Details of the Drug

General Information of Drug (ID: DM4T9RS)

Drug Name

ATN-161

Synonyms

PHSCN; PHSCN, University of Michigan; Angiogenesis inhibitors (cancer), Attenuon; Integrin antagonists (cancer), Attenuon; Ac-PHSCN-NH2, University of Michigan

Indication

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Phase 2	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 4

Molecular Weight (mw)

597.6

Topological Polar Surface Area (xlogp)

-4.7

Rotatable Bond Count (rotbonds)

15

Hydrogen Bond Donor Count (hbonddonor)

9

Hydrogen Bond Acceptor Count (hbondacc)

10

Chemical Identifiers

Formula: C23H35N9O8S
IUPAC Name: (2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-sulfanylpropanoyl]amino]butanediamide
Canonical 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
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
InChIKey: MMHDBUJXLOFTLC-WOYTXXSLSA-N

Cross-matching ID

PubChem CID: 9960285
CAS Number: 262438-43-7
DrugBank ID: DB05491
TTD ID: D00QVT

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Integrin alpha-5/beta-1 (ITGA5/B1)	TTH4QIS	ITA5_HUMAN-ITB1_HUMAN	Antagonist	[2]
Integrin alpha-V/beta-3 (ITGAV/B3)	TT69TQN	ITAV_HUMAN-ITB3_HUMAN	Antagonist	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Renal cell carcinoma

ICD Disease Classification

2C90

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Integrin alpha-5/beta-1 (ITGA5/B1)	DTT	ITGA5-ITGB1	2.88E-04	0.22	1.11
Integrin alpha-V/beta-3 (ITGAV/B3)	DTT	ITGAV-ITGB3	5.75E-01	-0.24	-0.5

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT00131651) ATN-161 in Advanced Renal Cell Cancer. U.S. National Institutes of Health.
2	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.
3	The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.PLoS One.2009;4(2):e4449.
4	A randomised, phase II study of intetumumab, an anti-alphav-integrin mAb, alone and with dacarbazine in stage IV melanoma. Br J Cancer. 2011 Jul 26;105(3):346-52.
5	AbbVie Licenses Phase II-Ready Antibody Programme to Receptos for Development in Eosinophilic Oesophagitis. 2013(4), Page 35.
6	Use of a novel Arg-Gly-Asp radioligand, 18F-AH111585, to determine changes in tumor vascularity after antitumor therapy.J Nucl Med.2009 Jan;50(1):116-22.
7	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
8	Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma.Gene Ther.2015 Jul;22(7):578-90.
9	Monoclonal antibodies to alphaVbeta3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor. Blood. 2000 Jan 15;95(2):368-74.
10	SB-267268, a nonpeptidic antagonist of alpha(v)beta3 and alpha(v)beta5 integrins, reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1600-5.
11	Disease-modifying activity of SB 273005, an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthri... Arthritis Rheum. 2001 Jan;44(1):128-37.
12	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
13	Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent. J Exp Ther Oncol. 2006;5(4):273-86.
14	US patent application no. 8,541,413, Sustained release eye drop formulations.