TD-004
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).
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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。
- CAS 番号: 2162120-55-8
- 分子式: C55H70ClN9O8S2
- 分子量:1084.78
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
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生物活性
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VHL |
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.
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.
化学情報
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CAS 番号 2162120-55-8
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分子量 1084.78
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分子式 C55H70ClN9O8S2
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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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[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]
Calculators
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