ATN-161 TFA, the trifluoroacetic acid salt of ATN161, is a novel and potent small peptide inhibitor of the integrin α5β1 with potential anticancer activity. It inhibits the angiogenesis and growth of liver metastases in a murine model. ATN-161 acts by interacting 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	C25H36F3N9O10S
Molecular Weight	711.67
Exact Mass	711.225
CAS #	904763-27-5
Related CAS #	ATN-161;262438-43-7
PubChem CID	92044380
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	10
Hydrogen Bond Acceptor Count	15
Rotatable Bond Count	15
Heavy Atom Count	48
Complexity	1100
Defined Atom Stereocenter Count	5
SMILES	CC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)N)C(=O)N.C(=O)(C(F)(F)F)O
InChi Key	MCVJOWHOEOLJGI-LQCLSJOXSA-N
InChi Code	InChI=1S/C23H35N9O8S.C2HF3O2/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;3-2(4,5)1(6)7/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);(H,6,7)/t13-,14-,15-,16-,17-;/m0./s1
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)succinamidetrifluoroacetic acid
Synonyms	AcPHSCNNH2; ATN161; ATN 161; ATN-161
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	The combination of ATN-161 trifluoroacetate salt and 5-FU significantly reduced tumor cell proliferation compared to control and single-drug treatments (p<0.01). Furthermore, combination treatment resulted in a substantial increase in apoptotic (TUNEL-positive) tumor cells (p<0.03), whereas single-agent treatment did not raise TUNEL-positive tumor cells. Treatment with ATN-161 trifluoroacetate salt resulted in a significant reduction (21% reduction) in EC numbers after 48 hours of incubation compared to the control (p<0.03)[1]. ATN-161 trifluoroacetate salt inhibits VEGF-induced hCEC migration and capillary tube formation, but not proliferation. Starting from 100 nM, ATN-161 trifluoroacetate salt reduced the number of cell migration in response to VEGF in a dose-dependent manner (P<0.001 compared with the VEGF group) [2].
ln Vivo	Treatment with ATN-161 trifluoroacetate salt significantly reduced tumor weight and vessel density in HT29 α5β1-negative human colon cancer xenografts, according to preliminary experiments [1]. The degree of inhibition of choroidal neovascularization (CNV) leakage and neovascularization that can be achieved by injecting ATN-161 trifluoroacetate salt following laser photocoagulation is comparable to that of AF564 [2].
Animal Protocol	saline; 0.05-1 mg/kg/d; i.v. BALB/c nu/nu mice
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.

Solubility Data

Solubility (In Vitro)	DMSO: > 10 mM Water: N/A Ethanol:N/A
Solubility (In Vivo)	Solubility in Formulation 1: 10 mg/mL (14.05 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4051 mL	7.0257 mL	14.0515 mL
	5 mM	0.2810 mL	1.4051 mL	2.8103 mL
	10 mM	0.1405 mL	0.7026 mL	1.4051 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.