414.25
-
Formula C19H16BrN3O3
-
SMILES
O=C1NC2=C(C=NN2C3=CC=C(C=C3)Br)[C@@H](C4=CC(OC)=C(C=C4)O)C1
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
-
Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
-
Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
-
Autophagy
Autophagy is a process in which eukaryotic cells use lysosomes to degrade their own cytoplasmic proteins and damaged organelles under the regulation of autophagy related gene (Atg). Microtubule-associated proteins light chain 3 (LC3) is recognized as autophagy marker, which transfers from cytoplasmic LC3 (LC3-I) to membrane type (LC3-II). LC3-II/I ratio could be detected by Western Blot and fluorescence microscopy.
-
Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
-
Macroautophagy Solutions
Macroautophagy is a conserved lysosome-dependent degradation pathway in which cytoplasmic material is sequestered into double-membrane autophagosomes and delivered to lysosomes for degradation and recycling. The pathway supports cellular homeostasis during nutrient limitation, organelle stress, protein-aggregate accumulation, infection, differentiation, and tissue remodeling by coupling cargo sequestration, autophagosome maturation, lysosomal fusion, and degradation of cargo-derived macromolecules. The core molecular sequence includes initiation by nutrient- and stress-regulated autophagy machinery, autophagosome nucleation, LC3/ATG8-family conjugation to autophagosomal membranes, cargo selection through receptors such as SQSTM1/p62, autophagosome-lysosome fusion, and lysosomal degradation. LC3 was identified as a mammalian homolog of yeast Atg8 that localizes to autophagosomal membranes after processing, and p62/SQSTM1 was shown to connect ubiquitinated cargo with autophagic degradati
-
Real Time qPCR (Q-PCR)
Real-time quantitative PCR (qPCR) quantifies an amplifiable nucleic-acid target by monitoring fluorescence during PCR cycling rather than measuring product only after amplification. The increase in fluorescence tracks accumulation of PCR product, and the quantification cycle (Cq; historically also Ct/CP) is related to the initial amount of target: samples containing more starting target generally reach the defined fluorescence threshold in fewer cycles.
-
Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)