ID: ALA1233528

Max Phase: Phase

Molecular Formula: C34H50N8O3

Molecular Weight: 618.83

Molecule Type: Small molecule

Representations

Synonyms (5): Bi-6727 | Volasertib | BI 6727 | BI-6727 | BI6727
Synonyms from Alternative Forms(5):

Canonical SMILES:  CC[C@@H]1C(=O)N(C)c2cnc(Nc3ccc(C(=O)N[C@H]4CC[C@H](N5CCN(CC6CC6)CC5)CC4)cc3OC)nc2N1C(C)C

Standard InChI:  InChI=1S/C34H50N8O3/c1-6-28-33(44)39(4)29-20-35-34(38-31(29)42(28)22(2)3)37-27-14-9-24(19-30(27)45-5)32(43)36-25-10-12-26(13-11-25)41-17-15-40(16-18-41)21-23-7-8-23/h9,14,19-20,22-23,25-26,28H,6-8,10-13,15-18,21H2,1-5H3,(H,36,43)(H,35,37,38)/t25-,26-,28-/m1/s1

Standard InChI Key:  SXNJFOWDRLKDSF-STROYTFGSA-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: 618.83

Molecular Weight (Monoisotopic): 618.4006

AlogP: 4.27

#Rotatable Bonds: 10

Polar Surface Area: 106.17

Molecular Species: BASE

HBA: 9

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 12.25

CX Basic pKa: 8.70

CX LogP: 4.20

CX LogD: 2.89

Aromatic Rings: 2

Heavy Atoms: 45

QED Weighted: 0.40

Np Likeness Score: -1.26

References

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

2. Zhang Q, Xia Z, Mitten MJ, Lasko LM, Klinghofer V, Bouska J, Johnson EF, Penning TD, Luo Y, Giranda VL, Shoemaker AR, Stewart KD, Djuric SW, Vasudevan A..  (2012)  Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors.,  22  (24): [PMID:23103095] [10.1016/j.bmcl.2012.10.009]

3. Unpublished dataset, 

4. Rosse G..  (2016)  Dihydropteridinone Inhibitors of BRD4.,  7  (2): [PMID:26985285] [10.1021/acsmedchemlett.5b00381]

5. Talele TT..  (2016)  The "Cyclopropyl Fragment" is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules.,  59  (19): [PMID:27299736] [10.1021/acs.jmedchem.6b00472]

6. Munoz L..  (2017)  Non-kinase targets of protein kinase inhibitors.,  16  (6): [PMID:28280261] [10.1038/nrd.2016.266]

7. 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]

8. 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]

9. Hou Y, Zhu L, Li Z, Shen Q, Xu Q, Li W, Liu Y, Gong P..  (2019)  Design, synthesis and biological evaluation of novel 7-amino-[1,2,4]triazolo[4,3-f]pteridinone, and 7-aminotetrazolo[1,5-f]pteridinone derivative as potent antitumor agents.,  163  [PMID:30572179] [10.1016/j.ejmech.2018.12.009]

10. 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]

11. 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]

12. 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]

13. 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]

14. Li Z, Xu L, Zhu L, Zhao Y, Hu T, Yin B, Liu Y, Hou Y..  (2020)  Design, synthesis and biological evaluation of novel pteridinone derivatives possessing a hydrazone moiety as potent PLK1 inhibitors.,  30  (16): [PMID:32631534] [10.1016/j.bmcl.2020.127329]

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

16. Hengst JA,Hegde S,Paulson RF,Yun JK.  (2020)  Development of SKI-349, a dual-targeted inhibitor of sphingosine kinase and microtubule polymerization.,  30  (20.0): [PMID:32736077] [10.1016/j.bmcl.2020.127453]

17.  (2021)  EUbOPEN Chemogenomics Library wave 1,  [10.6019/CHEMBL4689842]

18. Deng Z,Chen G,Liu S,Li Y,Zhong J,Zhang B,Li L,Huang H,Wang Z,Xu Q,Deng X.  (2020)  Discovery of methyl 3-((2-((1-(dimethylglycyl)-5-methoxyindolin-6-yl)amino)-5-(trifluoro-methyl) pyrimidin-4-yl)amino)thiophene-2-carboxylate as a potent and selective polo-like kinase 1 (PLK1) inhibitor for combating hepatocellular carcinoma.,  206  [PMID:32814244] [10.1016/j.ejmech.2020.112697]

19. 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]

20. Karim RM, Bikowitz MJ, Chan A, Zhu JY, Grassie D, Becker A, Berndt N, Gunawan S, Lawrence NJ, Schönbrunn E..  (2021)  Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.,  64  (21.0): [PMID:34710325] [10.1021/acs.jmedchem.1c01096]

21. EUbOPEN.  (2022)  EUbOPEN Chemogenomics Library wave 2 - DSF,  [10.6019/CHEMBL5060014]

22. EUbOPEN.  (2023)  Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5209897]

23. EUbOPEN.  (2023)  Affinity Biochemical Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5210307]

24. EUbOPEN.  (2023)  Selectivity Literature for EUbOPEN Chemogenomics Library wave 3,  [10.6019/CHEMBL5212743]

25. Guler S, DiPoto MC, Crespo A, Caldwell R, Doerfel B, Grossmann N, Ho K, Huck B, Jones CC, Lan R, Musil D, Potnick J, Schilke H, Sherer B, Simon S, Sirrenberg C, Zhang Z, Liu-Bujalski L..  (2023)  Selective Wee1 Inhibitors Led to Antitumor Activity In Vitro and Correlated with Myelosuppression.,  14  (5): [PMID:37197456] [10.1021/acsmedchemlett.2c00481]

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

Source

Source(10):

• Scientific Literature
• Clinical Candidates
• USP Dictionary of USAN and International Drug Names
• Kuster lab chemical proteomics drug profiling
• SARS-CoV-2 Screening Data 2020-21
• EUbOPEN Chemogenomic Library
• IMI-CARE SARS-CoV-2 Data
• Fraunhofer HDAC6
• Literature data from EUbOPEN Chemogenomic Library
• EU-OPENSCREEN dataset