Trabedersen  (Synonyms: AP 12009)

Trabedersen (AP 12009) is an orally active synthetic antisense phosphorothioate oligodeoxynucleotide that selectively targets human TGFβ2 mRNA. Trabedersen blocks TGFβ2 protein production, enters the nucleus without a transfection vector, and exerts dose-dependent antitumor effects. By reversing TGFβ2-induced immunosuppression and enhancing immune cytotoxicity, Trabedersen exhibits significant antiproliferative, antimigratory, and antimetastatic activities, with favorable safety profiles. Trabedersen is widely used in research related to various solid tumors, including anaplastic astrocytoma, glioblastoma, colorectal tumor, and melanoma^[1][2][3][4].

Trabedersen (1, 5, 10 μM) reduces TGFβ2 secretion by 49-73% and cell proliferation by 24-41%, inhibits migration, and enhances LAK cell-mediated cytotoxicity in human high-grade astrocytoma (III/IV) cells^[1].
Trabedersen inhibits TGFβ2 secretion by 43%, reduces cell proliferation by up to 77%, blocks migration, and increases LAK cell cytotoxicity 4-fold in human pancreatic cancer cell lines (Hup-T3, PA-TU 8902)^[1].
Trabedersen (1-80 μM; 7 days) potently suppresses TGF-β2 secretion from human pancreatic cancer Hup-T3 cells, with an IC₅₀ of 1.7 μM and complete inhibition at concentrations ≥60 μM after 7 days of treatment^[3].
Trabedersen (2.5-80 μM; 7 days) strongly inhibits proliferation of human pancreatic cancer Hup-T3 cells, with an IC₅₀ of 4.6 μM and >90% inhibition at 40 μM after 7 days of treatment^[3].
Trabedersen (5 μM; up to 7 days) completely inhibits migration of human pancreatic cancer PA-TU-8902 cells in a spheroid model when treated with 5 μM for up to 7 days^[3].
Trabedersen (200 nM, 5 μM; 6 h, variable) efficiently reverses TGF-β2-mediated immunosuppression of human pancreatic cancer Hup-T3 cells, resulting in significantly increased LAK cell-mediated cytotoxicity against Hup-T3 target cells^[3].
Trabedersen (10-80 μM) potently inhibits TGF-β2 secretion in human glioblastoma multiforme cells, with 10 μM trabedersen acting to a greater extent than 80 μM trabedersen^[4].

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

Trabedersen (1.4-50 nmol; intrathecal administration; single bolus dose; 5 nmol/h; intracerebral administration; continuous infusion; 1 week) is well tolerated in rabbits and cynomolgus monkeys at single intrathecal bolus doses up to 50 nmol, whereas continuous intracerebral infusion at a rate of 5 nmol/h for 1 week induces mild to moderate local leukocyte infiltration in rabbits^[1].
Trabedersen (30-1000 mg/kg; intravenous injection; single bolus dose) is well tolerated in mice and rats at single intravenous bolus doses up to 100 mg/kg, with an LD₅₀ value of 706 mg/kg in mice and 1175 mg/kg in rats^[1].
Continuous intravenous infusion of Trabedersen at a dose of 1 mg/kg/day is well tolerated in rats and monkeys, whereas continuous infusion at higher doses induces reversible inflammation and tissue damage; intravenous infusion at a dose of 8 mg/kg every other day for 4 weeks is also well tolerated in monkeys^[1].
In cynomolgus monkeys, trabedersen sodium (5-160 mg/kg; intravenous infusion; 2 h duration; single dose) is well tolerated at intravenous doses up to 20 mg/kg over a 2-hour infusion with respect to cardiovascular and complement activation endpoints; it is well tolerated at doses below 5 mg/kg with respect to hematological indices^[1].
Trabedersen (0.25-50 mg/kg; i.p.; three times per week; approximately 32-35 days) sodium exhibits potent dose-dependent antitumor activity in orthotopic xenograft melanoma mouse models, reduces lung metastasis, and shows evidence of immunomodulatory effects as well as cellular/nuclear uptake; among these, the 50/16 mg/kg dosing regimen significantly reduces the average tumor weight to 0.395 g^[2].
Trabedersen significantly reduces the tumor weight, tumor cell proliferation level, tumor vascularization degree, and incidence of lymph node metastasis of primary pancreatic cancer in orthotopic xenograft mouse models^[3].

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

5768.70

925681-61-4

Solid

White to off-white

DNA, d(P-thio)(C-G-G-C-A-T-G-T-C-T-A-T-T-T-T-G-T-A)

[Trabedersen]

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

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

* 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.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Vallières L. Trabedersen, a TGFbeta2-specific antisense oligonucleotide for the treatment of malignant gliomas and other tumors overexpressing TGFbeta2[J]. IDrugs, 2009, 12(7): 445-453.

  [2]. Rothhammer-Hampl T, et al. Targeted suppression of TGF-beta2 by trabedersen (AP 12009) in an orthotopic xenograft melanoma mouse model[J]. Cancer Research, 2012, 72(8_Supplement): 2362-2362.

  [3]. Schlingensiepen KH, et al. Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. Cancer Sci. 2011;102(6):1193-1200.  [Content Brief]

  [4]. Bogdahn U, et al. Targeted therapy for high-grade glioma with the TGF-β2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro Oncol. 2011;13(1):132-142.