| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Trabedersen specifically targets the messenger RNA (mRNA) of TGF-beta2. It is a complementary antisense strand that hybridizes to the TGF-beta2 mRNA, leading to its degradation via RNase H and blocking the translation of the protein. This mechanism prevents the synthesis of the immunosuppressive and pro-tumorigenic TGF-beta2 protein.
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| ln Vitro |
In the human pancreatic cancer cell line Hup-T3, Trabedersen (1-80 μM; 7 days) decreases TGF-β2 secretion with an IC50 in the low μM range, evidently suppresses cell proliferation, and totally prevents pancreatic cancer cell migration[2]. Pancreatic cancer cells' TGF-β2-mediated immunosuppression is reversed by trametersen[2].
In vitro, Trabedersen specifically binds to TGF-beta2 mRNA, causing its degradation and preventing TGF-beta2 protein synthesis. By lowering the levels of TGF-beta2 in the tumor microenvironment, it is expected to reverse immunosuppression and inhibit the proliferation and invasion of cancer cells. |
| ln Vivo |
In an orthotopic mouse model of metastatic pancreatic cancer, Trabedersen treatment (initial loading dose of 50 mg/kg bodyweight followed by 16 mg/kg three times a week; ip) dramatically lowers tumor development, lymph node metastasis, and angiogenesis[2].
Trabedersen has been studied in vivo for the treatment of malignant brain tumors, such as anaplastic astrocytoma and glioblastoma, as well as other TGF-beta2-overexpressing solid tumors of the skin, pancreas, and colon. By inhibiting TGF-beta2, it can restore anti-tumor immunity and suppress tumor growth. |
| Enzyme Assay |
A cell-free RNase H assay is performed to confirm the antisense mechanism. Trabedersen is hybridized to its target TGF-beta2 RNA strand. Recombinant RNase H is added to the reaction. The degradation of the RNA strand is monitored by gel electrophoresis or by using a fluorescence-based assay to confirm that the compound is capable of eliciting the desired cleavage.
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: Hup-T3 cells Tested Concentrations: 1 μM, 2.5 μM, 5 μM, 10 μM, 20 μM, 40 μM, 60 μM, 80 μM Incubation Duration: 7 days Experimental Results: Inhibited cell proliferation, and completely blocked migration of pancreatic cancer cells. Cellular assays for Trabedersen are conducted in cancer cell lines that overexpress TGF-beta2 (e.g., pancreatic or glioma cells). Cells are treated with Trabedersen via transfection or with a delivery vehicle. After 24-72 hours, the cells are harvested. TGF-beta2 protein levels in the lysate and supernatant are measured by ELISA to confirm target knockdown. Cell proliferation and apoptosis are also assessed. |
| Animal Protocol |
Animal/Disease Models: Eightweeks old male athymic nude mice (BALB⁄Cnu ⁄nu) bearing human pancreatic cancer cells[2].
Doses: Initial loading dose of 50 mg/kg bodyweight followed by 16 mg/kg three times a week. Route of Administration: intraperitoneal (ip) injection; three times a week; for 27 days Experimental Results: Dramatically decreased tumor growth, lymph node metastasis and angiogenesis. In vivo studies are conducted in immunocompetent mice bearing syngeneic tumors or in human xenograft models. Trabedersen is administered by intratumoral or systemic injection. Tumor growth is measured. To assess immune modulation, tumor-infiltrating lymphocytes are analyzed by flow cytometry, and systemic cytokine levels (e.g., TGF-beta2) are measured in the serum by ELISA. |
| ADME/Pharmacokinetics |
Trabedersen‘s pharmacokinetic profile is characteristic of an antisense oligonucleotide. It is typically administered via local injection (e.g., intratumorally or intrathecally) to reach the target site. It has a relatively short half-life in circulation and is taken up by tissues where it exerts its prolonged pharmacodynamic effect.
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| Toxicity/Toxicokinetics |
Toxicological profiles from clinical and preclinical studies show that Trabedersen is generally well-tolerated. The most common adverse events are related to the local administration route and mild, transient flulike symptoms. No significant systemic toxicities have been reported, and its specificity for TGF-beta2 minimizes off-target effects.
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| References |
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| Additional Infomation |
Trabedersen is a transforming growth factor (TGF)-β2-specific antisense oligodeoxynucleotide with the sequence 5'-CGGCATGTCTATTTTGTA-3', possessing potential antitumor activity. Trabedersen binds to TGF-β2 mRNA, inhibiting protein translation and thus reducing TGF-β2 protein levels; reduced intratumoral TGF-β2 levels may lead to inhibition of tumor cell growth, migration, and angiogenesis. TGF-β2 is a cytokine frequently overexpressed in various malignancies and may play an important role in promoting tumor cell growth, progression, and migration.
Drug Indications Investigations have been conducted in the treatment of brain cancer, colorectal cancer, melanoma, and pancreatic cancer. Mechanism of Action AP 12009 is an antisense oligodeoxynucleotide that specifically inhibits TGF-β2. TGF-β overexpression is a hallmark of various malignancies. This is because TGF-β plays a key role in regulating key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. Trabedersen (AP 12009) has advanced into clinical development, showing promising results in Phase II studies for patients with high-grade gliomas. It received orphan drug status in the EU and the US for the treatment of pancreatic cancer, glioblastoma, and other tumors. It is a valuable tool for validating TGF-beta2 as a therapeutic target in immuno-oncology. |
| Molecular Formula |
C177H226N60O94P17S17
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|---|---|
| Molecular Weight |
5769.6928858757
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| Exact Mass |
5766.557
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| CAS # |
925681-61-4
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| PubChem CID |
170458200
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
42
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| Hydrogen Bond Acceptor Count |
131
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| Rotatable Bond Count |
102
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| Heavy Atom Count |
365
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| Complexity |
15200
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S=P(O)(OCC1C(CC(N2C=NC3C(NC(N)=NC2=3)=O)O1)OP(O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OCC1C(CC(N2C(N=C(C=C2)N)=O)O1)OP(O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OCC1C(CC(N2C=NC3C(N)=NC=NC2=3)O1)OP(O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)OP(=O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)O)S)=S)=S)=S)=S)=S)=S)OC1CC(N2C(NC(C(C)=C2)=O)=O)OC1COP(O)(OC1CC(N2C=NC3C(N)=NC=NC2=3)OC1COP(O)(OC1CC(N2C(N=C(C=C2)N)=O)OC1COP(O)(OC1CC(N2C=NC3C(NC(N)=NC2=3)=O)OC1COP(O)(OC1CC(N2C=NC3C(NC(N)=NC2=3)=O)OC1COP(O)(OC1CC(N2C(N=C(C=C2)N)=O)OC1CO)=S)=S)=S)=S)=S.S=P(O)(OCC1C(CC(N2C(NC(C(C)=C2)=O)=O)O1)OP(O)(OCC1C(CC(N2C=NC3C(N)=NC=NC2=3)O1)O)=S)OC1CC(N2C=NC3C(NC(N)=NC2=3)=O)OC1COP(O)(OC1CC(N2C(NC(C(C)=C2)=O)=O)OC1CO[P+](=O)S)=S
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| InChi Key |
HSWLVDBGZCETRH-UHFFFAOYSA-O
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| InChi Code |
InChI=1S/C137H175N46O73P13S13.C40H50N14O21P4S4/c1-54-27-173(132(198)164-117(54)186)91-13-60(185)75(231-91)34-217-257(204,270)247-64-17-95(174-28-55(2)118(187)165-133(174)199)234-78(64)37-222-262(209,275)249-66-19-97(176-30-57(4)120(189)167-135(176)201)236-80(66)39-223-267(214,280)253-70-23-101(180-50-151-106-111(142)147-48-149-113(106)180)240-84(70)43-227-263(210,276)250-67-20-98(177-31-58(5)121(190)168-136(177)202)235-79(67)38-221-259(206,272)245-62-15-93(171-11-8-89(139)156-130(171)196)232-76(62)35-219-261(208,274)248-65-18-96(175-29-56(3)119(188)166-134(175)200)238-82(65)41-225-268(215,281)255-73-26-104(183-53-154-109-116(183)160-128(145)163-125(109)194)242-86(73)45-228-264(211,277)251-68-21-99(178-32-59(6)122(191)169-137(178)203)237-81(68)40-224-266(213,279)252-69-22-100(179-49-150-105-110(141)146-47-148-112(105)179)239-83(69)42-226-260(207,273)246-63-16-94(172-12-9-90(140)157-131(172)197)233-77(63)36-220-265(212,278)254-72-25-103(182-52-153-108-115(182)159-127(144)162-124(108)193)243-87(72)46-229-269(216,282)256-71-24-102(181-51-152-107-114(181)158-126(143)161-123(107)192)241-85(71)44-218-258(205,271)244-61-14-92(230-74(61)33-184)170-10-7-88(138)155-129(170)195;1-16-7-51(39(59)49-35(16)56)27-4-19(23(70-27)9-65-76(61)80)73-78(63,82)68-12-25-21(6-29(72-25)54-15-46-31-34(54)47-38(42)48-37(31)58)75-79(64,83)67-11-24-20(5-28(71-24)52-8-17(2)36(57)50-40(52)60)74-77(62,81)66-10-22-18(55)3-26(69-22)53-14-45-30-32(41)43-13-44-33(30)53/h7-12,27-32,47-53,60-87,91-104,184-185H,13-26,33-46H2,1-6H3,(H,204,270)(H,205,271)(H,206,272)(H,207,273)(H,208,274)(H,209,275)(H,210,276)(H,211,277)(H,212,278)(H,213,279)(H,214,280)(H,215,281)(H,216,282)(H2,138,155,195)(H2,139,156,196)(H2,140,157,197)(H2,141,146,148)(H2,142,147,149)(H,164,186,198)(H,165,187,199)(H,166,188,200)(H,167,189,201)(H,168,190,202)(H,169,191,203)(H3,143,158,161,192)(H3,144,159,162,193)(H3,145,160,163,194);7-8,13-15,18-29,55H,3-6,9-12H2,1-2H3,(H10-,41,42,43,44,47,48,49,50,56,57,58,59,60,61,62,63,64,80,81,82,83)/p+1
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| Chemical Name |
1-[5-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[2-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[5-(4-amino-2-oxopyrimidin-1-yl)-2-(hydroxymethyl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione;[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-oxo-sulfanylphosphanium
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O: 100 mg/mL (17.33 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1733 mL | 0.8666 mL | 1.7332 mL | |
| 5 mM | 0.0347 mL | 0.1733 mL | 0.3466 mL | |
| 10 mM | 0.0173 mL | 0.0867 mL | 0.1733 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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