ID: ALA91829

Max Phase: Phase

Molecular Formula: C28H28N4O3

Molecular Weight: 468.56

Molecule Type: Small molecule

Representations

Synonyms (3): Ly-333531 | Ruboxistaurin | LY-333531
Synonyms from Alternative Forms(3):

Trade Names(1): Arxxant

Canonical SMILES:  CN(C)C[C@@H]1CCn2cc(c3ccccc32)C2=C(C(=O)NC2=O)c2cn(c3ccccc23)CCO1

Standard InChI:  InChI=1S/C28H28N4O3/c1-30(2)15-18-11-12-31-16-21(19-7-3-5-9-23(19)31)25-26(28(34)29-27(25)33)22-17-32(13-14-35-18)24-10-6-4-8-20(22)24/h3-10,16-18H,11-15H2,1-2H3,(H,29,33,34)/t18-/m0/s1

Standard InChI Key:  ZCBUQCWBWNUWSU-SFHVURJKSA-N

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 468.56

Molecular Weight (Monoisotopic): 468.2161

AlogP: 3.51

#Rotatable Bonds: 2

Polar Surface Area: 68.50

Molecular Species: BASE

HBA: 6

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 9.76

CX Basic pKa: 8.75

CX LogP: 2.98

CX LogD: 1.85

Aromatic Rings: 4

Heavy Atoms: 35

QED Weighted: 0.46

Np Likeness Score: -0.11

References

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

12. Drygin D, Haddach M, Pierre F, Ryckman DM..  (2012)  Potential use of selective and nonselective Pim kinase inhibitors for cancer therapy.,  55  (19): [PMID:22924342] [10.1021/jm3009234]

13. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S..  (2007)  A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.,  104  (51): [PMID:18077363] [10.1073/pnas.0708800104]

14. Zamek-Gliszczynski MJ, Abraham TL, Alberts JJ, Kulanthaivel P, Jackson KA, Chow KH, McCann DJ, Hu H, Anderson S, Furr NA, Barbuch RJ, Cassidy KC..  (2013)  Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure.,  41  (4): [PMID:23305709] [10.1124/dmd.112.048488]

15. Unpublished dataset, 

16. Klaeger S, Heinzlmeir S and Wilhelm M et al.  (2017)  The target landscape of clinical kinase drugs.,  358  (6367): [PMID:29191878] [10.1126/science.aan4368]

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18. 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]

19. 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]

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

21. Němec V,Maier L,Berger BT,Chaikuad A,Drápela S,Souček K,Knapp S,Paruch K.  (2021)  Highly selective inhibitors of protein kinases CLK and HIPK with the furo[3,2-b]pyridine core.,  215  [PMID:33636538] [10.1016/j.ejmech.2021.113299]

22.  (2020)  Compositions and methods for treating beta-globinopathies, 

23. Bijian K, Wernic D, Nivedha AK, Su J, Lim FPL, Miron CE, Amzil H, Moitessier N, Alaoui-Jamali MA..  (2022)  Novel Aurora A and Protein Kinase C (α, β1, β2, and θ) Multitarget Inhibitors: Impact of Selenium Atoms on the Potency and Selectivity.,  65  (4.0): [PMID:35167283] [10.1021/acs.jmedchem.1c01031]

Source

Source(7):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• Patent Bioactivity Data
• Kuster lab chemical proteomics drug profiling
• SARS-CoV-2 Screening Data 2020-21
• IMI-CARE SARS-CoV-2 Data