2. PROTAC Protein Tyrosine Kinase/RTK
  3. PROTACs Anaplastic lymphoma kinase (ALK)
  4. 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).

For research use only. We do not sell to patients.

TD-004

TD-004 Chemical Structure

CAS No. : 2162120-55-8

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TD-004 Related Antibodies

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von Hippel-Lindau (VHL) Cereblon MDM2 cIAP1

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Description

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[1][2]. (Pink: Anaplastic lymphoma kinase (ALK) ligand (HY-15656); Blue: VHL ligand (HY-125845); Black: linker).

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.

TD-004 Related Antibodies

Western Blot Analysis[1]

Cell Line: NCI-H3122 cell
Concentration: 0.03, 0.3, 3 and 30 μM
Incubation Time: 8 or 16 h
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.

Western Blot Analysis[1]

Cell Line: H3122 cells
Concentration: 0.3 and 3 μM
Incubation Time: 1 h
Result: Induced ALK degradation, which was blocked by co-treatment with Epoxomicin (HY-13821) (1 μM).

Western Blot Analysis[1]

Cell Line: SU-DHL-1 cells
Concentration: 0.2 μM
Incubation Time: 16 h
Result: Mediated degradation of the NPM-ALK protein, which was inhibited by the VHL ligand.
In Vivo

TD-004 (58 mg/kg, i.p., once daily for 14 days) effectively suppresses growth of tumor harboring fusion ALK protein in H3122 xenograft mice model[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: H3122 cells (ALK-positive cells) (5 x 10 6) induced-female BALB/c nude mice[1].
Dosage: 58 mg/kg
Administration: i.p., once daily for 14 days
Result: Reduced tumor volume.
Did Not affect body weight.
Molecular Weight

1084.78

Formula

C55H70ClN9O8S2
CAS No.
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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Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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TD-004 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

TD-0042162120-55-8TD004TD 004PROTACsAnaplastic lymphoma kinase (ALK)Anaplastic lymphoma kinaseALK tyrosine kinase receptorCD246Cluster of differentiation 246SU-DHL-1 cellsH3122 cellsanaplastic large cell lymphoma and non-small cell lung cancerInhibitorinhibitorinhibit

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