 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C177H226N60O94P17S17 |
| Molecular Weight | 5769.6928858757 |
| Exact Mass | 5766.557 |
| CAS # | 925681-61-4 |
| PubChem CID | 170458200 |
| Appearance | White to off-white solid powder |
| Hydrogen Bond Donor Count | 42 |
| Hydrogen Bond Acceptor Count | 131 |
| Rotatable Bond Count | 102 |
| Heavy Atom Count | 365 |
| Complexity | 15200 |
| Defined Atom Stereocenter Count | 0 |
| 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 |
| InChi Key | HSWLVDBGZCETRH-UHFFFAOYSA-O |
| 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 |
| 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 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| 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. |
| 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. |
| References |
[1]. Luc Vallières. Trabedersen, a TGFbeta2-specific antisense oligonucleotide for the treatment of malignant gliomas and other tumors overexpressing TGFbeta2. IDrugs. 2009 Jul;12(7):445-53. [2]. Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. Cancer Sci. 2011 Jun;102(6):1193-200. |
| Additional Infomation |
Trabedersen is a transforming growth factor (TGF)-beta2 specific phosphorothioate antisense oligodeoxynucleotide with the sequence 5'-CGGCATGTCTATTTTGTA-3', with potential antineoplastic activity. Trebedersen binds to TGF-beta2 mRNA causing inhibition of protein translation, thereby decreasing TGF-beta2 protein levels; decreasing intratumoral TGF-beta2 levels may result in the inhibition of tumor cell growth and migration, and tumor angiogenesis. TGF-beta2, a cytokine often over-expressed in various malignancies, may play an important role in promoting the growth, progression, and migration of tumor cells. Drug Indication Investigated for use/treatment in brain cancer, colorectal cancer, melanoma, and pancreatic cancer. Mechanism of Action AP 12009 is an antisense oligodeoxynucleotide that specifically inhibits TGF-beta2. TGF-beta overexpression is a hallmark of various malignant tumors. This is due to the pivotal role of TGF-beta as it regulates key mechanisms of tumor development, namely immunosuppression, metastasis, angiogenesis, and proliferation. |
Solubility Data
| Solubility (In Vitro) | H2O: 100 mg/mL (17.33 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |