ID: ALA1276127

Max Phase: Phase

Molecular Formula: C16H10N2O2

Molecular Weight: 262.27

Molecule Type: Small molecule

Representations

Synonyms (4): Couroupitine b | Indirubin | C.I. 75790 | NSC-105327
Synonyms from Alternative Forms(4):

Canonical SMILES:  O=C1Nc2ccccc2/C1=C1/Nc2ccccc2C1=O

Standard InChI:  InChI=1S/C16H10N2O2/c19-15-10-6-2-4-8-12(10)17-14(15)13-9-5-1-3-7-11(9)18-16(13)20/h1-8,17H,(H,18,20)/b14-13-

Standard InChI Key:  CRDNMYFJWFXOCH-YPKPFQOOSA-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: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 262.27

Molecular Weight (Monoisotopic): 262.0742

AlogP: 2.66

#Rotatable Bonds: 0

Polar Surface Area: 58.20

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 10.87

CX Basic pKa:

CX LogP: 2.43

CX LogD: 2.43

Aromatic Rings: 2

Heavy Atoms: 20

QED Weighted: 0.72

Np Likeness Score: 0.47

References

1. McGovern SL, Shoichet BK..  (2003)  Kinase inhibitors: not just for kinases anymore.,  46  (8): [PMID:12672248] [10.1021/jm020427b]

2. Guengerich FP, Sorrells JL, Schmitt S, Krauser JA, Aryal P, Meijer L..  (2004)  Generation of new protein kinase inhibitors utilizing cytochrome p450 mutant enzymes for indigoid synthesis.,  47  (12): [PMID:15163202] [10.1021/jm030561b]

3. Polychronopoulos P, Magiatis P, Skaltsounis AL, Myrianthopoulos V, Mikros E, Tarricone A, Musacchio A, Roe SM, Pearl L, Leost M, Greengard P, Meijer L..  (2004)  Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases.,  47  (4): [PMID:14761195] [10.1021/jm031016d]

4. Lee JW, Moon MJ, Min HY, Chung HJ, Park EJ, Park HJ, Hong JY, Kim YC, Lee SK..  (2005)  Induction of apoptosis by a novel indirubin-5-nitro-3'-monoxime, a CDK inhibitor, in human lung cancer cells.,  15  (17): [PMID:15993584] [10.1016/j.bmcl.2005.05.105]

5. Ferandin Y, Bettayeb K, Kritsanida M, Lozach O, Polychronopoulos P, Magiatis P, Skaltsounis AL, Meijer L..  (2006)  3'-Substituted 7-halogenoindirubins, a new class of cell death inducing agents.,  49  (15): [PMID:16854069] [10.1021/jm060314i]

6. Zhang L, Yu J, Pan H, Hu P, Hao Y, Cai W, Zhu H, Yu AD, Xie X, Ma D, Yuan J..  (2007)  Small molecule regulators of autophagy identified by an image-based high-throughput screen.,  104  (48): [PMID:18024584] [10.1073/pnas.0709695104]

7. Park EJ, Choi SJ, Kim YC, Lee SH, Park SW, Lee SK..  (2009)  Novel small molecule activators of beta-catenin-mediated signaling pathway: structure-activity relationships of indirubins.,  19  (8): [PMID:19282173] [10.1016/j.bmcl.2009.02.083]

8. Choi SJ, Moon MJ, Lee SD, Choi SU, Han SY, Kim YC..  (2010)  Indirubin derivatives as potent FLT3 inhibitors with anti-proliferative activity of acute myeloid leukemic cells.,  20  (6): [PMID:20153646] [10.1016/j.bmcl.2010.01.039]

9. Cheng X, Rasqué P, Vatter S, Merz KH, Eisenbrand G..  (2010)  Synthesis and cytotoxicity of novel indirubin-5-carboxamides.,  18  (12): [PMID:20488718] [10.1016/j.bmc.2010.04.066]

10. Caridha D, Kathcart AK, Jirage D, Waters NC..  (2010)  Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases.,  20  (13): [PMID:20627564] [10.1016/j.bmcl.2010.05.039]

11. Krivogorsky B, Grundt P, Yolken R, Jones-Brando L..  (2008)  Inhibition of Toxoplasma gondii by indirubin and tryptanthrin analogs.,  52  (12): [PMID:18824607] [10.1128/aac.00903-08]

12. PubChem BioAssay data set, 

13. PubChem BioAssay data set, 

14. PubChem BioAssay data set, 

15. PubChem BioAssay data set, 

16. PubChem BioAssay data set, 

17. Klöck C, Jin X, Choi K, Khosla C, Madrid PB, Spencer A, Raimundo BC, Boardman P, Lanza G, Griffin JH..  (2011)  Acylideneoxoindoles: a new class of reversible inhibitors of human transglutaminase 2.,  21  (9): [PMID:21215619] [10.1016/j.bmcl.2010.12.037]

18. Singh P, Kaur M, Holzer W..  (2010)  Synthesis and evaluation of indole, pyrazole, chromone and pyrimidine based conjugates for tumor growth inhibitory activities--development of highly efficacious cytotoxic agents.,  45  (11): [PMID:20810192] [10.1016/j.ejmech.2010.08.004]

19. Smyth LA, Matthews TP, Collins I..  (2011)  Design and evaluation of 3-aminopyrazolopyridinone kinase inhibitors inspired by the natural product indirubin.,  19  (11): [PMID:21536449] [10.1016/j.bmc.2011.03.069]

20. Saito H, Tabata K, Hanada S, Kanda Y, Suzuki T, Miyairi S..  (2011)  Synthesis of methoxy- and bromo-substituted indirubins and their activities on apoptosis induction in human neuroblastoma cells.,  21  (18): [PMID:21802947] [10.1016/j.bmcl.2011.07.011]

21. PubChem BioAssay data set, 

22. Chen M, Gan L, Lin S, Wang X, Li L, Li Y, Zhu C, Wang Y, Jiang B, Jiang J, Yang Y, Shi J..  (2012)  Alkaloids from the root of Isatis indigotica.,  75  (6): [PMID:22694318] [10.1021/np3002833]

23. Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P..  (2012)  Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.,  20  (22): [PMID:23062825] [10.1016/j.bmc.2012.09.040]

24. Klein LL, Petukhova V, Wan B, Wang Y, Santasiero BD, Lankin DC, Pauli GF, Franzblau SG..  (2014)  A novel indigoid anti-tuberculosis agent.,  24  (1): [PMID:24314672] [10.1016/j.bmcl.2013.11.024]

25. Cheng X, Merz KH, Vatter S, Christ J, Wölfl S, Eisenbrand G..  (2014)  7,7'-Diazaindirubin--a small molecule inhibitor of casein kinase 2 in vitro and in cells.,  22  (1): [PMID:24326279] [10.1016/j.bmc.2013.11.031]

26. Ichimaru Y, Saito H, Uchiyama T, Metori K, Tabata K, Suzuki T, Miyairi S..  (2015)  Indirubin 3'-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent.,  25  (7): [PMID:25765906] [10.1016/j.bmcl.2015.02.053]

27. Maqbool M, Mobashir M, Hoda N..  (2016)  Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer's disease.,  107  [PMID:26562543] [10.1016/j.ejmech.2015.10.018]

28. Evdokimov NM, Magedov IV, McBrayer D, Kornienko A..  (2016)  Isatin derivatives with activity against apoptosis-resistant cancer cells.,  26  (6): [PMID:26883150] [10.1016/j.bmcl.2016.02.015]

29. Jung ME, Byun BJ, Kim HM, Lee JY, Park JH, Lee N, Son YH, Choi SU, Yang KM, Kim SJ, Lee K, Kim YC, Choi G..  (2016)  Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening.,  26  (11): [PMID:27106709] [10.1016/j.bmcl.2016.03.111]

30. 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]

31. 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]

32. 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]

33. 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]

34. Wang J, Long L, Chen Y, Xu Y, Zhang L..  (2018)  Design, synthesis and antineoplastic activity of novel hybrids of podophyllotoxin and indirubin against human leukaemia cancer cells as multifunctional anti-MDR agents.,  28  (10): [PMID:29678463] [10.1016/j.bmcl.2018.04.019]

35. Karhu E, Isojärvi J, Vuorela P, Hanski L, Fallarero A..  (2017)  Identification of Privileged Antichlamydial Natural Products by a Ligand-Based Strategy.,  80  (10): [PMID:29043803] [10.1021/acs.jnatprod.6b01052]

36. 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]

37. Homer JA, Sperry J..  (2017)  Mushroom-Derived Indole Alkaloids.,  80  (7): [PMID:28722414] [10.1021/acs.jnatprod.7b00390]

38. Unpublished dataset, 

39. 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]

40. Tadesse S, Caldon EC, Tilley W, Wang S..  (2019)  Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update.,  62  (9): [PMID:30543440] [10.1021/acs.jmedchem.8b01469]

41. 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]

42. 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]

43. Cao Z, Yang F, Wang J, Gu Z, Lin S, Wang P, An J, Liu T, Li Y, Li Y, Lin H, Zhao Y, He B..  (2021)  Indirubin Derivatives as Dual Inhibitors Targeting Cyclin-Dependent Kinase and Histone Deacetylase for Treating Cancer.,  64  (20.0): [PMID:34624191] [10.1021/acs.jmedchem.1c01311]

44. Shi Z, Tian L, Qiang T, Li J, Xing Y, Ren X, Liu C, Liang C..  (2022)  From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer Therapy.,  65  (9.0): [PMID:35485642] [10.1021/acs.jmedchem.1c02064]

45. 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]

46. Lin L, Dai Y, Xia Y..  (2022)  An overview of aryl hydrocarbon receptor ligands in the Last two decades (2002-2022): A medicinal chemistry perspective.,  244  [PMID:36274276] [10.1016/j.ejmech.2022.114845]

Source

Source(4):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• SARS-CoV-2 Screening Data 2020-21