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ATN-161 is a novel and potent small peptide inhibitor of the integrin α5β1, it inhibits the angiogenesis and growth of liver metastases in a murine model. ATN-161 interacts with the N-terminus of the β1-domain of integrin α5β1, which may lock this integrin in an inactive conformation. Integrin α5β1 is expressed on activated endothelial cells and plays a critical role in tumor angiogenesis. Therefore, ATN-161 has potential anticancer activities.The combination of ATN-161 with 5-fluorouracil (5-FU) chemotherapy has shown enhanced antineoplastic effect.
Physicochemical Properties
| Molecular Formula | C23H35N9O8S | |
| Molecular Weight | 597.64 | |
| Exact Mass | 597.232 | |
| CAS # | 262438-43-7 | |
| Related CAS # | ATN-161 trifluoroacetate salt;904763-27-5 | |
| PubChem CID | 9960285 | |
| Appearance | Typically exists as solid at room temperature | |
| Density | 1.4±0.1 g/cm3 | |
| Boiling Point | 1297.2±65.0 °C at 760 mmHg | |
| Flash Point | 738.3±34.3 °C | |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C | |
| Index of Refraction | 1.612 | |
| LogP | -3.52 | |
| Hydrogen Bond Donor Count | 9 | |
| Hydrogen Bond Acceptor Count | 10 | |
| Rotatable Bond Count | 15 | |
| Heavy Atom Count | 41 | |
| Complexity | 1020 | |
| Defined Atom Stereocenter Count | 5 | |
| SMILES | S([H])C([H])([H])[C@@]([H])(C(N([H])[C@]([H])(C(N([H])[H])=O)C([H])([H])C(N([H])[H])=O)=O)N([H])C([C@]([H])(C([H])([H])O[H])N([H])C([C@]([H])(C([H])([H])C1=C([H])N=C([H])N1[H])N([H])C([C@]1([H])C([H])([H])C([H])([H])C([H])([H])N1C(C([H])([H])[H])=O)=O)=O)=O |
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| InChi Key | MMHDBUJXLOFTLC-WOYTXXSLSA-N | |
| InChi Code | InChI=1S/C23H35N9O8S/c1-11(34)32-4-2-3-17(32)23(40)29-14(5-12-7-26-10-27-12)20(37)30-15(8-33)21(38)31-16(9-41)22(39)28-13(19(25)36)6-18(24)35/h7,10,13-17,33,41H,2-6,8-9H2,1H3,(H2,24,35)(H2,25,36)(H,26,27)(H,28,39)(H,29,40)(H,30,37)(H,31,38)/t13-,14-,15-,16-,17-/m0/s1 | |
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| 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 |
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| 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 | When compared to control and single-agent therapy, the combination of ATN-161 plus 5-FU significantly reduces tumor cell proliferation (p<0.01). Furthermore, apoptotic (TUNEL-positive) tumor cells are significantly increased by combination therapy (p <0.03), while no increase in TUNEL-positive tumor cells is observed with single-agent therapy. After 48 hours of incubation, ATN-161 treatment significantly lowers the EC number (21% decrease) in comparison to the control group (p<0.03) [1]. ATN-161 did not stop proliferation in hCECs, but it did prevent VEGF-induced migration and capillary tube formation. Starting at 100 nM (P <0.001 vs. VEGF group), ATN-161 reduces the number of cells migrating in response to VEGF in a dose-dependent manner[2]. | ||
| ln Vivo | Preliminary studies using human colon cancer xenografts (HT29) lacking α5β1 demonstrate that ATN-161 treatment dramatically lowers tumor weight and vessel density[1]. Following laser photocoagulation, injection of ATN-161 inhibits choroidal neovascularization (CNV) leakage and neovascularization to a degree comparable to that of AF564[2]. | ||
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| References |
[1]. Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int J Cancer. 2003 Apr 20;104(4):496-503. [2]. The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro and in vivo. Invest Ophthalmol Vis Sci. 2011 Sep 14;52(10):7213-20. |
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| Additional Infomation |
ATN-161 is a non-RGD based integrin binding peptide targeting alpha-5 beta-1 and alpha-v beta-3. It inhibits the migration and adhesion of particular integrins on activated endothelial cells that play a critical role in tumor angiogenesis. This approach targeting both the tumor vasculature and the cancer cells themselves, may be effective in single therapy as well as combination therapy. Since the expression of alpha(5)beta(1) integrin by cancer cells and the role of this molecule in tumor angiogenesis is similar across a range of different cancers, the therapeutic benefit of ATN-161 is expected to extend to a variety of cancers. Alpha V Beta 1 Inhibitor ATN-161 is a small peptide antagonist of integrin alpha5beta1 with potential antineoplastic activity. ATN-161 selectively binds to and blocks the receptor for integrin alpha5beta1, thereby preventing integrin alpha5beta1 binding. This receptor blockade may result in inhibition of endothelial cell-cell interactions, endothelial cell-matrix interactions, angiogenesis, and tumor progression. Integrin alpha5beta1 is expressed on endothelial cells and plays a crucial role in endothelial cell adhesion and migration. Drug Indication Investigated for use/treatment in brain cancer and cancer/tumors (unspecified). Mechanism of Action ATN-161 is a non-RGD based integrin binding peptide targeting alpha-5 beta-1 and alpha-v beta-3. It inhibits the migration and adhesion of particular integrins on activated endothelial cells that play a critical role in tumor angiogenesis. Beta integrins, including beta(1), beta(3) and beta(5) subtypes, are present on endothelial cells and mediate endothelial cell-extracellular matrix interactions. Of particular interest to cancer progression is integrin alpha(5)beta(1) which is expressed on activated endothelial cells and plays a critical role in tumor angiogenesis. Likewise alpha(5)beta(1) integrin is also present on many tumor cells where is plays a key role in adhesion and migration and hence blocking this integrin can affect tumor progression both directly and also indirectly through the prevention of angiogenesis. Pharmacodynamics ATN-161 is a non-RGD based integrin binding peptide targeting alpha-5 beta-1 and alpha-v beta-3. It inhibits the migration and adhesion of particular integrins on activated endothelial cells that play a critical role in tumor angiogenesis. Since the over-expressed integrins and hyper-vasularized tissue is common across many cancer types, this treatment is expected to be indicated for many different cancers. |
Solubility Data
| Solubility (In Vitro) |
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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 (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 | 1.6732 mL | 8.3662 mL | 16.7325 mL | |
| 5 mM | 0.3346 mL | 1.6732 mL | 3.3465 mL | |
| 10 mM | 0.1673 mL | 0.8366 mL | 1.6732 mL |