2. Cell Cycle/DNA Damage Neuronal Signaling Autophagy
  3. Deubiquitinase PINK1/Parkin
  4. FT3967385

FT3967385 (FT385) is a selective covalent inhibitor that targets the outer mitochondrial membrane deubiquitinase (Deubiquitinase) USP30 (IC50 = 1.5 nM, Ki = 0.014 μM). By inhibiting the enzymatic activity of USP30, FT3967385 relieves its negative regulation of the PINK1-Parkin mediated mitochondrial ubiquitination cascade, thereby enhancing mitophagy. FT3967385 can be used for mechanistic studies of neurodegenerative diseases associated with mitochondrial dysfunction, such as Parkinson's disease.

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FT3967385

FT3967385 Chemical Structure

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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10 mM * 1 mL in DMSO In-stock
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FT3967385 Related Antibodies

Top Publications Citing Use of Products

View All Deubiquitinase Isoform Specific Products:

View All Isoforms
USP1 USP2 USP4 USP7 USP8 USP10 USP21 USP30 UCHL1 USP11 USP15 USP28 USP25

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

FT3967385 (FT385) is a selective covalent inhibitor that targets the outer mitochondrial membrane deubiquitinase (Deubiquitinase) USP30 (IC50 = 1.5 nM, Ki = 0.014 μM). By inhibiting the enzymatic activity of USP30, FT3967385 relieves its negative regulation of the PINK1-Parkin mediated mitochondrial ubiquitination cascade, thereby enhancing mitophagy. FT3967385 can be used for mechanistic studies of neurodegenerative diseases associated with mitochondrial dysfunction, such as Parkinson's disease[1][2][3].

In Vitro

FT3967385 (administered at concentrations ranging from 0 to 15000 nM for 30 min in the cell homogenate system; and at concentrations ranging from 0 to 625 nM for 4 h in the intact cell system) binds to endogenous USP30 in SH-SY5Y neuroblastoma cells at concentrations >100 nM[1].
FT3967385 (200 nM; 1-4 h) mimics the phenotype of USP30 knockout in hTERT-RPE1 YFP-Parkin cells by enhancing TOM20 ubiquitination after antimycin A and oligomycin A (AO)-induced mitochondrial depolarization, confirming its specific inhibitory effect on USP30[1].
FT3967385 (100-200 nM; 4-24 h) enhances the ubiquitination of TOM20 in SHSY5Y cells expressing endogenous Parkin after AO-induced mitochondrial depolarization[1].
FT3967385 (100-200 nM; 4-24 h) enhances the accumulation of phosphorylated Ser65, SYNJ2BP ubiquitin, and the ubiquitination of specific mitochondrial proteins (including members of the VDAC family) in depolarized SHSY5Y cells, thereby accelerating the PINK1-dependent signaling cascade of mitophagy[1].
FT3967385 (200-500 nM; 96 h) significantly increases the basal mitophagic flux in SHSY5Y-mitoQC cells over a 96 h treatment period[1].
Treatment with FT3967385 (200-500 nM; 96 h, administered once every 24 h) for 96 h enhances the basal mitophagic flux of SHSY5Y-mitoQC cells[2].

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

FT3967385 Related Antibodies

Western Blot Analysis[1]

Cell Line: SHSY5Y cells
Concentration: 0-15000 nM (cell homogenates); 0-625 nM (intact cells)
Incubation Time: 30 min ; 4 h
Result: Effectively competed with Ub-PA probe for binding to endogenous USP30 in SHSY5Y cells.
Showed significant target engagement at concentrations >100 nM in both cell homogenates and intact cells.

Western Blot Analysis[1]

Cell Line: hTERT-RPE1 cells overexpressing YFP-Parkin
Concentration: 200 nM
Incubation Time: 4 h, 1 h
Result: Enhanced ubiquitylation and apparent loss of TOM20 in response to AO treatment. Phenocopied USP30 knockout by promoting TOM20 ubiquitylation in parental cells, while no further enhancement was seen in USP30 knockout cells. Did not affect PINK1 protein levels.

Western Blot Analysis[1]

Cell Line: SHSY5Y cells expressing endogenous Parkin
Concentration: 200 nM (whole cell lysate analysis); 100 nM (mitochondrial fraction analysis)
Incubation Time: 1, 4, 24, 96 h
Result: Enhances TOM20 ubiquitylation in SHSY5Y cells expressing endogenous Parkin upon mitochondrial depolarisation with AO.
Molecular Weight

373.41

Formula

C21H19N5O2
Appearance

Solid

Color

White to off-white

SMILES

O=C(N[C@H]1CN(C#N)CC1)C2=CC(C3=C(OC4=CC=CC=C4)C=CC=C3)=NN2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (267.80 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.6780 mL 13.3901 mL 26.7802 mL
5 mM 0.5356 mL 2.6780 mL 5.3560 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Purity & Documentation

Purity: 99.74%

SDS (252 KB)

COA (249 KB) HNMR (123 KB) LCMS (103 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.6780 mL 13.3901 mL 26.7802 mL 66.9505 mL
5 mM 0.5356 mL 2.6780 mL 5.3560 mL 13.3901 mL
10 mM 0.2678 mL 1.3390 mL 2.6780 mL 6.6951 mL
15 mM 0.1785 mL 0.8927 mL 1.7853 mL 4.4634 mL
20 mM 0.1339 mL 0.6695 mL 1.3390 mL 3.3475 mL
25 mM 0.1071 mL 0.5356 mL 1.0712 mL 2.6780 mL
30 mM 0.0893 mL 0.4463 mL 0.8927 mL 2.2317 mL
40 mM 0.0670 mL 0.3348 mL 0.6695 mL 1.6738 mL
50 mM 0.0536 mL 0.2678 mL 0.5356 mL 1.3390 mL
60 mM 0.0446 mL 0.2232 mL 0.4463 mL 1.1158 mL
80 mM 0.0335 mL 0.1674 mL 0.3348 mL 0.8369 mL
100 mM 0.0268 mL 0.1339 mL 0.2678 mL 0.6695 mL
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FT3967385 Related Classifications

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:

FT3967385FT385FT 3967385FT-3967385FT 385FT-385DeubiquitinasePINK1/ParkinDUBsPTEN-induced kinase 1/ParkinUSP30 InhibitorSHSY5Y cellshTERT-RPE1 cellsParkinson's disease
Inhibitorinhibitorinhibit

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