ID: ALA522892

Max Phase: Phase

Molecular Formula: C21H21FN6O

Molecular Weight: 392.44

Molecule Type: Small molecule

Representations

Synonyms (6): Dovitinib | Tki-258 | CHIR-258 | GFKI-258 | NVP-TKI258 | TKI-258
Synonyms from Alternative Forms(6):

Canonical SMILES:  CN1CCN(c2ccc3nc(-c4c(N)c5c(F)cccc5[nH]c4=O)[nH]c3c2)CC1

Standard InChI:  InChI=1S/C21H21FN6O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29)

Standard InChI Key:  PIQCTGMSNWUMAF-UHFFFAOYSA-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: 392.44

Molecular Weight (Monoisotopic): 392.1761

AlogP: 2.54

#Rotatable Bonds: 2

Polar Surface Area: 94.04

Molecular Species: NEUTRAL

HBA: 5

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 7

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 8.56

CX Basic pKa: 7.87

CX LogP: 1.35

CX LogD: 1.04

Aromatic Rings: 4

Heavy Atoms: 29

QED Weighted: 0.49

Np Likeness Score: -1.30

References

1. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M, Lapointe GR, Feucht PH, Warne RL, Heise CC, Menezes D, Aardalen K, Ye H, He M, Le V, Vora J, Jansen JM, Wernette-Hammond ME, Harris AL..  (2009)  Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors.,  52  (2): [PMID:19113866] [10.1021/jm800790t]

2. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP..  (2008)  A quantitative analysis of kinase inhibitor selectivity.,  26  (1): [PMID:18183025] [10.1038/nbt1358]

3. Shallal HM, Russu WA..  (2011)  Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives.,  46  (6): [PMID:21429632] [10.1016/j.ejmech.2011.02.057]

4. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP..  (2011)  Comprehensive analysis of kinase inhibitor selectivity.,  29  (11): [PMID:22037378] [10.1038/nbt.1990]

5. PubChem BioAssay data set, 

6. PubChem BioAssay data set, 

7. Richters A, Ketzer J, Getlik M, Grütter C, Schneider R, Heuckmann JM, Heynck S, Sos ML, Gupta A, Unger A, Schultz-Fademrecht C, Thomas RK, Bauer S, Rauh D..  (2013)  Targeting gain of function and resistance mutations in Abl and KIT by hybrid compound design.,  56  (14): [PMID:23773153] [10.1021/jm4004076]

8. Patel PR, Sun H, Li SQ, Shen M, Khan J, Thomas CJ, Davis MI..  (2013)  Identification of potent Yes1 kinase inhibitors using a library screening approach.,  23  (15): [PMID:23787099] [10.1016/j.bmcl.2013.05.072]

9. Gao C, Cahya S, Nicolaou CA, Wang J, Watson IA, Cummins DJ, Iversen PW, Vieth M..  (2013)  Selectivity data: assessment, predictions, concordance, and implications.,  56  (17): [PMID:23937569] [10.1021/jm400798j]

10. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

11. Unpublished dataset, 

12. Bujak A, Stefaniak F, Zdzalik D, Grygielewicz P, Dymek B, Zagozda M, Gunerka P, Lamparska-Przybysz M, Dubiel K, Wieczorek M, Dzwonek K.  (2015)  Discovery of TRAF-2 and NCK-interacting kinase (TNIK) inhibitors by ligand-based virtual screening methods,  6  (8): [10.1039/C5MD00090D]

13. 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]

14. Cheng W, Wang M, Tian X, Zhang X..  (2017)  An overview of the binding models of FGFR tyrosine kinases in complex with small molecule inhibitors.,  126  [PMID:27914362] [10.1016/j.ejmech.2016.11.052]

15. 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]

16. 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]

17. 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]

18. 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]

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. Kuriwaki I, Kameda M, Hisamichi H, Kikuchi S, Iikubo K, Kawamoto Y, Moritomo H, Kondoh Y, Amano Y, Tateishi Y, Echizen Y, Iwai Y, Noda A, Tomiyama H, Suzuki T, Hirano M..  (2020)  Structure-based drug design of 1,3,5-triazine and pyrimidine derivatives as novel FGFR3 inhibitors with high selectivity over VEGFR2.,  28  (10): [PMID:32278710] [10.1016/j.bmc.2020.115453]

21.  (2020)  Compositions and methods for treating beta-globinopathies, 

22. 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]

23. Cao S, Ma L, Liu Y, Wei M, Yao Y, Li C, Wang R, Liu N, Dong Z, Li X, Li M, Wang X, Yang C, Yang G..  (2021)  Proteolysis-Targeting Chimera (PROTAC) Modification of Dovitinib Enhances the Antiproliferative Effect against FLT3-ITD-Positive Acute Myeloid Leukemia Cells.,  64  (22.0): [PMID:34694800] [10.1021/acs.jmedchem.1c00996]

24. Yamani A, Zdżalik-Bielecka D, Lipner J, Stańczak A, Piórkowska N, Stańczak PS, Olejkowska P, Hucz-Kalitowska J, Magdycz M, Dzwonek K, Dubiel K, Lamparska-Przybysz M, Popiel D, Pieczykolan J, Wieczorek M..  (2021)  Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3).,  210  [PMID:33199155] [10.1016/j.ejmech.2020.112990]

25. Zattoni IF, Delabio LC, Dutra JP, Kita DH, Scheiffer G, Hembecker M, Pereira GDS, Moure VR, Valdameri G..  (2022)  Targeting breast cancer resistance protein (BCRP/ABCG2): Functional inhibitors and expression modulators.,  237  [PMID:35483322] [10.1016/j.ejmech.2022.114346]

26. Wang W, He S, Dong G, Sheng C..  (2022)  Nucleic-Acid-Based Targeted Degradation in Drug Discovery.,  65  (15.0): [PMID:35916496] [10.1021/acs.jmedchem.2c00875]

27. Shi K, Zhang J, Zhou E, Wang J, Wang Y..  (2022)  Small-Molecule Receptor-Interacting Protein 1 (RIP1) Inhibitors as Therapeutic Agents for Multifaceted Diseases: Current Medicinal Chemistry Insights and Emerging Opportunities.,  65  (22.0): [PMID:36346971] [10.1021/acs.jmedchem.2c01518]

28. Cilibrasi V, Spanò V, Bortolozzi R, Barreca M, Raimondi MV, Rocca R, Maruca A, Montalbano A, Alcaro S, Ronca R, Viola G, Barraja P..  (2022)  Synthesis of 2H-Imidazo[2',1':2,3] [1,3]thiazolo[4,5-e]isoindol-8-yl-phenylureas with promising therapeutic features for the treatment of acute myeloid leukemia (AML) with FLT3/ITD mutations.,  235  [PMID:35339838] [10.1016/j.ejmech.2022.114292]

29. Liang Q, Wang J, Zhao L, Hou J, Hu Y, Shi J..  (2021)  Recent advances of dual FGFR inhibitors as a novel therapy for cancer.,  214  [PMID:33556787] [10.1016/j.ejmech.2021.113205]

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

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

Source

Source(9):

• Scientific Literature
• PubChem BioAssays
• Clinical Candidates
• AstraZeneca Deposited Data
• Patent Bioactivity Data
• Kuster lab chemical proteomics drug profiling
• SARS-CoV-2 Screening Data 2020-21
• Fraunhofer HDAC6
• EU-OPENSCREEN dataset