ETN029  (Synonyms: MC339)

ETN029 (MC339) is a selective DLL3 ligand. ETN029 labeled with ²²⁵Ac has dose-dependent cytotoxicity in SCLC, NEPC and metastatic melanoma cells and increases the phosphorylation of H2AX expression. ETN029 labeled with 177Lu shows rapid uptake persistent tumor retention and favorable tumor-to-kidney ratio. ETN029 can be used for cancers like SCLC and NEPC imaging and research^[1][2].

ETN029 (MC339) binds human DLL3 with picomolar affinity and specificity, showing high cell binding and internalization in both SHP-77 and transgenic CT26.DLL3 cell lines, with minimal binding to DLL3-negative CT26.WT controls^[3].
[²²⁵Ac]Ac-ETN029 exhibits dose-dependent cytotoxicity in SCLC, NEPC, and metastatic melanoma cell lines and increases the phosphorylation of H2AX, a marker for DNA double-strand breaks^[3].

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

A biodistribution study of [¹⁷⁷Lu]Lu-ETN029 (MC339) in a SHP-77 cell-derived xenograft (CDX) mouse model showed that radionuclide distribution occurred primarily to the tumor with rapid uptake and persistent tumor retention throughout the study. Among normal tissues, the kidneys showed the highest uptake, suggesting renal excretion as the major elimination pathway^[3].
In CDX models (NCI-H69, SHP-77), a single dose of [²²⁵Ac]Ac-ETN029 (0.35-1.4 µCi) resulted in robust tumor regression and prolonged survival^[3].

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

2142.45

C₁₀₁H₁₄₀N₂₂O₂₆S₂

3066864-32-9

Solid

White to light yellow

CC(N[C@@H](CC1=CNC2=C1C=CC=C2)C(N[C@H](C(N([C@H](C(N[C@@H]3C(N[C@@H](CC4CCN(CC(O)=O)CC4)C(N[C@@H](CC(N)=O)C(N[C@@H](CC5=CC=C6C=CC=CC6=C5)C(N[C@@H](CCCCNC(CN7CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC7)=O)C(N[C@@H](CC(O)=O)C(N[C@H](C(N[C@H](C(N8CCC[C@H]8C(N)=O)=O)CC9=CNC%10=C9C=CC=C%10)=O)CSCSC3)=O)=O)=O)=O)=O)=O)=O)CC(C)(C)C)C)=O)[C@@H](C)O)=O)=O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

* 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 and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. A. Savinainen, et al. 1153P Preclinical characterization of MC339: A novel radiotherapeutic agent for DLL3 expressing cancers. Neuroendocrine tumours Volume 35, Supplement 2 S755 September 2024.

  [2]. Ninatti G, et al. Radioligand Therapy in Cancer Management: A Global Perspective. Cancers (Basel). 2025;17(21):3412. Published 2025 Oct 23.  [Content Brief]

  [3]. Ku SY, et al. Preclinical Activity of the DLL3-Targeted T-cell Engager MK-6070 in Neuroendocrine Prostate Cancer. Mol Cancer Ther. 2026;25(2):346-354.  [Content Brief]