Detailed information for compound 163443
Basic information
Technical information
- TDR Targets ID: 163443
- Name: 2,3-dimethoxy-9-(trifluoromethyl)-7,12-dihydr o-5H-indolo[3,2-d][1]benzazepin-6-one
- MW: 376.329 | Formula: C19H15F3N2O3
-
H donors: 2
H acceptors: 1
LogP: 3.39
Rotable bonds: 3
Rule of 5 violations (Lipinski): 1 - SMILES: COc1cc2c(cc1OC)NC(=O)Cc1c2[nH]c2c1cc(cc2)C(F)(F)F
- InChi: 1S/C19H15F3N2O3/c1-26-15-6-12-14(8-16(15)27-2)23-17(25)7-11-10-5-9(19(20,21)22)3-4-13(10)24-18(11)12/h3-6,8,24H,7H2,1-2H3,(H,23,25)
- InChiKey: RVTOIQOTZUKDTE-UHFFFAOYSA-N
Network
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Synonyms
- Paullone Analog 9
- NSC702378
- NCI60_036667
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Homo sapiens | cyclin B3 | Starlite/ChEMBL | References |
| Homo sapiens | cyclin B2 | Starlite/ChEMBL | References |
| Homo sapiens | cyclin B1 | References | |
| Homo sapiens | cyclin-dependent kinase 5, regulatory subunit 1 (p35) | References | |
| Homo sapiens | cyclin-dependent kinase 3 | Starlite/ChEMBL | References |
| Homo sapiens | glycogen synthase kinase 3 beta | Starlite/ChEMBL | References |
| Homo sapiens | cyclin-dependent kinase 5 | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
By sequence similarity to non orthologous known druggable targets
| Species | Potential target | Known druggable target | Length | Alignment span | Identity |
|---|---|---|---|---|---|
| Trypanosoma brucei | mitogen-activated protein kinase 5 | cyclin-dependent kinase 3 | 305 aa | 303 aa | 32.0 % |
| Trypanosoma brucei | mitogen-activated protein kinase 5 | cyclin-dependent kinase 5 | 260 aa | 307 aa | 28.3 % |
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Trypanosoma cruzi | sedoheptulose-1,7-bisphosphatase, putative | 0.0192 | 0.2892 | 0.2116 |
| Trichomonas vaginalis | cyclin B, putative | 0.0124 | 0.1412 | 1 |
| Schistosoma mansoni | cyclin-dependent kinase 5 activator | 0.0309 | 0.547 | 0.5426 |
| Plasmodium vivax | protein kinase Crk2 | 0.0105 | 0.0984 | 0.5 |
| Echinococcus granulosus | cyclin dependent kinase 5 activator 1 | 0.0309 | 0.547 | 0.5426 |
| Loa Loa (eye worm) | CMGC/CDK/CDK5 protein kinase | 0.0105 | 0.0984 | 0.0984 |
| Loa Loa (eye worm) | CMGC/CDK/CDC2 protein kinase | 0.0105 | 0.0984 | 0.0984 |
| Echinococcus multilocularis | fructose 1,6 bisphosphatase 1 | 0.0515 | 1 | 1 |
| Schistosoma mansoni | cyclin B3 | 0.0199 | 0.3045 | 0.2979 |
| Trichomonas vaginalis | cyclin B, putative | 0.0124 | 0.1412 | 1 |
| Toxoplasma gondii | fructose-bisphospatase II | 0.0515 | 1 | 1 |
| Trypanosoma cruzi | cyclin, putative | 0.0124 | 0.1412 | 0.0475 |
| Trypanosoma cruzi | CYC2-like cyclin, putative | 0.0124 | 0.1412 | 0.0475 |
| Trichomonas vaginalis | cyclin B, putative | 0.0124 | 0.1412 | 1 |
| Giardia lamblia | Kinase, CMGC CDK | 0.0105 | 0.0984 | 0.6748 |
| Onchocerca volvulus | 0.0124 | 0.1412 | 0.5 | |
| Trichomonas vaginalis | cyclins, putative | 0.0075 | 0.0341 | 0.1865 |
| Entamoeba histolytica | cyclin, putative | 0.0124 | 0.1412 | 1 |
| Trypanosoma brucei | sedoheptulose-1,7-bisphosphatase | 0.0192 | 0.2892 | 0.2116 |
| Trypanosoma cruzi | fructose-1,6-bisphosphatase, cytosolic, putative | 0.0515 | 1 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0148 | 0.1932 | 0.1932 |
| Echinococcus granulosus | cyclin dependent kinase 5 | 0.0105 | 0.0984 | 0.0897 |
| Trypanosoma brucei | fructose-1,6-bisphosphatase | 0.0515 | 1 | 1 |
| Loa Loa (eye worm) | fructose-1,6-bisphosphatase | 0.0515 | 1 | 1 |
| Trichomonas vaginalis | CMGC family protein kinase | 0.0105 | 0.0984 | 0.6748 |
| Leishmania major | CYC2-like cyclin, putative,cyclin 6, putative | 0.0124 | 0.1412 | 0.0475 |
| Trichomonas vaginalis | CMGC family protein kinase | 0.0105 | 0.0984 | 0.6748 |
| Loa Loa (eye worm) | cyclin domain-containing protein | 0.0199 | 0.3045 | 0.3045 |
| Loa Loa (eye worm) | hypothetical protein | 0.0124 | 0.1412 | 0.1412 |
| Plasmodium falciparum | protein kinase 5 | 0.0105 | 0.0984 | 1 |
| Brugia malayi | Cyclin, N-terminal domain containing protein | 0.0199 | 0.3045 | 0.2286 |
| Brugia malayi | hypothetical protein | 0.0148 | 0.1932 | 0.1052 |
| Echinococcus multilocularis | cyclin dependent kinase 1 | 0.0105 | 0.0984 | 0.0897 |
| Echinococcus granulosus | 5'partial|cyclin dependent kinase 1 | 0.0105 | 0.0984 | 0.0897 |
| Trypanosoma brucei | mitotic cyclin 6 | 0.0124 | 0.1412 | 0.0475 |
| Trypanosoma cruzi | cyclin, putative | 0.0124 | 0.1412 | 0.0475 |
| Echinococcus multilocularis | cyclin dependent kinase 5 | 0.0105 | 0.0984 | 0.0897 |
| Loa Loa (eye worm) | hypothetical protein | 0.0103 | 0.0947 | 0.0947 |
| Giardia lamblia | Kinase, CMGC CDK | 0.0105 | 0.0984 | 0.6748 |
| Echinococcus granulosus | cyclin dependent kinase 1 | 0.0105 | 0.0984 | 0.0897 |
| Schistosoma mansoni | fructose-16-bisphosphatase-related | 0.0515 | 1 | 1 |
| Schistosoma mansoni | serine/threonine protein kinase | 0.0105 | 0.0984 | 0.0897 |
| Trypanosoma cruzi | sedoheptulose-1,7-bisphosphatase, putative | 0.0192 | 0.2892 | 0.2116 |
| Entamoeba histolytica | cell division protein kinase 2, putative | 0.0105 | 0.0984 | 0.6748 |
| Trichomonas vaginalis | cyclins, putative | 0.0124 | 0.1412 | 1 |
| Echinococcus multilocularis | cyclin B | 0.0124 | 0.1412 | 0.1329 |
| Echinococcus granulosus | G2:mitotic specific cyclin B3 | 0.0199 | 0.3045 | 0.2979 |
| Trichomonas vaginalis | cyclin A, putative | 0.0124 | 0.1412 | 1 |
| Trichomonas vaginalis | cyclins, putative | 0.0124 | 0.1412 | 1 |
| Trichomonas vaginalis | cyclins, putative | 0.0124 | 0.1412 | 1 |
| Echinococcus multilocularis | G2:mitotic specific cyclin B3 | 0.0199 | 0.3045 | 0.2979 |
| Echinococcus granulosus | cyclin dependent kinase | 0.0105 | 0.0984 | 0.0897 |
| Leishmania major | cyclin | 0.0124 | 0.1412 | 0.0475 |
| Leishmania major | 0.0515 | 1 | 1 | |
| Echinococcus granulosus | cyclin B | 0.0124 | 0.1412 | 0.1329 |
| Loa Loa (eye worm) | hypothetical protein | 0.0124 | 0.1412 | 0.1412 |
| Toxoplasma gondii | sedoheptulose-1,7-bisphosphatase | 0.0192 | 0.2892 | 0.2116 |
| Brugia malayi | Cyclin, N-terminal domain containing protein | 0.0124 | 0.1412 | 0.0475 |
| Brugia malayi | Cyclin, N-terminal domain containing protein | 0.0124 | 0.1412 | 0.0475 |
| Schistosoma mansoni | serine/threonine protein kinase | 0.0105 | 0.0984 | 0.0897 |
| Trichomonas vaginalis | CMGC family protein kinase | 0.0105 | 0.0984 | 0.6748 |
| Trypanosoma cruzi | cyclin 6, putative | 0.0124 | 0.1412 | 0.0475 |
| Entamoeba histolytica | cell division protein kinase 2, putative | 0.0105 | 0.0984 | 0.6748 |
| Loa Loa (eye worm) | CMGC/CDK/CDC2 protein kinase | 0.0105 | 0.0984 | 0.0984 |
| Echinococcus granulosus | fructose 16 bisphosphatase 1 | 0.0515 | 1 | 1 |
| Echinococcus multilocularis | cyclin dependent kinase 1 | 0.0105 | 0.0984 | 0.0897 |
| Trichomonas vaginalis | cyclins, putative | 0.0124 | 0.1412 | 1 |
| Toxoplasma gondii | fructose-bisphospatase I | 0.0192 | 0.2892 | 0.2116 |
| Schistosoma mansoni | cyclin B | 0.0124 | 0.1412 | 0.1329 |
| Trichomonas vaginalis | cyclin B, putative | 0.0124 | 0.1412 | 1 |
| Trypanosoma cruzi | fructose-1,6-bisphosphatase, cytosolic, putative | 0.0515 | 1 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0148 | 0.1932 | 0.1932 |
| Loa Loa (eye worm) | hypothetical protein | 0.0309 | 0.547 | 0.547 |
| Echinococcus multilocularis | cyclin dependent kinase | 0.0105 | 0.0984 | 0.0897 |
| Echinococcus multilocularis | cyclin dependent kinase 5 activator 1 | 0.0309 | 0.547 | 0.5426 |
| Giardia lamblia | G2/mitotic-specific cyclin B | 0.0124 | 0.1412 | 1 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (binding) | = 97.7 % | Inhibition of mitochondrial malate dehydrogenase assessed as residual enzyme activity at 10 uM by spectrophotometry | ChEMBL. | 19906467 |
| GI50 (functional) | = -5.7 | The logarithmic molar concentration inhibiting 50% net cell growth was measured on HCT-116(M) colon cancer cell lines. | ChEMBL. | 10425100 |
| GI50 (functional) | -5.587 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the HL-60(TB) Leukemia cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.536 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the UO-31 Renal cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.472 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the MDA-N Breast cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.464 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the ACHN Renal cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.44 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the SK-MEL-5 Melanoma cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.393 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the SF-539 Central Nervous System cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.338 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the DU-145 Prostate cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.208 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the NCI-H23 Non-Small Cell Lung cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -5.005 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the SN12C Renal cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| GI50 (functional) | -4.882 | PUBCHEM_BIOASSAY: NCI human tumor cell line growth inhibition assay. Data for the MALME-3M Melanoma cell line. (Class of assay: confirmatory) | ChEMBL. | No reference |
| IC50 (binding) | = 6.367 | Inhibitory activity against cyclin-dependent kinase 5/p25 | ChEMBL. | 14695817 |
| IC50 (binding) | = 6.553 | Inhibitory activity against cyclin dependent kinase 1-cyclinB extracted from M phase starfish (Marthasterias glacialis) oocytes | ChEMBL. | 14695817 |
| IC50 (binding) | = 7.125 | Inhibitory activity against glycogen synthase kinase-3 beta purified from insect sf9 cells | ChEMBL. | 14695817 |
| IC50 (binding) | = 0.075 microM | Inhibition of GSK3-beta | ChEMBL. | 19906467 |
| IC50 (binding) | = 0.28 microM | Inhibition of CDK1/cyclin B | ChEMBL. | 19906467 |
| IC50 (binding) | = 0.28 uM | In vitro inhibitory activity against cyclin-dependent kinase 1-cyclin B (Cyclin-Dependent Kinase) harvested from starfish oocytes. | ChEMBL. | 10425100 |
| IC50 (binding) | = 0.28 uM | In vitro inhibitory activity against cyclin-dependent kinase 1-cyclin B (Cyclin-Dependent Kinase) harvested from starfish oocytes. | ChEMBL. | 10425100 |
| Log GI50 (functional) | = -5.7 | The logarithmic molar concentration inhibiting 50% net cell growth was measured on HCT-116(M) colon cancer cell lines. | ChEMBL. | 10425100 |
| Log GI50 (functional) | = -5.3 | Antitumor activity of the compound was reported for each out of 60 human tumor cell lines (experiment 2) | ChEMBL. | 10425100 |
| Log GI50 (functional) | = -5.2 | Antitumor activity of the compound was reported for each out of 60 human tumor cell lines (experiment 1) | ChEMBL. | 10425100 |
| Log IC50 (binding) | = 6.367 | Inhibitory activity against cyclin-dependent kinase 5/p25 | ChEMBL. | 14695817 |
| Log IC50 (binding) | = 6.553 | Inhibitory activity against cyclin dependent kinase 1-cyclinB extracted from M phase starfish (Marthasterias glacialis) oocytes | ChEMBL. | 14695817 |
| Log IC50 (binding) | = 7.12499999999999 | Inhibitory activity against glycogen synthase kinase-3 beta purified from insect sf9 cells | ChEMBL. | 14695817 |
Phenotypes
Whole-cell/tissue/organism interactions
We have no records of whole-cell/tissue assays done with this compound
What does this mean?
Many chemical entities in TDR Targets come from high-throughput screenings with whole cells or tissue samples, and not all assayed compounds have been tested against a single a single target protein, probably because they get ruled out during screening process. Even if these compounds may have not been of interest in the original screening, they may come as interesting leads for other screening assays. Furthermore, we may be able to propose drug-target associations using chemical similarities and network patterns.
Annotated phenotypes:
We have no manually annotated phenotypes for this drug.
What does this mean? / Care to help?
In TDR Targets, information about phenotypes that are caused by
drugs, or by genetic manipulation of cells (e.g. gene knockouts or
knockdowns) is manually curated from the literature. These
descriptions help to describe the potential of the target for drug
development. If no information is available for this gene or if the
information is incomplete, this may mean that i) the papers
containing this information either appeared after the curation
effort for this organism was carried out or they were inadvertently
missed by curators; or that ii) the curation effort for this
organism has not yet started.
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.
In any case, if you have information about papers containing relevant validation data for this target, please log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.
External resources for this compound
- ChEMBL: CHEMBL328194
- PubChem: 396412
Bibliographic References
3 literature references were collected for this gene.
If you have references for this compound, please enter them in a user comment (below) or Contact us.