KUS187
KUS187 is an orally active VCP ATPase modulator that inhibits VCP ATPase activity and reduces cellular ATP consumption. KUS187 prevents MPP+, low Glucose (D-Glucose) (HY-B0389)-, and Tunicamycin (HY-A0098)-induced cytoplasmic and mitochondrial ATP depletion. KUS187 inhibits ER stress, suppresses AMPK activation, prevents loss of mitochondrial membrane potential and changes in mitophagy, and protects neurons from MPP+-induced death/neurite retraction. KUS187 can be used for research on Parkinson's disease, retinitis pigmentosa, and retinal ganglion cell injury.
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- No. CAS: 1357164-95-4
- Fòrmula: C27H25N4NaO5S
- Peso molecular:540.57
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
Descripciòn
In Vitro
KUS187 (50 μM; 24 h) preserves mitochondrial morphology, neurite mitochondrial length, and mitochondrial membrane potential in PC12 cells exposed to MPP+, but does not increase mitochondrial mass or reduce ROS[1].
KUS187 (25 μM; 24 h) protects primary midbrain dopaminergic neurons from MPP+-induced death and neurite atrophy[1].
KUS187 (30-1000 nM; 20 min) inhibits recombinant human VCP ATPase activity with an IC50 of 186 nM[2].
KUS187 (100 nM-1 mM; 20 min) decreased total soluble ATPase activity in lysates of neuronally differentiated PC12 cells, by approximately 20% at 100 nM and approximately 40% at 1 mM[2].
KUS187 (20 μM; 41 h) protects HeLa cells from Glucose-induced cell death[2].
KUS187 (20 μM; 41 h) protects HeLa cells from Tunicamycin-induced cell death[2].
KUS187 (50 μM; 5 h) prevents Tunicamycin-induced laminin c1 aggregation in HeLa cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Neuronally differentiated PC12 cells
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Concentration:50 μM
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Incubation Time:24 h
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Result:Preserved mitochondrial morphology, neurite mitochondrial length, and mitochondrial membrane potential in PC12 cells exposed to MPP+.
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Cell Line:HeLa cells
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Concentration:20 μM
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Incubation Time:41 h
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Result:Prevented low-Glucose-induced HeLa cell death.
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Cell Line:HeLa cells
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Concentration:20 μM
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Incubation Time:41 h
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Result:Protected HeLa cells from Tunicamycin-induced cell death.
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Cell Line:HeLa cells
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Concentration:50 μM
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Incubation Time:5 h
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Result:Suppressed Tunicamycin-induced CHOP and Grp78 expression and restored Akt phosphorylation at Ser473.
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Cell Line:HeLa cells
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Concentration:50 μM
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Incubation Time:5 h
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Result:Prevented Tunicamycin-induced aggregation of laminin c1.
Remained in a diffuse ER pattern.
In Vivo
KUS187 (50 mg/kg/day; oral; once daily; 7 days) alters retinal endothelin-related gene expression in C57/BL6 wild-type and B6.Cg-Tg (Ty1-CFP) 23Jrs/J mice with NMDA (HY-17551)-induced acute retinal ganglion cell injury, and shows lower EDN1/EDNRB immunostaining in the RGC layer relative to NMDA-injected controls[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 rd10 (PDE6B mutant; age P7-P33)[2]
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Dosage:50 mg/kg
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Administration:i.p.; once daily; starting 7 days after birth
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Result:Detected ONL and inner segment/outer segment junction line at P25 in KUS187-administered rd10 mice.
Showed almost normal electroretinography response in most KUS187-administered rd10 mice at P25.
Preserved thin ONL and electroretinography response at P29 in KUS187-administered rd10 mice.
Showed 5-6 ONL rows, observable photoreceptor outer segments, and small b-wave and oscillatory potentials at P33 in KUS187-administered rd10 mice.
Delayed disease progression based on time-dependent total retinal thickness and dark-adapted b-wave amplitudes.
Showed regularly arranged photoreceptor outer segments at P21 in KUS187-administered rd10 retinas.
Suppressed retinal CHOP expression at P21 in KUS187-administered rd10 mice.
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Animal Model:C57/BL6 wild-type and B6.Cg-Tg(Ty1-CFP)23Jrs/J (male; 2-3 months old; NMDA-induced acute retinal ganglion cell damage)[3]
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Dosage:50 mg/kg/day
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Administration:p.o. (feeding tube); once daily; 7 days
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Result:Showed higher Edn1 mRNA expression in neural retina in NMDA-injected KUS187-treated mice (n=8) than in non-treated wild-type mice (n=7).
Showed higher Ednrb mRNA expression in NMDA-injected control mice than in non-treated wild-type mice, whereas Ednrb mRNA expression in NMDA-injected KUS187-treated mice did not differ from non-treated wild-type mice.
Showed no difference in Ednra mRNA expression among groups.
Downregulated 136 transcripts (95 genes) <0.5-fold by KUS187 administration relative to NMDA-saline among 387 transcripts upregulated >2-fold by NMDA-saline.
Upregulated 93 transcripts (74 genes) >2-fold by KUS187 administration relative to NMDA-saline among 335 transcripts downregulated <0.5-fold by NMDA-saline.
Showed lower EDN1 and EDNRB protein expression in the RGC layer in NMDA-injected KUS187-treated mice (n=2) than in NMDA-injected control mice (n=3) by immunostaining of retinal sections.
Chemical Information
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No. CAS 1357164-95-4
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Peso molecular 540.57
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Fòrmula C27H25N4NaO5S
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SMILES
O=CC1=CC(C)=CC(C2=NC=C(C=C2)/N=N/C3=C(N)C4=C(C=CC=C4)C(S(=O)(O[Na])=O)=C3)=C1OCCCC
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KUS187 Related Classifications
HY-134499 Related Classifications
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