ID: ALA411941

Max Phase: Preclinical

Molecular Formula: C26H38N8O7

Molecular Weight: 574.64

Molecule Type: Protein

Representations

Canonical SMILES:  CC(C)[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC1=O

Standard InChI:  InChI=1S/C26H38N8O7/c1-14(2)21-25(41)32-16(9-6-10-29-26(27)28)22(38)30-13-19(35)31-18(12-20(36)37)23(39)33-17(24(40)34-21)11-15-7-4-3-5-8-15/h3-5,7-8,14,16-18,21H,6,9-13H2,1-2H3,(H,30,38)(H,31,35)(H,32,41)(H,33,39)(H,34,40)(H,36,37)(H4,27,28,29)/t16-,17+,18-,21-/m0/s1

Standard InChI Key:  YYQUWEHEBOMRPH-NYUBLWNDSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Protein

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 574.64

Molecular Weight (Monoisotopic): 574.2863

AlogP: -2.52

#Rotatable Bonds: 9

Polar Surface Area: 247.20

Molecular Species: ZWITTERION

HBA: 7

HBD: 8

#RO5 Violations: 2

HBA (Lipinski): 15

HBD (Lipinski): 10

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 3.93

CX Basic pKa: 10.35

CX LogP: -3.96

CX LogD: -3.96

Aromatic Rings: 1

Heavy Atoms: 41

QED Weighted: 0.09

Np Likeness Score: 1.31

References

1. Meinecke R, Meyer B..  (2001)  Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin alphaIIbbeta3.,  44  (19): [PMID:11543674] [10.1021/jm0109154]

2. Burgess K, Lim D, Mousa SA..  (1996)  Synthesis and solution conformation of cyclo[RGDRGD]: a cyclic peptide with selectivity for the alpha V beta 3 receptor.,  39  (22): [PMID:8893849] [10.1021/jm960276a]

3. Casiraghi G, Rassu G, Auzzas L, Burreddu P, Gaetani E, Battistini L, Zanardi F, Curti C, Nicastro G, Belvisi L, Motto I, Castorina M, Giannini G, Pisano C..  (2005)  Grafting aminocyclopentane carboxylic acids onto the RGD tripeptide sequence generates low nanomolar alphaVbeta3/alphaVbeta5 integrin dual binders.,  48  (24): [PMID:16302808] [10.1021/jm050698x]

4. Dal Pozzo A, Ni M, Muzi L, de Castiglione R, Mondelli R, Mazzini S, Penco S, Pisano C, Castorina M, Giannini G..  (2006)  Incorporation of the unusual C(alpha)-fluoroalkylamino acids into cyclopeptides: synthesis of arginine-glycine-aspartate (RGD) analogues and study of their conformational and biological behavior.,  49  (5): [PMID:16509596] [10.1021/jm0511334]

5. Becker OM, Dhanoa DS, Marantz Y, Chen D, Shacham S, Cheruku S, Heifetz A, Mohanty P, Fichman M, Sharadendu A, Nudelman R, Kauffman M, Noiman S..  (2006)  An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression.,  49  (11): [PMID:16722631] [10.1021/jm0508641]

6. Del Gatto A, Zaccaro L, Grieco P, Novellino E, Zannetti A, Del Vecchio S, Iommelli F, Salvatore M, Pedone C, Saviano M..  (2006)  Novel and selective alpha(v)beta3 receptor peptide antagonist: design, synthesis, and biological behavior.,  49  (11): [PMID:16722662] [10.1021/jm060233m]

7. Zhou Y, Peng H, Ji Q, Qi J, Zhu Z, Yang C..  (2006)  Discovery of small molecule inhibitors of integrin alphavbeta3 through structure-based virtual screening.,  16  (22): [PMID:16982193] [10.1016/j.bmcl.2006.08.061]

8. Zeng GZ, Tan NH, Hao XJ, Mu QZ, Li RT..  (2006)  Natural inhibitors targeting osteoclast-mediated bone resorption.,  16  (24): [PMID:17027271] [10.1016/j.bmcl.2006.09.042]

9. Salvati M, Cordero FM, Pisaneschi F, Melani F, Gratteri P, Cini N, Bottoncetti A, Brandi A..  (2008)  Synthesis, SAR and in vitro evaluation of new cyclic Arg-Gly-Asp pseudopentapeptides containing a s-cis peptide bond as integrin alphavbeta3 and alphavbeta5 ligands.,  16  (8): [PMID:18343671] [10.1016/j.bmc.2008.02.080]

10. Letourneau JJ, Liu J, Ohlmeyer MH, Riviello C, Rong Y, Li H, Appell KC, Bansal S, Jacob B, Wong A, Webb ML..  (2009)  Synthesis and initial evaluation of novel, non-peptidic antagonists of the alpha(v)-integrins alpha(v)beta(3) and alpha(v)beta(5).,  19  (2): [PMID:19081719] [10.1016/j.bmcl.2008.11.074]

11. Gentilucci L, Cardillo G, Spampinato S, Tolomelli A, Squassabia F, De Marco R, Bedini A, Baiula M, Belvisi L, Civera M..  (2010)  Antiangiogenic effect of dual/selective alpha(5)beta(1)/alpha(v)beta(3) integrin antagonists designed on partially modified retro-inverso cyclotetrapeptide mimetics.,  53  (1): [PMID:20055426] [10.1021/jm9013532]

12. Ye Y, Xu B, Nikiforovich GV, Bloch S, Achilefu S..  (2011)  Exploring new near-infrared fluorescent disulfide-based cyclic RGD peptide analogs for potential integrin-targeted optical imaging.,  21  (7): [PMID:21349709] [10.1016/j.bmcl.2011.01.133]

13. PubChem BioAssay data set, 

14. Colombo R, Mingozzi M, Belvisi L, Arosio D, Piarulli U, Carenini N, Perego P, Zaffaroni N, De Cesare M, Castiglioni V, Scanziani E, Gennari C..  (2012)  Synthesis and biological evaluation (in vitro and in vivo) of cyclic arginine-glycine-aspartate (RGD) peptidomimetic-paclitaxel conjugates targeting integrin αVβ3.,  55  (23): [PMID:23140358] [10.1021/jm301058f]

15. Nahrwold M, Weiß C, Bogner T, Mertink F, Conradi J, Sammet B, Palmisano R, Royo Gracia S, Preuße T, Sewald N..  (2013)  Conjugates of modified cryptophycins and RGD-peptides enter target cells by endocytosis.,  56  (5): [PMID:23387527] [10.1021/jm301346z]

16. Galletti P, Soldati R, Pori M, Durso M, Tolomelli A, Gentilucci L, Dattoli SD, Baiula M, Spampinato S, Giacomini D..  (2014)  Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives.,  83  [PMID:24973662] [10.1016/j.ejmech.2014.06.041]

17. Sartori A, Portioli E, Battistini L, Calorini L, Pupi A, Vacondio F, Arosio D, Bianchini F, Zanardi F..  (2017)  Synthesis of Novel c(AmpRGD)-Sunitinib Dual Conjugates as Molecular Tools Targeting the αvβ3 Integrin/VEGFR2 Couple and Impairing Tumor-Associated Angiogenesis.,  60  (1): [PMID:27997164] [10.1021/acs.jmedchem.6b01266]

18. Kobayakawa T, Matsuzaki Y, Hozumi K, Nomura W, Nomizu M, Tamamura H..  (2018)  Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its Biological Application.,  9  (1): [PMID:29348803] [10.1021/acsmedchemlett.7b00234]

19. Nardelli F, Paissoni C, Quilici G, Gori A, Traversari C, Valentinis B, Sacchi A, Corti A, Curnis F, Ghitti M, Musco G..  (2018)  Succinimide-Based Conjugates Improve IsoDGR Cyclopeptide Affinity to αvβ3 without Promoting Integrin Allosteric Activation.,  61  (17): [PMID:29883545] [10.1021/acs.jmedchem.8b00745]

20. Kemker I, Schnepel C, Schröder DC, Marion A, Sewald N..  (2019)  Cyclization of RGD Peptides by Suzuki-Miyaura Cross-Coupling.,  62  (16): [PMID:31306009] [10.1021/acs.jmedchem.9b00360]

21. Baiula M,Galletti P,Martelli G,Soldati R,Belvisi L,Civera M,Dattoli SD,Spampinato SM,Giacomini D.  (2016)  New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins.,  59  (21): [PMID:27726366] [10.1021/acs.jmedchem.6b00576]

Source

Source(2):

• Scientific Literature
• PubChem BioAssays