NCATS-SM0225
NCATS-SM0225 is an endoplasmic reticulum-associated degradation (ERAD) inhibitor and a direct binder of VDAC1, VDAC2 and VDAC3. NCATS-SM0225 exhibits an IC50of 1.02 μM for ERAD and a Kd of 3.13 μM for human VDAC1 binding. NCATS-SM0225 disrupts cellular calcium homeostasis, enhances VDAC1-IP3R coupling and activating PERK. NCATS-SM0225 selectively kills cancer cells, exhibits tumor growth inhibitory effects in melanoma xenograft models. NCATS-SM0225 can be used for research on multiple cancers including melanoma, as well as the molecular mechanisms of ERAD and calcium homeostasis regulation.
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- No. CAS: 1212623-02-3
- Fòrmula: C23H28N2O4S2
- Peso molecular:460.61
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Almacenamiento:
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Actividad biológica
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VDAC1 3.13 μM (Kd) |
VDAC2 |
VDAC3 |
NCATS-SM0225 (0-12800 nM; 30 min) directly binds to recombinant human VDAC1 with a Kd of 3.13 μM.
NCATS-SM0225 (2 μM; 1 h) engages with all three VDAC1, VDAC2, VDAC3 in HeLa cells, as evidenced by enhanced thermal stability of the VDAC proteins[1].
NCATS-SM0225 (100-400 nM) modulates VDAC1 channel function by promoting voltage-dependent closure at lower negative potentials, with a functional IC50 of 140 nM[1].
NCATS-SM0225 (0.625-5 μM; 6 h) potently inhibits ER dislocation in HeLa cells with an IC50 of 1.02 μM, as measured by the NHK-drGFP reporter assay[1].
NCATS-SM0225 (0.625-5 μM; 6-22 h) elevates calcium levels in mitochondria, cytosol, and ER in HeLa cells in a VDAC-dependent manner, with effects enhanced by higher concentrations and longer incubation times[1].
NCATS-SM0225 (0-10 μM; 40-48 h) selectively induces apoptotic cell death in a subset of cancer cell lines while sparing normal cells, with selectivity correlating with its ability to disrupt calcium homeostasis and degrade ERAD complex proteins[1].
NCATS-SM0225 (1.25-10 μM; 6-24 h) induces selective degradation of ERAD complex proteins (HERP1, OS9, FAM8A1) in HeLa cells in a dose- and time-dependent, Ca2+-dependent manner, while activating PERK signaling[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HeLa, Huh7, A375, U251, U87, PSN1, U2OS, MCF7ca, A253, BT474, MDA-MB-231, SKBR-3, T47D, MDA-MB-453, primary fibroblasts HDFa, GM05294, GM04390, primary melanocytes HEMa, primary hepatocytes
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Concentration:0, 2, 4, 6, 8, 10 μM
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Incubation Time:48 h
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Result:Selectively induced cell death in a subset of cancer cell lines (HeLa, Huh7, A375, U251, U87, PSN1, U2OS, MCF7ca, A253, BT474) with significant viability reduction.
Caused minimal to no viability effect on insensitive cancer cell lines (MDA-MB-231, SKBR-3, T47D, MDA-MB-453) and normal cells up to 10 μM.
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Cell Line:HeLa cells
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Concentration:1.25, 2.5, 5, 10 μM
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Incubation Time:6 h; 24 h
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Result:Reduced HERP1, OS9, and FAM8A1 protein levels in a dose-dependent manner.
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Cell Line:HeLa cells
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Concentration:1.25, 2.5, 5 μM
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Incubation Time:6 h
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Result:Induced phosphorylation of PERK.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male BALB/c-nu nude mice (7 weeks old) were subcutaneously injected with A375 human melanoma cells (2 × 106 cells per mouse) which were suspended in a 1:1 mixture with Matrigel into the right flank[1]
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Dosage:20 mg/kg
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Administration:intraperitoneal injection; once daily for 14 days
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Result:Markedly inhibited tumor growth.
Showed no clinical signs of adverse effects.
Revealed no abnormalities in histological examination of the liver, pancreas, and kidney.
Chemical Information
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No. CAS 1212623-02-3
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Peso molecular 460.61
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Fòrmula C23H28N2O4S2
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SMILES
O=S(CC1=CC=CC=C1)(NC2=NC([C@@H](C)[C@]3([H])[C@](OC([C@H]4C)=O)([H])[C@@]4([H])CC[C@@]3(C)C5)=C5S2)=O
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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)
NCATS-SM0225 Related Classifications
HY-181529 Related Classifications
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- NCATS-SM0225
- 1212623-02-3
- VDAC
- PERK
- ERAD inhibitor
- VDAC1/2/3 direct binder
- PERK activator
- selective anticancer activity
- calcium homeostasis disruptor
- ER-phagy activator
- melanoma
- glioma
- breast cancer
- liver cancer
- pancreatic cancer
- A375 cells
- U-251 MG cells
- U-87 MG cells
- MDA-MB-231 cells
- HepG2 cells
- Huh7 cells
- PSN1 cells
- MIAPaCa-2 cells
- U-2OS cells
- A253 cells
- melanoma xenograft model
- Inhibitor
- inhibitor
- inhibit