ABT-510 TFA is a synthetic peptide made up of nine amino acids that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1), a TSP-1 mimetic drug. It is available as the trifluoroacetic acid (TFA) salt form of ABT-510. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin 8 (IL-8) are inhibited by ABT-510. These pro-angiogenic growth factors are crucial for tumor neovascularization. In a phase 1 clinical trial with newly diagnosed glioblastoma, the TSR-based drug ABT-510 demonstrated anti-angiogenic properties.
Physicochemical Properties
| Molecular Formula | C46H83N13O11.C2HF3O2 |
| Molecular Weight | 1108.253 |
| Exact Mass | 993.634 |
| CAS # | 251579-55-2 |
| Related CAS # | ABT-510 acetate;442526-87-6 |
| PubChem CID | 6918562 |
| Sequence | GGVXTXIRP |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2.065 |
| Hydrogen Bond Donor Count | 11 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 30 |
| Heavy Atom Count | 70 |
| Complexity | 1830 |
| Defined Atom Stereocenter Count | 10 |
| SMILES | CCC[C@H](NC([C@@H](NC(C(NC([C@@H](NC(CNC(CN(C(C)=O)C)=O)=O)C(C)C)=O)[C@H](CC)C)=O)[C@H](O)C)=O)C(N[C@H](C(N[C@H](C(N1CCC[C@H]1C(NCC)=O)=O)CCCNC(N)=N)=O)[C@H](CC)C)=O |
| InChi Key | RIWLPSIAFBLILR-WVNGMBSFSA-N |
| InChi Code | InChI=1S/C46H83N13O11/c1-12-18-30(39(64)55-36(26(7)13-2)42(67)53-31(19-16-21-50-46(47)48)45(70)59-22-17-20-32(59)40(65)49-15-4)52-44(69)38(28(9)60)57-43(68)37(27(8)14-3)56-41(66)35(25(5)6)54-33(62)23-51-34(63)24-58(11)29(10)61/h25-28,30-32,35-38,60H,12-24H2,1-11H3,(H,49,65)(H,51,63)(H,52,69)(H,53,67)(H,54,62)(H,55,64)(H,56,66)(H,57,68)(H4,47,48,50)/t26-,27-,28+,30-,31-,32-,35-,36-,37+,38-/m0/s1 |
| Chemical Name | (2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2R,3S)-2-[[(2S)-2-[[2-[[2-[acetyl(methyl)amino]acetyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]pentanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-N-ethylpyrrolidine-2-carboxamide |
| Synonyms | ABT 510; ABT510; ABT-510 |
| 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 |
| 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 epithelial cancer cell lines SKOV3, OVCAR3, and CAOV3, ABT-510 (1, 5, 10, 20, and 50 nM; 24 hours) induces ID 8 cell carcinoma and (50 nM, 24 hours) increases the incidence of liver cancer [ABT-510 (0-10 μM; 7 days) inhibits the growth and height of NO-stimulated vascular cells into the extracellular matrix]. ABT-510 has the ability to suppress both NO-driven cGMP background and tumor-driven vascular cell proliferation [3]. |
| ln Vivo | ABT-510 (100 mg/kg; intraperitoneal injection; once daily for 90 days) dramatically decreases the size, volume, and spread of secondary tumors in mice as well as cellular luminescence in vivo [1]. In models of inflammatory bowel illness, -510 (60 mg/kg; subcutaneous minipump; once daily for 7 days) decreases angiogenesis and inflammation [2]. |
| Cell Assay |
Apoptosis analysis [1] Cell Types: ID8, SKOV3, OVCAR3 and CAOV3 cells Tested Concentrations: 1, 5, 10, 20, 50nM Incubation Duration: 24 hrs (hours) Experimental Results: Induced cells in ID8 human EOC cell lines SKOV3, OVCAR3 and CAOV3 Increased apoptosis. Apoptosis analysis[3] Cell Types: Tissue biopsy of B16F10 melanoma tumors grown in C57BL/6 mice Tested Concentrations: 0-10 μM Incubation Duration: 7 days Experimental Results: Inhibition of NO-stimulated vascular cell growth into the extracellular matrix and Invasion. |
| Animal Protocol |
Animal/Disease Models: TSP-1-Null mice (C57BL/6 background; orthotopic, syngeneic model of epithelial ovarian cancer) [1]. Doses: 100 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 90 days Experimental Results: diminished ovarian tumor growth in wild-type and TSP-1 null mice. The amount of ascites is Dramatically diminished and the formation of peritoneal lesions is completely eliminated. Reversal of ovarian tumor hypervascularization and increased proportion of mature vessels. Animal/Disease Models: TSP-1-Null mice (C57BL/6 background; 6 weeks old; DSS-induced inflammatory bowel disease mouse model) [2]. Doses: 60 mg/kg Route of Administration: subcutaneously (sc) (sc) implanted osmotic minipump (0.5 μL/h); one time/day for 7 days Experimental Results: Dramatically delayed DSS-induced bleeding and improved overall disease severity. Inflammation grade and angiogenesis were Dramatically diminished |
| References |
[1]. ABT-510 induces tumor cell apoptosis and inhibits ovarian tumor growth in an orthotopic, syngeneic model of epithelial ovarian cancer. Mol Cancer Ther. 2009 Jan;8(1):64-74. [2]. Thrombospondin 1 and its mimetic peptide ABT-510 decrease angiogenesis and inflammation in a murine model of inflammatory bowel disease. Pathobiology. 2008;75(1):9-21. [3]. Isenberg JS, et.al. Differential effects of ABT-510 and a CD36-binding peptide derived from the type 1 repeats of thrombospondin-1 on fatty acid uptake, nitric oxide signaling, and caspase activation in vascular cells. Biochem Pharmacol. 2008 Feb 15;75(4):875-82. |
| Additional Infomation |
ABT-510 is a peptide mimetic of thrombospondin-1 (TSP-1), blocks angiogenesis in vitro and in vivo, and slows tumor growth. It is developed by Abbott Laboratories for the treatment of Solid Tumors, Lymphoma and Melanoma. TSP-1 Mimetic ABT-510 is a synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8). (NCI04) Drug Indication Investigated for use/treatment in lymphoma (unspecified), melanoma, and solid tumors. Mechanism of Action ABT-510 is a synthetic peptide that mimics the anti-angiogenic activity of the naturally occurring protein, thrombospondin-1 (TSP-1). Angiogenesis is the process of new blood vessel formation. ABT-510 blocks the actions of multiple pro-angiogenic growth factors known to play a role in cancer related blood vessel growth, such as VEGF, bFGF, HGF, and IL-8. ABT-510 is the first compound with this mechanism of action to be studied. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 | 0.9023 mL | 4.5116 mL | 9.0232 mL | |
| 5 mM | 0.1805 mL | 0.9023 mL | 1.8046 mL | |
| 10 mM | 0.0902 mL | 0.4512 mL | 0.9023 mL |