2. Membrane Transporter/Ion Channel Cell Cycle/DNA Damage
  3. VDAC PERK
  4. 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.

For research use only. We do not sell to patients.

NCATS-SM0225

NCATS-SM0225 Chemical Structure

CAS No. : 1212623-02-3

Size Stock
50 mg   Get quote  
100 mg   Get quote  
250 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

NCATS-SM0225 Related Antibodies

Top Publications Citing Use of Products

View All VDAC Isoform Specific Products:

View All Isoforms
VDAC1 VDAC2 VDAC3

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

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[1].

IC50 & Target[1]

VDAC1

3.13 μM (Kd)

VDAC2

 

VDAC3

 

In Vitro

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.

NCATS-SM0225 Related Antibodies

Cell Viability Assay[1]

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
Concentration: 0, 2, 4, 6, 8, 10 μM
Incubation Time: 48 h
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.

Western Blot Analysis[1]

Cell Line: HeLa cells
Concentration: 1.25, 2.5, 5, 10 μM
Incubation Time: 6 h; 24 h
Result: Reduced HERP1, OS9, and FAM8A1 protein levels in a dose-dependent manner.

Western Blot Analysis[1]

Cell Line: HeLa cells
Concentration: 1.25, 2.5, 5 μM
Incubation Time: 6 h
Result: Induced phosphorylation of PERK.
In Vivo

NCATS-SM0225 (20 mg/kg; intraperitoneal injection; daily for 14 days) can significantly inhibit the growth of A375 melanoma xenografts in male BALB/c-nu mice with no detectable toxicity[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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]
Dosage: 20 mg/kg
Administration: intraperitoneal injection; once daily for 14 days
Result: Markedly inhibited tumor growth.
Showed no clinical signs of adverse effects.
Revealed no abnormalities in histological examination of the liver, pancreas, and kidney.
Molecular Weight

460.61

Formula

C23H28N2O4S2
CAS No.
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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

NCATS-SM0225 Related Classifications

  • Molarity Calculator

  • Dilution Calculator

The molarity calculator equation

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass   Concentration   Volume   Molecular Weight *
= × ×

The dilution calculator equation

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
× = ×
C1   V1   C2   V2
Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NCATS-SM02251212623-02-3VDACPERKVoltage-dependent anion channel Protein kinase R-like endoplasmic reticulum kinasePKR-like endoplasmic reticulum kinaseERAD inhibitorVDAC1/2/3 direct binderPERK activatorselective anticancer activitycalcium homeostasis disruptorER-phagy activatormelanomagliomabreast cancerliver cancerpancreatic cancerA375 cellsU-251 MG cellsU-87 MG cellsMDA-MB-231 cellsHepG2 cellsHuh7 cellsPSN1 cellsMIAPaCa-2 cellsU-2OS cellsA253 cellsmelanoma xenograft modelInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Requested Quantity *

Applicant Name *

 

Salutation

Email Address *

 

Phone Number *

Department

 

Organization Name *

City

State

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
NCATS-SM0225
Cat. No.:
HY-181529
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

SAFETY DATA SHEET (SDS)

Request for HNMR Report

We have received your request and will respond to you as soon as possible.