ATN-161

• CAT Number: I002899
• CAS Number: 262438-43-7
• Molecular Formula: C23H35N9O8S
• Molecular Weight: 597.64
• Purity: ≥95%
• Target: Integrin antagonist
• Solubility: 10 mM in DMSO
• Storage: 3 years -20C powder
• InChI: 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-,1
• InChIKey: MMHDBUJXLOFTLC-WOYTXXSLSA-N
• SMILES: 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

ATN-161 (Ac-PHSCN-NH2) is a five -amino-acid peptide derived from the synergy region of fibronectin; a beta integrin antagonist with antitumor activity.IC50 value:Target: Integrin antagonistin vitro: ATN-161 inhibited VEGF-induced migration and capillary tube formation in hCECs, but did not inhibit proliferation [2].in vivo: Murine colon cancer cells (CT26) were injected into spleens of BALB/c mice to produce liver metastases. Four days thereafter, mice were given either ATN-161 (100 mg/kg, every 3rd day) or saline by intraperitoneal injection, with or without combination of continuous-infusion 5-FU (100 mg/kg/2 weeks), which was started on day 7. On day 20 after tumor cell inoculation, mice were killed and liver weights and number of liver metastases were determined [1]. ATN-161 after laser photocoagulation inhibited CNV leakage and neovascularization to an extent similar to AF564. Furthermore, SD-OCT and histologic examinations indicated that ATN-161 significantly decreased the size of laser-induced lesions [2]. Treatment with ATN-161 significantly blunts atherosclerotic plaque development in apolipoprotein E-deficient mice, characterized by reduced vascular cell adhesion molecule-1 expression and macrophage accumulation without affecting fibrous cap size.

Reference

1:ATN-161 Peptide Functionalized Reversibly Cross-Linked Polymersomes Mediate Targeted Doxorubicin Delivery into Melanoma-Bearing C57BL/6 Mice. Zhang N, Xia Y, Zou Y, Yang W, Zhang J, Zhong Z, Meng F.Mol Pharm. 2017 Jan 6. doi: 10.1021/acs.molpharmaceut.6b00800. [Epub ahead of print] PMID: 28005375 2:Joint Antiangiogenic Effect of ATN-161 and Anti-VEGF Antibody in a Rat Model of Early Wet Age-Related Macular Degeneration. Wang WQ, Wang FH, Qin WX, Liu HY, Lu B, Chung C, Zhu J, Gu Q, Shi W, Wen C, Wu F, Zhang K, Sun XD.Mol Pharm. 2016 Sep 6;13(9):2881-90. doi: 10.1021/acs.molpharmaceut.6b00056. Epub 2016 May 9. PMID: 27089240 3:The antiangiogenic effects of integrin alpha5beta1 inhibitor (ATN-161) in vitro and in vivo. Wang W, Wang F, Lu F, Xu S, Hu W, Huang J, Gu Q, Sun X.Invest Ophthalmol Vis Sci. 2011 Sep 14;52(10):7213-20. doi: 10.1167/iovs.10-7097. PMID: 21813636 4: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. 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.Clin Cancer Res. 2008 Apr 1;14(7):2137-44. doi: 10.1158/1078-0432.CCR-07-4530. PMID: 18381955 Free Article5:A non-RGD-based integrin binding peptide (ATN-161) blocks breast cancer growth and metastasis in vivo. Khalili P, Arakelian A, Chen G, Plunkett ML, Beck I, Parry GC, Doñate F, Shaw DE, Mazar AP, Rabbani SA.Mol Cancer Ther. 2006 Sep;5(9):2271-80. PMID: 16985061 Free Article6:Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours. 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.Br J Cancer. 2006 Jun 5;94(11):1621-6. PMID: 16705310 Free PMC Article7: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. Stoeltzing O, Liu W, Reinmuth N, Fan F, Parry GC, Parikh AA, McCarty MF, Bucana CD, Mazar AP, Ellis LM.Int J Cancer. 2003 Apr 20;104(4):496-503. PMID: 12584749 Free Article