LDN-57444
Based on 20 publication(s) in Google Scholar
LDN-57444 is a reversible, competitive and site-directed inhibitor of ubiquitin C-terminal hydrolase L1 (UCH-L1), with an IC50 of 0.88 μM and a Ki of 0.40 μM; LDN-57444 also suppresses UCH-L3 activity, with an IC50 of 25 μM.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 99.21%
- CAS 番号: 668467-91-2
- 分子式: C17H11Cl3N2O3
- 分子量:397.64
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
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Help & FAQs
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MedChemExpress（MCE）の使用を引用している文献 LDN-57444
More- Nat Commun. 2025 May 16;16(1):4564. [Abstract]
- Nat Commun. 2022 Mar 31;13(1):1700. [Abstract]
- Redox Biol. 2026 May:92:104086. [Abstract]
- J Immunother Cancer. 2026 Jan 14;14(1):e013498. [Abstract]
- Cell Chem Biol. 2021 Jun 17;28(6):855-865.e9. [Abstract]
- EMBO J. 2022 Aug 16;41(16):e108791. [Abstract]
- J Med Chem. 2022 Oct 27;65(20):13645-13659. [Abstract]
- Hypertens Res. 2020 Mar;43(3):168-177. [Abstract]
- Cancer Sci. 2020 Sep;111(9):3174-3183. [Abstract]
- Sci Rep. 2020 Jun 30;10(1):10604. [Abstract]
- Cancers (Basel). 2024 Oct 31;16(21):3683. [Abstract]
- FASEB J. 2021 Aug;35(8):e21800. [Abstract]
- Anim Cells Syst. 2024 May 11;28(1):237-250. [Abstract]
- Mol Oral Microbiol. 2026 Aug;41(4):201-215. [Abstract]
- Exp Dermatol. 2024 Oct;33(10):e15186. [Abstract]
- Biochem Biophys Res Commun. 2018 Mar 4;497(2):726-733. [Abstract]
- J Surg Oncol. 2017 Jun;115(8):932-940. [Abstract]
- Int J Clin Exp Med. 2016;9(8):15561-15567.
- bioRxiv. 2026 May 19.
- Washington University. 2025.
Customer Validation & Images
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生物活性
IC50: 0.88 μM (UCH-L1), 25 μM (UCH-L3)[1]
Ki: 0.40 μM (UCH-L1)[1]
LDN-57444 is a reversible, competitive inhibitor of UCH-L1, with an IC50 of 0.88 μM, and also suppresses UCH-L3 activity, with an IC50 of 25 μM[1]. LDN-57444 (LDN, 5 μM for 1 hr) inhibits 70% of Uch activity in hippocampal slices of the mouse brain. LDN-57444 (5 μM for 2 hr) does not reduce potentiation further in APP/PS1 slices or in wt slices exposed to 200 nM Aβ[2]. LDN-57444 (25-100 μM) inhibits ubiquitin-proteasome activity dose-dependently in SK-N-SH cells. LDN-57444 (50 μM) also induces apoptotic cell death, causes the endoplasmic reticulum stress and results in expression of spliced XBP-1(XBP-1s, 48KD) in SK-N-SH cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
化学情報
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CAS 番号 668467-91-2
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性状 Solid
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分子量 397.64
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分子式 C17H11Cl3N2O3
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Color Light yellow to yellow
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SMILES
O=C1N(CC2=CC(Cl)=CC=C2Cl)C3=C(C=C(Cl)C=C3)/C1=N/OC(C)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Publications (20)
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Journal Impact Factor
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Most Recent
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Nat Commun
2025 May 16;16(1):4564. PMID: 40379682 -
Nat Commun
USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy. [Abstract]2022 Mar 31;13(1):1700. PMID: 35361799 -
Redox Biol
USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers. [Abstract]2026 May:92:104086. PMID: 41844497 -
J Immunother Cancer
CD47 destabilization via manipulating the SPOP-USP2 axis augments macrophage phagocytosis and cancer immunotherapy. [Abstract]2026 Jan 14;14(1):e013498. PMID: 41534899 -
Cell Chem Biol
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2. [Abstract]2021 Jun 17;28(6):855-865.e9. PMID: 33979649 -
EMBO J
USP8 promotes cancer progression and extracellular vesicle-mediated CD8+ T cell exhaustion by deubiquitinating the TGF-β receptor TβRII. [Abstract]2022 Aug 16;41(16):e108791. PMID: 35811497 -
J Med Chem
Discovery of Potent OTUB1/USP8 Dual Inhibitors Targeting Proteostasis in Non-Small-Cell Lung Cancer. [Abstract]2022 Oct 27;65(20):13645-13659. PMID: 36221183 -
Hypertens Res
2020 Mar;43(3):168-177. PMID: 31700166 -
Cancer Sci
Ubiquitin C-terminal hydrolase L1 promotes expression of programmed cell death-ligand 1 in non-small-cell lung cancer cells. [Abstract]2020 Sep;111(9):3174-3183. PMID: 32539182 -
Sci Rep
Ubiquitin C-terminal hydrolase L1 (UCHL1) regulates post-myocardial infarction cardiac fibrosis through glucose-regulated protein of 78 kDa (GRP78). [Abstract]2020 Jun 30;10(1):10604. PMID: 32606430 -
Cancers (Basel)
Integrin α6β4 Upregulates PTPRZ1 Through UCHL1-Mediated Hif-1α Nuclear Accumulation to Promote Triple-Negative Breast Cancer Cell Invasive Properties. [Abstract]2024 Oct 31;16(21):3683. PMID: 39518121 -
FASEB J
2021 Aug;35(8):e21800. PMID: 34324733 -
Anim Cells Syst
Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells. [Abstract]2024 May 11;28(1):237-250. PMID: 38741950 -
Mol Oral Microbiol
UCHL1 Exacerbates Periodontitis by Coordinating Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Macrophages. [Abstract]2026 Aug;41(4):201-215. PMID: 41919688 -
Exp Dermatol
Inhibition of Ubiquitin C-Terminal Hydrolase L1 Facilitates Cutaneous Wound Healing via Activating TGF-β/Smad Signalling Pathway in Fibroblasts. [Abstract]2024 Oct;33(10):e15186. PMID: 39367569 -
Biochem Biophys Res Commun
Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity. [Abstract]2018 Mar 4;497(2):726-733. PMID: 29462615
LDN-57444 purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2018 Mar 4;497(2):726-733. [Abstract]
Drug screen of UCHL1 and the function of inhibitors in autophagy. Both LDN and NSC could inhibit UCHL1 hydrolase activity. mRFP-GFP-LC3 stable cell line is treated with 5 μM LDN or 10 μM NSC in the condition of DMSO or Torin1 respectively for 6 h. The number of LC3 puncta remarkably is raised both in LDN and NSC treatment cells compared to the control.
LDN-57444 purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2018 Mar 4;497(2):726-733. [Abstract]
Drug screen of UCHL1 and the function of inhibitors in autophagy. Both LDN and NSC could inhibit UCHL1 hydrolase activity. Each cell lysate is analyzed by immunoblotting with anti p62 and LC3 antibodies.
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J Surg Oncol
UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer. [Abstract]2017 Jun;115(8):932-940. PMID: 28334432
LDN-57444 purchased from MedChemExpress. Usage Cited in: J Surg Oncol. 2017 Jun;115(8):932-940. [Abstract]
p-ERK1/2 and ERK1/2 P-gp protein level are assessed by Western blot.
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溶剤 & 溶解度
DMSO : 25 mg/mL (62.87 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 10 mg/mL (25.15 mM); Suspended solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
プロトコル
To start an assay, 0.5 μL of 5 mg/mL test compound (including LDN-57444, about 50 μM final reaction concentration) or DMSO control is aliquoted into each well. Both enzyme and substrate are prepared in UCH reaction buffer (50 mM Tris-HCl [pH 7.6], 0.5 mM EDTA, 5 mM DTT, and 0.5 mg/mL ovalbumin). 25 μL of 0.6 nM UCH-L1 is then added to each well except substrate control wells, followed by plate shaking for 45-60 s on an automatic shaker. The enzyme/compound mixture is incubated at room temperature for 30 min before 25 μL of 200 nM Ub-AMC is added to initiate the enzyme reaction. The reaction mixture (300 pM UCH-L1, 100 nM Ubiquitin-AMC with 2.5 μg test compound) is incubated at room temperature for 30 additional minutes prior to quenching the reaction by the addition of 10 μL 500 mM acetic acid per well. The fluorescence emission intensity is measured on a LJL Analyst using a coumarin filter set (ex = 365 nm, em = 450 nm) and is subtracted by the intrinsic compound fluorescence to reveal the enzyme activity. A DMSO control (0.5 μL of DMSO, 25 μL of UCH-L1, 25 μL of ubiquitin-AMC, 10 μL of acetic acid), enzyme control (25 μL of UCH-L1, 25 μL of buffer, 10 μL of acetic acid), substrate control (25 μL of buffer, 25 μL of ubiquitin-AMC, 10 μL of acetic acid), and inhibitor control (0.5 μL of ubiquitin aldehyde [100 nM stock], 25 μL of UCH-L1, 25 μL of ubiquitin-AMC, 10 μL of acetic acid) are also performed in each assay plate to ensure quality and reproducibility. The UCH-L1 enzymatic reactions are manually repeated twice using the same protocol to confirm the results for the hit compounds from the primary robot-assisted screen[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Cell viability is measured by a quantitative colorimetric assay with MTT. After drug treatment SK-N-SH cells are incubated for 4 h with 5 g/L MTT and then DMSO is added for 15 min. The absorption is quantified at 570 nm using a micro-plate reader[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Each animal is placed individually into the conditioning chamber. The electric current is gradually increased (0.1 mA for 1 sec. at 30 sec. intervals increasing the shock intensity by 0.1 mA to 0.7 mA). Animal behavior is evaluated for the first visible response to the shock (flinch), the first extreme motor response (run/jump), and the first vocalized distress (scream). Threshold to flinching, jumping, and screaming is quantified for each animal by averaging of the shock intensity at which each animal manifests a behavioral response of that type to the foot shock. Visual, motor, and motivation skills are also tested with visible platform training by measuring the time and the speed to reach a visible platform placed within a pool filled with water. Both time to reach the platform and swimming speed are recorded and analyzed with a video tracking system. No difference is observed among different groups of mice in the experiments in which fear conditioning is tested both in the presence of LDN-57444 (LDN) and TAT fusion proteins. To decide the time of administration of LDN-57444, a series of preliminary experiments are performed in which the inhibitor is injected intra-peritoneally at different intervals (4 hrs before, 1 hr before, 1 hr after and 4 hrs after) from the electric shock. During the training phase, there is no difference in the freezing of LDN-57444- or vehicle-injected mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
純度とドキュメンテーション
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データシート (286 KB)
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参考文献
[1]. Liu Y, et al. Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line. Chem Biol. 2003 Sep;10(9):837-46. [Content Brief]
[2]. Gong B, et al. Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug 25;126(4):775-88. [Content Brief]
[3]. Tan YY, et al. Endoplasmic reticulum stress contributes to the cell death induced by UCH-L1 inhibitor. Mol Cell Biochem. 2008 Nov;318(1-2):109-15. [Content Brief]
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. 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 | 2.5148 mL | 12.5742 mL | 25.1484 mL | 62.8709 mL |
| 5 mM | 0.5030 mL | 2.5148 mL | 5.0297 mL | 12.5742 mL | |
| 10 mM | 0.2515 mL | 1.2574 mL | 2.5148 mL | 6.2871 mL | |
| 15 mM | 0.1677 mL | 0.8383 mL | 1.6766 mL | 4.1914 mL | |
| 20 mM | 0.1257 mL | 0.6287 mL | 1.2574 mL | 3.1435 mL | |
| 25 mM | 0.1006 mL | 0.5030 mL | 1.0059 mL | 2.5148 mL | |
| 30 mM | 0.0838 mL | 0.4191 mL | 0.8383 mL | 2.0957 mL | |
| 40 mM | 0.0629 mL | 0.3144 mL | 0.6287 mL | 1.5718 mL | |
| 50 mM | 0.0503 mL | 0.2515 mL | 0.5030 mL | 1.2574 mL | |
| 60 mM | 0.0419 mL | 0.2096 mL | 0.4191 mL | 1.0478 mL |
LDN-57444 関連分類
HY-18637 関連分類
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