LLC355
Based on 1 Customer Validation
LLC355 is a discoidin domain receptor 1 (DDR1) ATTEC degrader with a DC50 of 150.8 nM. LLC355 induces DDR1 protein degradation via lysosome-mediated autophagy. LLC355 inhibits the tumorigenicity, migration and invasion abilities of cancer cells, and induces apoptosis. LLC355 is applicable to research related to non-small cell lung cancer and pancreatic cancer.
(Pink: DDR1 ligand (HY-187093); Blue: LC3 ligand (HY-50759); Black: linker).
For research use only. We do not sell to patients.
- Purity : 99.71%
- Formula: C63H64ClF3N10O5
- Molecular Weight:1133.69
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Storage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vitro
Compound LLC355 (0.3-10000 nM; 1-24 h) dose- and time-dependently degrades DDR1 protein in NCI-H23 cells with a DC50 of 150.8 nM, without altering DDR2 levels[1].
Compound LLC355 (0.3 μM; 24 h) potently inhibits migration and invasion of NCI-H23 cells and reduces N-cadherin expression[1].
Compound LLC355 (0.1-1 μM; 10 days) potently suppresses colony formation of NCI-H23 cells over 10 days, with greater potency than DDR1 inhibitor 1[1].
Compound LLC355 (100-1000 nM; 24 h) does not induce apoptosis in NCI-H23 cells at 0.3 μM after 24 h treatment, but induces apoptosis at 1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:NCI-H23
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Concentration:0.3 μM (24 h); 1 μM (24 h); 1-10000 nM (12 h); 1 μM (1 h, 3 h, 6 h, 12 h, 24 h)
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Incubation Time:1 h, 3 h, 6 h, 12 h, 24 h
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Result:Induced 40% DDR1 degradation at 0.3 μM after 24 h treatment.
Induced 92% DDR1 degradation at 1 μM after 24 h treatment.
Dose-dependently degraded DDR1 with a DC50 value of 150.8 nM after 12 h treatment.
Time-dependently degraded DDR1 with maximal degradation observed at 24 h when treated with 1 μM.
Did not affect DDR2 protein levels at evaluated concentrations.
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Cell Line:PANC-1, MIA-PaCa-2
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Concentration:0.3 and 1 μM
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Incubation Time:24 h
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Result:Inhibited cell migration.
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Cell Line:PANC-1, MIA-PaCa-2
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Concentration:0.3 and 1 μM
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Incubation Time:24 h
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Result:Inhibited cell invasion.
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Cell Line:PANC-1, MIA-PaCa-2
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Concentration:0.1, 0.3 and 1 μM
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Incubation Time:24 h
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Result:Down-regulated the expression of N-Cadherin protein in a concentration-dependent manner.
Induced PARP cleavage in a concentration-dependent manner (i.e., promotes cell apoptosis).
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Cell Line:NCI-H23
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Concentration:0.1, 0.3 and 1 μM
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Incubation Time:10 days
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Result:Potently suppressed colony formation in NCI-H23 cells.
Parmacokinetics
Chemical Information
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Appearance Solid
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Molecular Weight 1133.69
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Formula C63H64ClF3N10O5
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Color White to light yellow
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SMILES
O=C1C2=CC=C(Cl)C=C2N=C([C@H](N(C(C3=CC=C(C)C=C3)=O)CCCNC(COCCN4CCN(CC5=CC(C(F)(F)F)=CC(NC(C6=CC(C#CC(C=N7)=CN8C7=CC=N8)=C(CC)C=C6)=O)=C5)CC4)=O)C(C)C)N1CC9=CC=CC=C9
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (88.21 mM; Need ultrasonic; 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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.21 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.21 mM); Suspended solution
This protocol yields a suspended solution of ≥ 2.5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
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.
Protocols
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Carcinogenicity Bioassay
A carcinogenicity bioassay detects whether long-term exposure to a test substance increases benign or malignant tumor incidence, changes tumor spectrum, or shortens tumor latency in experimental animals; the classical rodent design exposes rats and/or mice to multiple dose levels for most of their lifespan, followed by complete necropsy and histopathologic diagnosis of neoplastic and non-neoplastic lesions. The readout is tumor incidence by organ, sex, species, dose group, and survival status; interpretation requires concurrent controls, dose-response assessment, survival-adjusted tumor statistics, and pathology review because mortality, spontaneous tumor background, and body-weight effects can influence apparent tumor rates.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Cell migration
Cell migration is a method that plays an important role in wound healing, cell differentiation, embryonic development, etc.
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Autophagy
Autophagy is a process in which eukaryotic cells use lysosomes to degrade their own cytoplasmic proteins and damaged organelles under the regulation of autophagy related gene (Atg). Microtubule-associated proteins light chain 3 (LC3) is recognized as autophagy marker, which transfers from cytoplasmic LC3 (LC3-I) to membrane type (LC3-II). LC3-II/I ratio could be detected by Western Blot and fluorescence microscopy.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Cell invasion
Cell invasion is the ability of cells to migrate from one area to another via the extracellular matrix. Cell invasion is the response of normal and cancer cells to chemical and mechanical stimuli. Before migrating to a new region, the extracellular matrix is degraded by proteases within the cell. Cell invasion often occurs during wound repair, vascularization and inflammation, abnormal tissue invasion, and tumor cell metastasis.
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Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
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Soft Agar Colony Formation Assay
Soft agar colony formation assay measures anchorage-independent growth, in which transformed or tumorigenic cells proliferate as colonies in a semisolid agar matrix while many non-transformed adherent cells fail to proliferate without attachment; classic studies showed that growth in semisolid medium correlates with tumorigenicity in nude mice, and later protocol papers describe the method as a stringent in vitro assay for malignant transformation. The readout is the number, size, morphology, or signal intensity of colonies formed within agar after incubation; published formats include manual colony counting after staining, 96-well or 384-well quantitative formats, DNA-binding dye detection, MTT/tetrazolium-based detection, digital image analysis, and PCR-based marker detection from soft agar cultures.
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Macroautophagy Solutions
Macroautophagy is a conserved lysosome-dependent degradation pathway in which cytoplasmic material is sequestered into double-membrane autophagosomes and delivered to lysosomes for degradation and recycling. The pathway supports cellular homeostasis during nutrient limitation, organelle stress, protein-aggregate accumulation, infection, differentiation, and tissue remodeling by coupling cargo sequestration, autophagosome maturation, lysosomal fusion, and degradation of cargo-derived macromolecules. The core molecular sequence includes initiation by nutrient- and stress-regulated autophagy machinery, autophagosome nucleation, LC3/ATG8-family conjugation to autophagosomal membranes, cargo selection through receptors such as SQSTM1/p62, autophagosome-lysosome fusion, and lysosomal degradation. LC3 was identified as a mammalian homolog of yeast Atg8 that localizes to autophagosomal membranes after processing, and p62/SQSTM1 was shown to connect ubiquitinated cargo with autophagic degradati
Purity & Documentation
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Data Sheet (274 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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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. 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 |
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| DMSO | 1 mM | 0.8821 mL | 4.4104 mL | 8.8208 mL | 22.0519 mL |
| 5 mM | 0.1764 mL | 0.8821 mL | 1.7642 mL | 4.4104 mL | |
| 10 mM | 0.0882 mL | 0.4410 mL | 0.8821 mL | 2.2052 mL | |
| 15 mM | 0.0588 mL | 0.2940 mL | 0.5881 mL | 1.4701 mL | |
| 20 mM | 0.0441 mL | 0.2205 mL | 0.4410 mL | 1.1026 mL | |
| 25 mM | 0.0353 mL | 0.1764 mL | 0.3528 mL | 0.8821 mL | |
| 30 mM | 0.0294 mL | 0.1470 mL | 0.2940 mL | 0.7351 mL | |
| 40 mM | 0.0221 mL | 0.1103 mL | 0.2205 mL | 0.5513 mL | |
| 50 mM | 0.0176 mL | 0.0882 mL | 0.1764 mL | 0.4410 mL | |
| 60 mM | 0.0147 mL | 0.0735 mL | 0.1470 mL | 0.3675 mL | |
| 80 mM | 0.0110 mL | 0.0551 mL | 0.1103 mL | 0.2756 mL |
LLC355 Related Classifications
HY-162540 Related Classifications
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