ID: ALA409450

Max Phase: Preclinical

Molecular Formula: C16H10BrN3O2

Molecular Weight: 356.18

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=C1Nc2cc(Br)ccc2/C1=C1/Nc2ccccc2/C1=N\O

Standard InChI:  InChI=1S/C16H10BrN3O2/c17-8-5-6-9-12(7-8)19-16(21)13(9)15-14(20-22)10-3-1-2-4-11(10)18-15/h1-7,18,22H,(H,19,21)/b15-13-,20-14+

Standard InChI Key:  DDLZLOKCJHBUHD-WAVHTBQISA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 356.18

Molecular Weight (Monoisotopic): 354.9956

AlogP: 3.42

#Rotatable Bonds: 0

Polar Surface Area: 73.72

Molecular Species: NEUTRAL

HBA: 4

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 6.89

CX Basic pKa: 0.96

CX LogP: 2.56

CX LogD: 1.94

Aromatic Rings: 2

Heavy Atoms: 22

QED Weighted: 0.38

Np Likeness Score: 0.17

References

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20. Pergola C, Gaboriaud-Kolar N, Jestädt N, König S, Kritsanida M, Schaible AM, Li H, Garscha U, Weinigel C, Barz D, Albring KF, Huber O, Skaltsounis AL, Werz O..  (2014)  Indirubin core structure of glycogen synthase kinase-3 inhibitors as novel chemotype for intervention with 5-lipoxygenase.,  57  (9): [PMID:24697244] [10.1021/jm401740w]

21. Beniddir MA, Le Borgne E, Iorga BI, Loaëc N, Lozach O, Meijer L, Awang K, Litaudon M..  (2014)  Acridone alkaloids from Glycosmis chlorosperma as DYRK1A inhibitors.,  77  (5): [PMID:24798019] [10.1021/np400856h]

22. 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]

23. Cheng X, Merz KH, Vatter S, Zeller J, Muehlbeyer S, Thommet A, Christ J, Wölfl S, Eisenbrand G..  (2017)  Identification of a Water-Soluble Indirubin Derivative as Potent Inhibitor of Insulin-like Growth Factor 1 Receptor through Structural Modification of the Parent Natural Molecule.,  60  (12): [PMID:28557430] [10.1021/acs.jmedchem.7b00324]

24. Khan I, Tantray MA, Alam MS, Hamid H..  (2017)  Natural and synthetic bioactive inhibitors of glycogen synthase kinase.,  125  [PMID:27689729] [10.1016/j.ejmech.2016.09.058]

25. Gaboriaud-Kolar N, Myrianthopoulos V, Vougogiannopoulou K, Gerolymatos P, Horne DA, Jove R, Mikros E, Nam S, Skaltsounis AL..  (2016)  Natural-Based Indirubins Display Potent Cytotoxicity toward Wild-Type and T315I-Resistant Leukemia Cell Lines.,  79  (10): [PMID:27726390] [10.1021/acs.jnatprod.6b00285]

26. Ichimaru Y, Fujii T, Saito H, Sano M, Uchiyama T, Miyairi S..  (2017)  5-Bromoindirubin 3'-(O-oxiran-2-ylmethyl)oxime: A long-acting anticancer agent and a suicide inhibitor for epoxide hydrolase.,  25  (17): [PMID:28743492] [10.1016/j.bmc.2017.07.009]

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28. Kosuge Y, Saito H, Haraguchi T, Ichimaru Y, Ohashi S, Miyagishi H, Kobayashi S, Ishige K, Miyairi S, Ito Y..  (2017)  Indirubin derivatives protect against endoplasmic reticulum stress-induced cytotoxicity and down-regulate CHOP levels in HT22 cells.,  27  (23): [PMID:29122482] [10.1016/j.bmcl.2017.10.069]

29. 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]

30. Jorda R, Hendrychová D, Voller J, Řezníčková E, Gucký T, Kryštof V..  (2018)  How Selective Are Pharmacological Inhibitors of Cell-Cycle-Regulating Cyclin-Dependent Kinases?,  61  (20): [PMID:30234987] [10.1021/acs.jmedchem.8b00049]

31. 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]

32. 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]

33. 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]

34. 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]

35. Kim WH,Jeong P,Kim SW,Cho H,Lee JM,Seo S,Shen H,Ahn Y,Jung DW,Kim YC,Williams DR.  (2019)  A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity.,  27  (13.0): [PMID:31147141] [10.1016/j.bmc.2019.05.025]

36. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

37. Gilda Padalino, Avril Coghlan, Giampaolo Pagliuca, Josephine F. Thomas, Matthew Berriman, Karl F. Hoffmann.  (2023)  Using ChEMBL to complement schistosome drug discovery,  [10.6019/CHEMBL5096127]

38. Wang H, Wang Z, Wei C, Wang J, Xu Y, Bai G, Yao Q, Zhang L, Chen Y..  (2021)  Anticancer potential of indirubins in medicinal chemistry: Biological activity, structural modification, and structure-activity relationship.,  223  [PMID:34161865] [10.1016/j.ejmech.2021.113652]

39. Li H, Mattingly AE, Smith RD, Melander RJ, Ernst RK, Melander C..  (2023)  6-Bromoindirubin-3'-oxime derivatives are highly active colistin adjuvants against Klebsiella pneumoniae.,  14  (2.0): [PMID:36846374] [10.1039/d2md00370h]

40. Fraunhofer Institute for Translational Medicine and Pharmacology - Discovery Research – ScreeningPort.  (2021)  ECBD screening data for assay EOS300033,  [10.6019/EOS300033]

41. Institute for Molecular Medicine Finland - High Throughput Biomedicine Unit.  (2023)  ECBD screening data for assay EOS300108,  [10.6019/EOS300108]

Source

Source(5):

• Scientific Literature
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6
• Cardiff Schistosomiasis Dataset 2023
• EU-OPENSCREEN dataset