Eftozanermin alfa  (Synonyms: ABBV-621)

Eftozanermin alfa (ABBV-621) is a tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R) agonist. Eftozanermin alfa is a fusion protein consisting of a mutant immunoglobulin G1-Fc linked to 2 single-chain trimers of TRAIL. Eftozanermin alfa induces apoptosis in tumor cells by activation of death receptors (DR4 receptor and DR5 receptor) with K_ds of 780 nM and 635 nM. Eftozanermin alfa can be used for the research of multiple solid and heme malignancies^[1][2][3].

Eftozanermin alfa demonstrates a highly significant synergistic effect when combined with Venetoclax (HY-15531) in acute ​myeloid ​leukemia cell lines and proteasome inhibitors (Bortezomib (HY-10227) or Carfilzomib (HY-10455))^[1][2].
Eftozanermin alfa (0-1 nM, 24 h) has a killing effect on 36% (45/126) of human solid tumor cells through the apoptosis pathway (increase in caspase-3/7/8 activity)^[1][3].

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

Eftozanermin alfa (1 mg/kg, i.p., every other day for 5 days) induces robust single-agent antitumor activity with complete regression of SKM-1 tumors in mice^[1].
Eftozanermin alfa (5 mg/kg, i.p., every other day for 5 days) demonstrates significant and broad anti-tumor activity in patient-derived xenograft (PDX) mice models^[3].
Eftozanermin alfa (0.3-30 mg/kg, i.p., every other day for 5 days) exhibits clear dose-dependent anti-tumor activity against colorectal and breast cancer in mice^[3].
Eftozanermin alfa (3-15 mg/kg, i.p., once every two days or 2-5 times a week) demonstrates significantly superior antitumor efficacy when combined with either Irinotecan (HY-16562), Docetaxel (HY-B0011), A-1331852 (HY-19741) compared to any single agent alone in mice^[3].
Eftozanermin alfa (4-100 mg/kg, i.v., once weekly for 5 weeks) exhibits favorable pharmacokinetic profile and a wide therapeutic window in cynomolgus monkey^[3].

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

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

167.52 kDa

1820660-69-2

Liquid

Colorless to light yellow

[Eftozanermin alfa]

Shipping with dry ice.

Please store the product under the recommended conditions in the Certificate of Analysis.

• 
  [Homo sapiens TNFSF10 (TNF superfamily member 10, tumor necrosis factor (ligand)superfamily, member 10)]2-Homo sapiens IGHG1 Fc (Fragment constant)

• 
  Immobilized Human DR5/TRAIL R2 Protein (His Tag) can bind Eftozanermin alfa. The EC₅₀ for this effect is 4.94 ng/mL.

• [1]. Tahir SK, et al. Activity of eftozanermin alfa plus venetoclax in preclinical models and patients with acute myeloid leukemia. Blood. 2023 Jan 30:blood.2022017333.  [Content Brief]

  [2]. Silva A S, et al. Ex Vivo Drug Sensitivity and Functional Genomics Platform Identifies Novel Combinations Targeting Intrinsic and Extrinsic Apoptotic Signaling Pathways in Multiple Myeloma. Blood, 2020, 136(Supplement 1):49-50.

  [3]. Phillips DC, et al. Hexavalent TRAIL Fusion Protein Eftozanermin Alfa Optimally Clusters Apoptosis-Inducing TRAIL Receptors to Induce On-Target Antitumor Activity in Solid Tumors. Cancer Res. 2021 Jun 15;81(12):3402-3414.  [Content Brief]