ID: ALA783

Max Phase: Approved

First Approval: 2000

Molecular Formula: C19H27NO3

Molecular Weight: 317.43

Molecule Type: Small molecule

Representations

Synonyms (11): D-nateglinide | Nateglinide | Senaglinide | A-4166 | AY-4166 | AY4166 | DJN 608 | DJN-608 | NSC-758695 | SDZ DJN 608 | SDZ-DJN-608
Synonyms from Alternative Forms(11):

Trade Names(3): Nateglinide | Starlix | Starsis

Canonical SMILES:  CC(C)[C@H]1CC[C@H](C(=O)N[C@H](Cc2ccccc2)C(=O)O)CC1

Standard InChI:  InChI=1S/C19H27NO3/c1-13(2)15-8-10-16(11-9-15)18(21)20-17(19(22)23)12-14-6-4-3-5-7-14/h3-7,13,15-17H,8-12H2,1-2H3,(H,20,21)(H,22,23)/t15-,16-,17-/m1/s1

Standard InChI Key:  OELFLUMRDSZNSF-BRWVUGGUSA-N

Molecule Features

Natural Product: Yes

Oral: Yes

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: Yes

Prodrug: No

Properties

Molecular Weight: 317.43

Molecular Weight (Monoisotopic): 317.1991

AlogP: 3.26

#Rotatable Bonds: 6

Polar Surface Area: 66.40

Molecular Species: ACID

HBA: 2

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 4.00

CX Basic pKa:

CX LogP: 4.03

CX LogD: 0.87

Aromatic Rings: 1

Heavy Atoms: 23

QED Weighted: 0.85

Np Likeness Score: -0.23

References

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15. Sakatis MZ, Reese MJ, Harrell AW, Taylor MA, Baines IA, Chen L, Bloomer JC, Yang EY, Ellens HM, Ambroso JL, Lovatt CA, Ayrton AD, Clarke SE..  (2012)  Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.,  25  (10): [PMID:22931300] [10.1021/tx300075j]

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17. Okamura A, Emoto A, Koyabu N, Ohtani H, Sawada Y..  (2002)  Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1.,  137  (1): [PMID:12237260] [10.1038/sj.bjp.0704875]

18. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K..  (2000)  Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.,  392  (1): [PMID:10748266] [10.1016/s0014-2999(00)00119-9]

19. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

20. Kaur J, Bhardwaj A, Huang Z, Narang D, Chen TY, Plane F, Knaus EE..  (2012)  Synthesis and biological investigations of nitric oxide releasing nateglinide and meglitinide type II antidiabetic prodrugs: in-vivo antihyperglycemic activities and blood pressure lowering studies.,  55  (17): [PMID:22916833] [10.1021/jm300997w]

21. Maddi S, Yamsani SK, Devandla A, Scriba G, Yamsani MR.  (2013)  Evidence of stereoselective and segmental-dependant transport of chiral antidiabetic drug nateglinide along the rat small intestine: possible role of efflux transporters,  22  (5): [10.1007/s00044-012-0234-4]

22. Maddi S, Yamsani SK, Devandla A, Scriba G, Yamsani MR.  (2013)  Evidence of stereoselective and segmental-dependant transport of chiral antidiabetic drug nateglinide along the rat small intestine: possible role of efflux transporters,  22  (5): [10.1007/s00044-012-0234-4]

23. PubChem BioAssay data set, 

24. De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP..  (2013)  Structure-based identification of OATP1B1/3 inhibitors.,  83  (6): [PMID:23571415] [10.1124/mol.112.084152]

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26. Digiacomo M, Martelli A, Testai L, Lapucci A, Breschi MC, Calderone V, Rapposelli S..  (2015)  Synthesis and evaluation of multi-functional NO-donor/insulin-secretagogue derivatives for the treatment of type II diabetes and its cardiovascular complications.,  23  (3): [PMID:25577707] [10.1016/j.bmc.2014.12.043]

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32. Unpublished dataset, 

33. Franck Touret, Magali Gilles, Karine Barral, Antoine Nougairède, Etienne Decroly, Xavier de Lamballerie, Bruno Coutard.  (2020)  In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication,  [10.1101/2020.04.03.023846]

34. Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek.  (2020)  Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection,  [10.21203/rs.3.rs-23951/v1]

35. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

36. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

37. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of NIH (USA) - Clinical Collection,  [10.6019/CHEMBL4513141]

38. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

39. European Medicines Agency, 

Source

Source(13):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book)
• USP Dictionary of USAN and International Drug Names
• DrugMatrix
• TP-search Transporter Database
• CO-ADD antimicrobial screening data
• WHO Anatomical Therapeutic Chemical Classification
• British National Formulary
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data
• European Medicines Agency