Synonym
ATN161; ATN 161; ATN-161; AcPHSCNNH2
IUPAC/Chemical Name
(S)-2-((R)-2-((S)-2-((S)-2-((S)-1-acetylpyrrolidine-2-carboxamido)-3-(1H-imidazol-5-yl)propanamido)-3-hydroxypropanamido)-3-mercaptopropanamido)succinamide
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
SMILES Code
O=C(N)[C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@H]1N(C(C)=O)CCC1)=O)CC2=CN=CN2)=O)CO)=O)CS)=O)CC(N)=O
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, soluble in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Note: The original catalog number for this product was 200350a.
Biological target:
Integrin α5β1 antagonist.
In vitro activity:
The binding of the SARS-CoV-2 spike protein with ACE2 and α5β1 was explored using ELISA-based methods. To determine the spike protein’s ability to bind α5β1, plates were coated with α5β1 and incubated with a mixture of ATN-161 and a trimeric version of the spike protein. The SARS-CoV-2 spike protein was bound to α5β1 with an affinity that was roughly equivalent to α5β1’s native ligand, fibronectin, and inhibited binding with a U-shaped, dose-dependent manner, with maximum effect at 100 nM (Figure 1A). This U-shaped response was not surprising because it was consistent with previous in vitro and in vivo studies on ATN-161 in the context of blocking angiogenesis and solid tumor growth. This might be due to the ability of ATN-161, at saturating concentrations, to affect the expression of α5β1 integrin, which was demonstrated to occur in experimental stroke.
Reference: JACC Basic Transl Sci. 2021 Jan;6(1):1-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566794/
In vivo activity:
Following tandem transient common carotid artery/middle cerebral artery occlusion on wild-type mice, the integrin a5b1 inhibitor, ATN-161, was administered by intraperitoneal (IP) injection at 1 mg/kg acutely after reperfusion, on post-stroke day (PSD)1 and PSD2. Systemic changes (heart rate, pulse distension, and body temperature) were determined. Additionally, infarct volume and edema were determined by 2,3-triphenyltetrazolium chloride and magnetic resonance imaging, while neurological changes were evaluated using an 11-point Neuroscore. Brain immunohistochemistry was performed for claudin-5, α5β1, IgG, and CD45 + cells, and quantitative polymerase chain reaction (qPCR) was performed for matrix metalloproteinase-9 (MMP-9), interleukin (IL)-1β, collagen IV, and CXCL12. ATN-161 significantly reduced integrin α5β1 expression in the surrounding peri-infarct region with no systemic changes. Infarct volume, edema, and functional deficit were significantly reduced in ATN-161-treated mice. Furthermore, ATN-161 treatment reduced IgG extravasation into the parenchyma through conserved claudin-5, collagen IV, CXCL12 while reducing MMP-9 transcription. Additionally, IL-1β and CD45 + cells were reduced in the ipsilateral cortex following ATN-161 administration.
Reference: J Cereb Blood Flow Metab. 2020 Aug;40(8):1695-1708. https://pubmed.ncbi.nlm.nih.gov/33102950/
|
Solvent |
mg/mL |
mM |
| Solubility |
| Water |
7.5 |
12.56 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
597.64
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Beddingfield BJ, Iwanaga N, Chapagain PP, Zheng W, Roy CJ, Hu TY, Kolls JK, Bix GJ. The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection. JACC Basic Transl Sci. 2021 Jan;6(1):1-8. doi: 10.1016/j.jacbts.2020.10.003. Epub 2020 Oct 16. PMID: 33102950; PMCID: PMC7566794.
2. Wang W, Wang F, Lu F, Xu S, Hu W, Huang J, Gu Q, Sun X. 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. doi: 10.1167/iovs.10-7097. PMID: 21813636.
3. Edwards DN, Salmeron K, Lukins DE, Trout AL, Fraser JF, Bix GJ. Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke. J Cereb Blood Flow Metab. 2020 Aug;40(8):1695-1708. doi: 10.1177/0271678X19880161. Epub 2019 Oct 1. PMID: 31575337; PMCID: PMC7370357.
4. Lv X, Li Z, Guan J, Zhang J, Xu B, He W, Lan Y, Zhao K, Lu H, Song D, Gao F. ATN-161 reduces virus proliferation in PHEV-infected mice by inhibiting the integrin α5β1-FAK signaling pathway. Vet Microbiol. 2019 Jun;233:147-153. doi: 10.1016/j.vetmic.2019.04.029. Epub 2019 Apr 26. PMID: 31176401.
In vitro protocol:
1. Beddingfield BJ, Iwanaga N, Chapagain PP, Zheng W, Roy CJ, Hu TY, Kolls JK, Bix GJ. The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection. JACC Basic Transl Sci. 2021 Jan;6(1):1-8. doi: 10.1016/j.jacbts.2020.10.003. Epub 2020 Oct 16. PMID: 33102950; PMCID: PMC7566794.
2. Wang W, Wang F, Lu F, Xu S, Hu W, Huang J, Gu Q, Sun X. 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. doi: 10.1167/iovs.10-7097. PMID: 21813636.
In vivo protocol:
1. Edwards DN, Salmeron K, Lukins DE, Trout AL, Fraser JF, Bix GJ. Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke. J Cereb Blood Flow Metab. 2020 Aug;40(8):1695-1708. doi: 10.1177/0271678X19880161. Epub 2019 Oct 1. PMID: 31575337; PMCID: PMC7370357.
2. Lv X, Li Z, Guan J, Zhang J, Xu B, He W, Lan Y, Zhao K, Lu H, Song D, Gao F. ATN-161 reduces virus proliferation in PHEV-infected mice by inhibiting the integrin α5β1-FAK signaling pathway. Vet Microbiol. 2019 Jun;233:147-153. doi: 10.1016/j.vetmic.2019.04.029. Epub 2019 Apr 26. PMID: 31176401.
1: Dai W, Yang T, Wang X, Wang J, Zhang X, Zhang Q. PHSCNK-Modified and doxorubicin-loaded liposomes as a dual targeting system to integrin-overexpressing tumor neovasculature and tumor cells. J Drug Target. 2010 May;18(4):254-63. PubMed PMID: 19824864.
2: Doñate F, Parry GC, Shaked Y, Hensley H, Guan X, Beck I, Tel-Tsur Z, Plunkett ML, Manuia M, Shaw DE, Kerbel RS, Mazar AP. Pharmacology of the novel antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2): observation of a U-shaped dose-response curve in several preclinical models of angiogenesis and tumor growth. Clin Cancer Res. 2008 Apr 1;14(7):2137-44. PubMed PMID: 18381955.
3: Danese S, Sans M, Spencer DM, Beck I, Doñate F, Plunkett ML, de la Motte C, Redline R, Shaw DE, Levine AD, Mazar AP, Fiocchi C. Angiogenesis blockade as a new therapeutic approach to experimental colitis. Gut. 2007 Jun;56(6):855-62. Epub 2006 Dec 14. PubMed PMID: 17170016.
4: Chidlow JH Jr, Langston W, Greer JJ, Ostanin D, Abdelbaqi M, Houghton J, Senthilkumar A, Shukla D, Mazar AP, Grisham MB, Kevil CG. Differential angiogenic regulation of experimental colitis. Am J Pathol. 2006 Dec;169(6):2014-30. PubMed PMID: 17148665; PubMed Central PMCID: PMC1762465.
5: Khalili P, Arakelian A, Chen G, Plunkett ML, Beck I, Parry GC, Doñate F, Shaw DE, Mazar AP, Rabbani SA. A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo. Mol Cancer Ther. 2006 Sep;5(9):2271-80. PubMed PMID: 16985061.
6: Cianfrocca ME, Kimmel KA, Gallo J, Cardoso T, Brown MM, Hudes G, Lewis N, Weiner L, Lam GN, Brown SC, Shaw DE, Mazar AP, Cohen RB. Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours. Br J Cancer. 2006 Jun 5;94(11):1621-6. PubMed PMID: 16705310; PubMed Central PMCID: PMC2361324.
7: Stoeltzing O, Liu W, Reinmuth N, Fan F, Parry GC, Parikh AA, McCarty MF, Bucana CD, Mazar AP, Ellis LM. 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. PubMed PMID: 12584749.
1. Amruta N, Bix G. ATN-161 Ameliorates Ischemia/Reperfusion-induced Oxidative Stress, Fibro-inflammation, Mitochondrial damage, and Apoptosis-mediated Tight Junction Disruption in bEnd.3 Cells. Inflammation. 2021 Aug 22:1–18. doi: 10.1007/s10753-021-01509-9. Epub ahead of print. PMID: 34420157; PMCID: PMC8380192.
2. Amruta N, Engler-Chiurazzi EB, Murray-Brown IC, Gressett TE, Biose IJ, Chastain WH, Befeler JB, Bix G. In Vivo protection from SARS-CoV-2 infection by ATN-161 in k18-hACE2 transgenic mice. Life Sci. 2021 Aug 10;284:119881. doi: 10.1016/j.lfs.2021.119881. Epub ahead of print. PMID: 34389403; PMCID: PMC8352850.
3. Hamblin MH, Murad R, Yin J, Vallim G, Lee JP. Modulation of gene expression on a transcriptome-wide level following human neural stem cell transplantation in aged mouse stroke brains. Exp Neurol. 2022 Jan;347:113913. doi: 10.1016/j.expneurol.2021.113913. Epub 2021 Nov 6. PMID: 34752785; PMCID: PMC8647207.
4. Edwards DN, Salmeron K, Lukins DE, Trout AL, Fraser JF, Bix GJ. Integrin α5β1 inhibition by ATN-161 reduces neuroinflammation and is neuroprotective in ischemic stroke. J Cereb Blood Flow Metab. 2020 Aug;40(8):1695-1708. doi: 10.1177/0271678X19880161. Epub 2019 Oct 1. PMID: 31575337; PMCID: PMC7370357.
5. Kawamura T, Yamamoto M, Suzuki K, Suzuki Y, Kamishima M, Sakata M, Kurachi K, Setoh M, Konno H, Takeuchi H. Tenascin-C Produced by Intestinal Myofibroblasts Promotes Colitis-associated Cancer Development Through Angiogenesis. Inflamm Bowel Dis. 2019 Mar 14;25(4):732-741. doi: 10.1093/ibd/izy368. PMID: 30517646.
6. Roberts J, de Hoog L, Bix GJ. Mice deficient in endothelial α5 integrin are profoundly resistant to experimental ischemic stroke. J Cereb Blood Flow Metab. 2017 Jan;37(1):85-96. doi: 10.1177/0271678X15616979. Epub 2015 Nov 13. PMID: 26661237; PMCID: PMC5363730.
7. Sundaram A, Chen C, Khalifeh-Soltani A, Atakilit A, Ren X, Qiu W, Jo H, DeGrado W, Huang X, Sheppard D. Targeting integrin α5β1 ameliorates severe airway hyperresponsiveness in experimental asthma. J Clin Invest. 2017 Jan 3;127(1):365-374. doi: 10.1172/JCI88555. Epub 2016 Dec 5. PMID: 27918306; PMCID: PMC5199700.
8. Leitner L, Schuch K, Jürets A, Itariu BK, Keck M, Grablowitz V, Aszmann OC, Prager G, Staffler G, Zeyda M, Stulnig TM. Immunological blockade of adipocyte inflammation caused by increased matrix metalloproteinase-cleaved osteopontin in obesity. Obesity (Silver Spring). 2015 Apr;23(4):779-85. doi: 10.1002/oby.21024. Epub 2015 Mar 16. PMID: 25776538.
9. Magdaleno C, Dixon L, Rajasekaran N, Varadaraj A. HIFα independent mechanisms in renal carcinoma cells modulate divergent outcomes in fibronectin assembly mediated by hypoxia and CoCl2. Sci Rep. 2020 Oct 29;10(1):18560. doi: 10.1038/s41598-020-75756-5. PMID: 33122751; PMCID: PMC7596723.
10. Liu H, Lee MJ, Solis NV, Phan QT, Swidergall M, Ralph B, Ibrahim AS, Sheppard DC, Filler SG. Aspergillus fumigatus CalA binds to integrin α5β1 and mediates host cell invasion. Nat Microbiol. 2016 Nov 14;2:16211. doi: 10.1038/nmicrobiol.2016.211. PMID: 27841851; PMCID: PMC5495140.
11. Lukas Leitner,. Effects of matrix metalloproteinase cleavage of osteopontin on human adipocyte function and their blockade with a monoclonal antibody. Doctoral thesis at the Medical University of Vienna. https://repositorium.meduniwien.ac.at/obvumwhs/content/titleinfo/2241469/full.pdf
12. Hamblin MH, Murad R, Yin J, Vallim G, Lee JP. Modulation of gene expression on a transcriptome-wide level following human neural stem cell transplantation in aged mouse stroke brains. Exp Neurol. 2022 Jan;347:113913. doi: 10.1016/j.expneurol.2021.113913. Epub 2021 Nov 6. PMID: 34752785; PMCID: PMC8647207.
