ID: ALA453539

Max Phase: Preclinical

Molecular Formula: C67H104N18O18S2

Molecular Weight: 1513.81

Molecule Type: Protein

Representations

Canonical SMILES:  CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2

Standard InChI:  InChI=1S/C67H104N18O18S2/c1-6-35(3)51-62(99)79-44-33-104-105-34-45(78-55(92)39(20-13-25-71-67(69)70)73-49(88)31-72-54(91)41(30-50(89)90)75-60(97)46-21-14-26-83(46)64(101)42(76-58(44)95)29-38-17-9-8-10-18-38)59(96)82-53(37(5)87)63(100)74-40(19-11-12-24-68)56(93)77-43(32-86)57(94)81-52(36(4)7-2)66(103)85-28-16-23-48(85)65(102)84-27-15-22-47(84)61(98)80-51/h8-10,17-18,35-37,39-48,51-53,86-87H,6-7,11-16,19-34,68H2,1-5H3,(H,72,91)(H,73,88)(H,74,100)(H,75,97)(H,76,95)(H,77,93)(H,78,92)(H,79,99)(H,80,98)(H,81,94)(H,82,96)(H,89,90)(H4,69,70,71)/t35-,36-,37+,39-,40-,41-,42-,43-,44-,45-,46-,47-,48-,51-,52-,53-/m0/s1

Standard InChI Key:  QQBRBPSSMDPLLA-GECFALDLSA-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: 1513.81

Molecular Weight (Monoisotopic): 1512.7217

AlogP:

#Rotatable Bonds:

Polar Surface Area:

Molecular Species:

HBA:

HBD:

#RO5 Violations:

HBA (Lipinski):

HBD (Lipinski):

#RO5 Violations (Lipinski):

CX Acidic pKa:

CX Basic pKa:

CX LogP:

CX LogD:

Aromatic Rings:

Heavy Atoms:

QED Weighted:

Np Likeness Score:

References

1. Łegowska A, Debowski D, Lesner A, Wysocka M, Rolka K..  (2009)  Introduction of non-natural amino acid residues into the substrate-specific P1 position of trypsin inhibitor SFTI-1 yields potent chymotrypsin and cathepsin G inhibitors.,  17  (9): [PMID:19362846] [10.1016/j.bmc.2009.03.045]

2. Łegowska A, Bulak E, Wysocka M, Jaśkiewicz A, Lesner A, Debowski D, Rolka K..  (2008)  Peptomeric analogues of trypsin inhibitor SFTI-1 isolated from sunflower seeds.,  16  (10): [PMID:18448341] [10.1016/j.bmc.2008.03.075]

3. Lęgowska A, Dębowski D, Lukajtis R, Wysocka M, Czaplewski C, Lesner A, Rolka K..  (2010)  Implication of the disulfide bridge in trypsin inhibitor SFTI-1 in its interaction with serine proteinases.,  18  (23): [PMID:21036622] [10.1016/j.bmc.2010.10.014]

4. Rothemund S, Sönnichsen FD, Polte T..  (2013)  Therapeutic potential of the peptide leucine arginine as a new nonplant bowman-birk-like serine protease inhibitor.,  56  (17): [PMID:23988198] [10.1021/jm4005362]

5. de Veer SJ, Wang CK, Harris JM, Craik DJ, Swedberg JE..  (2015)  Improving the Selectivity of Engineered Protease Inhibitors: Optimizing the P2 Prime Residue Using a Versatile Cyclic Peptide Library.,  58  (20): [PMID:26393374] [10.1021/acs.jmedchem.5b01148]

6. Wang CK, Northfield SE, Huang YH, Ramos MC, Craik DJ..  (2016)  Inhibition of tau aggregation using a naturally-occurring cyclic peptide scaffold.,  109  [PMID:26807864] [10.1016/j.ejmech.2016.01.006]

7. Qiu Y, Taichi M, Wei N, Yang H, Luo KQ, Tam JP..  (2017)  An Orally Active Bradykinin B1 Receptor Antagonist Engineered as a Bifunctional Chimera of Sunflower Trypsin Inhibitor.,  60  (1): [PMID:27977181] [10.1021/acs.jmedchem.6b01011]

8. Durek T, Cromm PM, White AM, Schroeder CI, Kaas Q, Weidmann J, Ahmad Fuaad A, Cheneval O, Harvey PJ, Daly NL, Zhou Y, Dellsén A, Österlund T, Larsson N, Knerr L, Bauer U, Kessler H, Cai M, Hruby VJ, Plowright AT, Craik DJ..  (2018)  Development of Novel Melanocortin Receptor Agonists Based on the Cyclic Peptide Framework of Sunflower Trypsin Inhibitor-1.,  61  (8): [PMID:29605997] [10.1021/acs.jmedchem.8b00170]

9. Swedberg JE, Li CY, de Veer SJ, Wang CK, Craik DJ..  (2017)  Design of Potent and Selective Cathepsin G Inhibitors Based on the Sunflower Trypsin Inhibitor-1 Scaffold.,  60  (2): [PMID:28045523] [10.1021/acs.jmedchem.6b01509]

10. de Veer SJ, Li CY, Swedberg JE, Schroeder CI, Craik DJ..  (2018)  Engineering potent mesotrypsin inhibitors based on the plant-derived cyclic peptide, sunflower trypsin inhibitor-1.,  155  [PMID:29936356] [10.1016/j.ejmech.2018.06.029]

11. Swedberg JE, Wu G, Mahatmanto T, Durek T, Caradoc-Davies TT, Whisstock JC, Law RHP, Craik DJ..  (2019)  Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 Scaffold Attenuate Fibrinolysis in Plasma.,  62  (2): [PMID:30520638] [10.1021/acs.jmedchem.8b01139]

12. Li CY, Yap K, Swedberg JE, Craik DJ, de Veer SJ..  (2020)  Binding Loop Substitutions in the Cyclic Peptide SFTI-1 Generate Potent and Selective Chymase Inhibitors.,  63  (2): [PMID:31855419] [10.1021/acs.jmedchem.9b01811]

13. Muratspahić E, Tomašević N, Koehbach J, Duerrauer L, Hadžić S, Castro J, Schober G, Sideromenos S, Clark RJ, Brierley SM, Craik DJ, Gruber CW..  (2021)  Design of a Stable Cyclic Peptide Analgesic Derived from Sunflower Seeds that Targets the κ-Opioid Receptor for the Treatment of Chronic Abdominal Pain.,  64  (13.0): [PMID:34162205] [10.1021/acs.jmedchem.1c00158]

Source

Source(1):

• Scientific Literature