TD-004
Based on 1 Customer Validation
TD-004 is a potent ALK PROTAC degrader. TD-004 exhibits anti-ALK inhibitory activity with an IC50 of 0.11 µM and selectively inhibits the proliferation of SU-DHL-1 and H3122 cells (ALK-positive cancer cells) with IC50s of 0.058 µM and 0.28 µM, respectively. TD-004 induces degradation of ALK fusion proteins (NPM-ALK and EML4-ALK) via recruitment of the VHL E3 ligase and the proteasome pathway. TD-004 demonstrates significant tumor growth inhibition with a favorable safety profile in vivo. TD-004 can be used for the research of anaplastic large cell lymphoma and non-small cell lung cancer.
(Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-15656); Blue: VHL ligand (HY-125845); Black: linker).
For research use only. We do not sell to patients.
- Purity : 99.42%
- CAS No.: 2162120-55-8
- Formula: C55H70ClN9O8S2
- Molecular Weight:1084.78
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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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
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Biological Activity
Description
IC50 & Target
[1]|
VHL |
In Vitro
TD-004 exhibits anti-ALK activities with an IC50 of 0.11 μM, binds VHL with micromolar affinities.
TD-004 (1 μM) degrades NPM-ALK protein with 93% in SU-DHL-1, this degradation effectivity is not correlated with ALK inhibitory activity[1].
TD-004 (0.03-30 µM, 8-16 h) degrades fusion protein EML4-ALK in NCI-H3122 cell lines in time and dose dependent manner[1].
TD-004 (0.2-3 μM, 1-16 h) effectively induces the intracellular fusion ALK degradation by E3 ligase VHL in H3122 cell and proteasome mediated mechanism in SU-DHL-1 cells[1].
TD-004 (3 days) selectively inhibits the cell proliferation of SU-DHL-1, H3122 cancer cells (ALK positive cancer cell lines) with IC50s of 0.058 μM,0.28 μM, but not inhibits A549 cells (IC50 > 10 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-H3122 cell
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Concentration:0.03, 0.3, 3 and 30 μM
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Incubation Time:8 or 16 h
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Result:Degraded fusion protein EML4-ALK in dose-dependent manner for 16 h.
Slightly reduced ALK level at 8h treatment at high concentration, which indicated a time-dependent degradation pattern.
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Cell Line:H3122 cells
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Concentration:0.3 and 3 μM
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Incubation Time:1 h
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Result:Induced ALK degradation, which was blocked by co-treatment with Epoxomicin (HY-13821) (1 μM).
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Cell Line:SU-DHL-1 cells
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Concentration:0.2 μM
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Incubation Time:16 h
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Result:Mediated degradation of the NPM-ALK protein, which was inhibited by the VHL ligand.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:H3122 cells (ALK-positive cells) (5 x 10 6) induced-female BALB/c nude mice[1].
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Dosage:58 mg/kg
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Administration:i.p., once daily for 14 days
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Result:Reduced tumor volume.
Did Not affect body weight.
Chemical Information
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CAS No. 2162120-55-8
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Appearance Solid
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Molecular Weight 1084.78
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Formula C55H70ClN9O8S2
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Color White to off-white
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SMILES
CC(C)OC(C=C(C1CCN(CC1)C(CCCC(N[C@@H](C(C)(C)C)C(N2[C@@H](C[C@H](C2)O)C(NCC3=CC=C(C4=C(N=CS4)C)C=C3)=O)=O)=O)=O)C(C)=C5)=C5NC6=NC=C(Cl)C(NC7=C(C=CC=C7)S(C(C)C)(=O)=O)=N6
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (92.18 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 (sealed storage, away from moisture). 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 (sealed storage, away from moisture). 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 (2.30 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.
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. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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.
Purity & Documentation
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Data Sheet (279 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
[1]. Kang CH, et al. Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC). Biochem Biophys Res Commun. 2018 Oct 28;505(2):542-547. [Content Brief]
[2]. Chen X, et al. Mighty mini-PROTACs: an emerging class of degraders. Eur J Med Chem. 2026 Jan 5;301:118202. [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 (sealed storage, away from moisture). 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 | 0.9218 mL | 4.6092 mL | 9.2185 mL | 23.0461 mL |
| 5 mM | 0.1844 mL | 0.9218 mL | 1.8437 mL | 4.6092 mL | |
| 10 mM | 0.0922 mL | 0.4609 mL | 0.9218 mL | 2.3046 mL | |
| 15 mM | 0.0615 mL | 0.3073 mL | 0.6146 mL | 1.5364 mL | |
| 20 mM | 0.0461 mL | 0.2305 mL | 0.4609 mL | 1.1523 mL | |
| 25 mM | 0.0369 mL | 0.1844 mL | 0.3687 mL | 0.9218 mL | |
| 30 mM | 0.0307 mL | 0.1536 mL | 0.3073 mL | 0.7682 mL | |
| 40 mM | 0.0230 mL | 0.1152 mL | 0.2305 mL | 0.5762 mL | |
| 50 mM | 0.0184 mL | 0.0922 mL | 0.1844 mL | 0.4609 mL | |
| 60 mM | 0.0154 mL | 0.0768 mL | 0.1536 mL | 0.3841 mL | |
| 80 mM | 0.0115 mL | 0.0576 mL | 0.1152 mL | 0.2881 mL |
TD-004 Related Classifications
HY-180970 Related Classifications
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