Identification
- Generic Name
- ATN-161
- DrugBank Accession Number
- DB05491
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for ATN-161 (DB05491)
- Weight
- Average: 597.65
Monoisotopic: 597.232930297 - Chemical Formula
- C23H35N9O8S
- Synonyms
- Not Available
- External IDs
- ATN-161
- ATN-161 free base
Pharmacology
- Indication
Investigated for use/treatment in brain cancer and cancer/tumors (unspecified).
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
- 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.
- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- XW0H5LE42K
- CAS number
- 262438-43-7
- InChI Key
- MMHDBUJXLOFTLC-WOYTXXSLSA-N
- 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-,16-,17-/m0/s1
- IUPAC Name
- (2S)-2-[(2R)-2-[(2S)-2-[(2S)-2-{[(2S)-1-acetylpyrrolidin-2-yl]formamido}-3-(1H-imidazol-5-yl)propanamido]-3-hydroxypropanamido]-3-sulfanylpropanamido]butanediamide
- SMILES
- CC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(N)=O
References
- General References
- Danese S, Sans M, Spencer DM, Beck I, Donate 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. [Article]
- 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. [Article]
- Khalili P, Arakelian A, Chen G, Plunkett ML, Beck I, Parry GC, Donate 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. [Article]
- 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. [Article]
- 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. [Article]
- Parlakpinar H, Sahna E, Ozer MK, Ozugurlu F, Vardi N, Acet A: Physiological and pharmacological concentrations of melatonin protect against cisplatin-induced acute renal injury. J Pineal Res. 2002 Oct;33(3):161-6. [Article]
- Haas M, Spargo BH, Wit EJ, Meehan SM: Etiologies and outcome of acute renal insufficiency in older adults: a renal biopsy study of 259 cases. Am J Kidney Dis. 2000 Mar;35(3):433-47. [Article]
- Mendez-Picon G, Posner MP, McGeorge MB, Baquero A, Goldman MH, Monahanakumar T, Lee HM: The effect of delayed function on long term survival of renal allografts. Surg Gynecol Obstet. 1985 Oct;161(4):351-6. [Article]
- External Links
- PubChem Substance
- 347910170
- ChemSpider
- 8135892
- ChEMBL
- CHEMBL4297456
- ZINC
- ZINC000003924034
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Terminated Treatment Renal Cell Carcinoma (RCC) 1 1, 2 Completed Treatment Brain and Central Nervous System Tumors 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.139 mg/mL ALOGPS logP -1.9 ALOGPS logP -6.7 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 9.94 Chemaxon pKa (Strongest Basic) 6.74 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 9 Chemaxon Polar Surface Area 271.8 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 143.33 m3·mol-1 Chemaxon Polarizability 57.77 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 251.1888117 predictedDarkChem Lite v0.1.0 [M+H]+ 251.4819117 predictedDarkChem Lite v0.1.0 [M+Na]+ 251.6633117 predictedDarkChem Lite v0.1.0
Drug created at November 18, 2007 18:25 / Updated at May 10, 2021 12:36