17β-HSD10-IN-4
17β-HSD10-IN-4 is a selective brain-penetrant 17β-HSD10 inhibitor with an IC50 of 6.33 μM. 17β-HSD10-IN-4 forms key interactions with the 17β-HSD10 catalytic triad to functionally inhibit the enzyme, without altering its protein levels. 17β-HSD10-IN-4 restores mitochondrial function, reduces ROS levels, increases ATP production, and suppresses cytochrome c release. 17β-HSD10-IN-4 attenuates CDK5/p25 activation, reduces Tau hyperphosphorylation, Aβ plaque load and restores brain-derived neurotrophic factor levels. 17β-HSD10-IN-4 improves cognitive function.17β-HSD10-IN-4 can be used for the research of Alzheimer's disease.
For research use only. We do not sell to patients.
- Formula: C14H12N2O3S
- Molecular Weight:288.32
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All 17β-HSD Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
17β-HSD10 6.33 μM (IC50) |
Cdk5/p25 |
In Vitro
17β-HSD10-IN-4 (Compound 14) (24 h) potently inhibits 17β-HSD10 activity in pCMV-Neo_17β-HSD10-transfected HEK-293 cells with an IC50 of 6.33 ± 0.15 μM[1].
17β-HSD10-IN-4 (10 h) exhibits favorable blood-brain barrier permeability with a Pe value of 4.75 ± 0.31 × 10-6 cm·s-1, qualifying it as CNS-permeable[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (B6) APPswe/PSEN1dE9 (APP/PS1) transgenic (male, 6 months old)[1]
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Dosage:10 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Improved spatial learning and memory, with treated mice spending 29 seconds in the target quadrant during the Morris water maze probe trial, demonstrating reduced escape latency, increased platform crossings, and goal-directed swimming trajectories.
Reduced cerebral reactive oxygen species (ROS) levels by 24% and increased ATP content by 76% in APP/PS1 mouse brain cells; suppressed cytochrome c release to near wild-type levels.
Reduced cortical phosphorylated Tau (p-Tau) levels by 32% and cortical p-Tau/Tau ratio by 18%; reduced hippocampal p-Tau levels by 18% and hippocampal p-Tau/Tau ratio by 11%; reduced CDK5 overexpression by 13% in the cortex and 7% in the hippocampus.
Increased cortical brain-derived neurotrophic factor (BDNF) levels by 58% compared to untreated APP/PS1 mice, restoring levels to near wild-type values.
Reduced cerebral Aβ plaque load by approximately two-thirds (plaque burden was one-third of that in untreated APP/PS1 mice).
Showed no significant change in 17β-HSD10 protein expression relative to untreated APP/PS1 mice.
Chemical Information
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Molecular Weight 288.32
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Formula C14H12N2O3S
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SMILES
O=C1C2=C(C(C3=C1N=C(S3)NCCCO)=O)C=CC=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Mitochondrial membrane-potential fluorescent assay
Mitochondrial membrane potential fluorescent assays estimate ΔΨm in living cells using lipophilic cationic dyes such as TMRM, TMRE, rhodamine 123, and JC-1, which accumulate in mitochondria according to membrane polarization; loss of signal after FCCP or CCCP treatment is interpreted as mitochondrial depolarization. TMRM/TMRE and rhodamine 123 are commonly used for semi-quantitative live-cell microscopy or flow cytometry, while JC-1 can report a shift from red aggregate fluorescence to green monomer fluorescence during depolarization; interpretation requires controls because dye concentration, quenching mode, cell type, dye efflux, and mitochondrial mass can affect fluorescence independently of ΔΨm.
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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.
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ROS/oxidative-stress fluorescent staining
ROS/oxidative-stress fluorescent staining uses cell-permeant fluorogenic probes that become fluorescent after oxidation inside cells or tissues; commonly used examples include DCFH-DA/DCFDA for broad cellular oxidant detection, DHE for superoxide-related signal detection, MitoSOX for mitochondrial superoxide-related signal detection, and CellROX probes for oxidative-stress-associated fluorescence readouts. The assay detects probe oxidation rather than a single ROS species unless the probe and analysis method have been chemically validated for that species. DCFH-DA enters cells, is deacetylated by intracellular esterases to DCFH, and produces fluorescent DCF after oxidation, so the readout is used as an operational measure of total cellular oxidative stress rather than a species-specific ROS measurement. DHE and MitoSOX can report superoxide-related oxidation, but red fluorescence alone can include non-specific ethidium-like oxidation products; HPLC or optimized spectral approaches are
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Mitochondrial membrane-potential and mitochondrial mass staining
Mitochondrial membrane potential staining measures the electrochemical polarization across the mitochondrial inner membrane in live cells using lipophilic cationic fluorescent probes; early rhodamine-based work showed that selective mitochondrial dye accumulation is lost when the mitochondrial transmembrane potential is dissipated. JC-1 reports mitochondrial polarization by shifting from green monomer fluorescence to red J-aggregate fluorescence as dye concentration increases within energized mitochondria; therefore, the red/green fluorescence ratio is used as a relative readout of mitochondrial membrane potential. TMRE or TMRM staining provides a single-channel relative readout because these cationic rhodamine esters accumulate in polarized mitochondria, and lower fluorescence indicates reduced mitochondrial polarization when acquisition and dye-loading conditions are controlled. Mitochondrial mass staining is commonly performed with MitoTracker Green FM or related MitoTracker dyes as
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Protocol for Water Maze
The Morris Water Maze is a rodent spatial learning and memory assay in which a mouse or rat swims in opaque water to find an escape platform; in the hidden-platform version, the animal cannot see the platform and must use distal extra-maze cues to learn its fixed spatial location. The assay primarily measures hippocampus-dependent spatial learning during acquisition trials and spatial reference memory during probe trials after platform removal; readouts include escape latency, swim path length, swim speed, quadrant occupancy, platform-site crossings, and proximity to the former platform location.
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)