Detailed information for compound 311738
Basic information
Technical information
- TDR Targets ID: 311738
- Name: 4-[[4-[4-[(E)-2-cyanoethenyl]-2,6-dimethylani lino]pyrimidin-2-yl]amino]benzonitrile
- MW: 366.419 | Formula: C22H18N6
-
H donors: 2
H acceptors: 4
LogP: 4.55
Rotable bonds: 5
Rule of 5 violations (Lipinski): 1 - SMILES: N#C/C=C/c1cc(C)c(c(c1)C)Nc1ccnc(n1)Nc1ccc(cc1)C#N
- InChi: 1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+
- InChiKey: YIBOMRUWOWDFLG-ONEGZZNKSA-N
Network
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Synonyms
- 4-[[4-[4-[(E)-2-cyanovinyl]-2,6-dimethyl-anilino]pyrimidin-2-yl]amino]benzonitrile
- 4-[[4-[4-[(E)-2-cyanovinyl]-2,6-dimethylanilino]-2-pyrimidinyl]amino]benzonitrile
- 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzenecarbonitrile
- Rilpivirine
- 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]pyrimidin-2-yl]amino]benzonitrile
- 4-[[4-[[4-[(E)-2-cyanovinyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile
- 4-[[4-[[4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile
- 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethyl-phenyl]amino]pyrimidin-2-yl]amino]benzonitrile
- 500287-72-9
- 4-{4-[4-((E)-2-Cyano-vinyl)-2,6-dimethyl-phenylamino]-pyrimidin-2-ylamino}-benzonitrile
- AIDS-169030
- AIDS169030
- R278474
- TMC278
- Benzonitrile, 4-((4-((4-((1E)-2-cyanoethenyl)-2,6-dimethylphenyl)amino)-2-pyrimidinyl)amino)-
- R 278474
- Rilpivirine [INN]
- 4-((4-((4-((1E)-2-Cyanoethenyl)-2,6-dimethylphenyl)amino)-2-pyrimidinyl)amino)benzonitrile
- T27
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Human immunodeficiency virus 1 | Reverse transcriptase | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
| Species | Potential target | Known druggable target/s | Ortholog Group |
|---|---|---|---|
| Schistosoma mansoni | hypothetical protein | Get druggable targets OG5_139608 | All targets in OG5_139608 |
| Plasmodium yoelii | integrase-related | Get druggable targets OG5_139608 | All targets in OG5_139608 |
| Trypanosoma brucei | RNA helicase, putative | Get druggable targets OG5_139608 | All targets in OG5_139608 |
| Trypanosoma congolense | RNA helicase, putative | Get druggable targets OG5_139608 | All targets in OG5_139608 |
By sequence similarity to non orthologous known druggable targets
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Onchocerca volvulus | Matrix metalloproteinase homolog | 0.0441726 | 0.0987361 | 1 |
| Brugia malayi | Matrixin family protein | 0.0481551 | 0.114946 | 0.815985 |
| Echinococcus granulosus | DNA dependent protein kinase catalytic subunit | 0.265588 | 1 | 1 |
| Schistosoma mansoni | integrin alpha-ps | 0.0223638 | 0.00996379 | 0.0707312 |
| Mycobacterium leprae | PROBABLE HYDROLASE | 0.0242567 | 0.0176686 | 0.5 |
| Echinococcus granulosus | integrin alpha 3 | 0.0428794 | 0.0934719 | 0.0843485 |
| Onchocerca volvulus | Matrilysin homolog | 0.0441726 | 0.0987361 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0438035 | 0.0972335 | 0.38765 |
| Brugia malayi | Hemopexin family protein | 0.0282391 | 0.033879 | 0.240501 |
| Echinococcus multilocularis | integrin alpha 3 | 0.0428794 | 0.0934719 | 0.0843485 |
| Schistosoma mansoni | hypothetical protein | 0.0282391 | 0.033879 | 0.240501 |
| Echinococcus multilocularis | DNA dependent protein kinase catalytic subunit | 0.265588 | 1 | 1 |
| Schistosoma mansoni | integrin alpha | 0.0545233 | 0.140868 | 1 |
| Echinococcus granulosus | matrix metallopeptidase 7 M10 family | 0.0724117 | 0.213683 | 0.205769 |
| Loa Loa (eye worm) | matrixin family protein | 0.0481551 | 0.114946 | 0.458268 |
| Loa Loa (eye worm) | hypothetical protein | 0.0377338 | 0.0725271 | 0.289151 |
| Onchocerca volvulus | 0.0282391 | 0.033879 | 0.343127 | |
| Loa Loa (eye worm) | hypothetical protein | 0.0321595 | 0.049837 | 0.19869 |
| Loa Loa (eye worm) | hypothetical protein | 0.0242567 | 0.0176686 | 0.0704409 |
| Brugia malayi | Integrin alpha pat-2 precursor | 0.0545233 | 0.140868 | 1 |
| Leishmania major | hypothetical protein, conserved | 0.099383 | 0.323469 | 0.5 |
| Brugia malayi | Integrin alpha cytoplasmic region family protein | 0.0377338 | 0.0725271 | 0.514858 |
| Echinococcus multilocularis | matrix metallopeptidase 7 (M10 family) | 0.0724117 | 0.213683 | 0.205769 |
| Loa Loa (eye worm) | matrixin family protein | 0.0441726 | 0.0987361 | 0.39364 |
| Brugia malayi | Matrix metalloprotease, N-terminal domain containing protein | 0.0242567 | 0.0176686 | 0.125426 |
| Loa Loa (eye worm) | integrin alpha pat-2 | 0.0815373 | 0.250828 | 1 |
| Trypanosoma cruzi | hypothetical protein, conserved | 0.0965897 | 0.312098 | 0.5 |
| Mycobacterium ulcerans | hydrolase | 0.0242567 | 0.0176686 | 0.5 |
| Mycobacterium tuberculosis | Probable peptidoglycan hydrolase | 0.0242567 | 0.0176686 | 0.5 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (ADMET) | = 5.91 uM | Cytotoxicity against human MT4 cells by cell based assay | ChEMBL. | 19933797 |
| AUC (ADMET) | = 9650 ng.hr/ml | AUC in Wistar rat at 10 mg/kg, po | ChEMBL. | 17223230 |
| AUC (ADMET) | = 23790 ng.hr/ml | AUC in Beagle dog at 10 mg/kg, po | ChEMBL. | 17223230 |
| AUC (ADMET) | = 1.4 ug h/mL | Area under the concentration time curve of the compound in monkey(intravenous dosage of 1.25 mg/ kg) was determined | ChEMBL. | 15771434 |
| AUC (ADMET) | = 3.1 ug h/mL | Area under the concentration time curve value of the compound in rat(intravenous dosage of 4 mg/kg) was determined | ChEMBL. | 15771434 |
| AUC (ADMET) | = 8.7 ug h/mL | Area under the concentration time curve of the compound in dog(intravenous dosage of 1.25 mg/kg) was determined | ChEMBL. | 15771434 |
| AUC (ADMET) | = 44 ug h/mL | Area under the concentration time curve of the compound in rabbit(intravenous dosage of 1.25 mg/kg) was determined | ChEMBL. | 15771434 |
| AUC (ADMET) | = 9.8 ug hr-1 ml-1 | Area under the concentration time curve of the compound was determined in rat after 40 mg/kg oral dosage | ChEMBL. | 15771441 |
| CC50 (ADMET) | = 2000 nM | Cytotoxicity against human MT4 cells after 3 days by EGFP based replication assay | ChEMBL. | 17223230 |
| CC50 (ADMET) | = 2000 nM | Cytotoxicity against human MT4 cells after 3 days by EGFP based replication assay | ChEMBL. | 17223230 |
| CC50 (ADMET) | = 30000 nM | Cytotoxic concentration of the compound was determined against wild type human immunodeficiency virus type 1 LA1 strain | ChEMBL. | 15771449 |
| CC50 (ADMET) | > 1 uM | Cytotoxicity against human MT2 cells infected with HIV1 NL4.3 by MTT assay | ChEMBL. | 22081993 |
| CC50 (ADMET) | = 8 uM | Cytotoxicity against human MT4 cells infected with HIV1 NL4.3 by MTT assay | ChEMBL. | 22081993 |
| CC50 (ADMET) | = 8 uM | Cytotoxicity against human MT2 cells by MTT assay | ChEMBL. | 23899617 |
| CC50 (ADMET) | = 8 uM | Cytotoxicity against human MT2 cells assessed as reduction in cell viability by MTT assay | ChEMBL. | 25408842 |
| CC50 (ADMET) | = 8 uM | Cytotoxicity in human MT2 cells assessed as inhibition of cell growth | ChEMBL. | 23298809 |
| CC50 (ADMET) | = 8 uM | Cytotoxicity against human MT2 cells assessed as growth inhibition | ChEMBL. | 23937980 |
| CC50 (ADMET) | = 90.7 uM | Cytotoxicity against human MT2 cells assessed as cell viability | ChEMBL. | 25042339 |
| Cmax (ADMET) | = 1046 ng/ml | Cmax in Beagle dog at 10 mg/kg, po | ChEMBL. | 17223230 |
| Cmax (ADMET) | = 1940 ng/ml | Cmax in Wistar rat at 10 mg/kg, po | ChEMBL. | 17223230 |
| EC50 (functional) | = 0.1 nM | Effective concentration of the compound against human immunodeficiency virus type 1 G190S mutant strain | ChEMBL. | 15771434 |
| EC50 (functional) | = 0.1 nM | Antiviral activity against HIV1 LAI with RT K103N mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 0.3 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 103N | ChEMBL. | 15771449 |
| EC50 (functional) | = 0.3 nM | Effective concentration of the compound against human immunodeficiency virus type 1 K103N mutant strain | ChEMBL. | 15771434 |
| EC50 (functional) | = 0.4 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 100I | ChEMBL. | 15771449 |
| EC50 (functional) | = 0.4 nM | Effective concentration of the compound against rhuman immunodeficiency virus type 1 wild type mutant strain | ChEMBL. | 15771434 |
| EC50 (functional) | = 0.4 nM | Effective concentration of the compound against human immunodeficiency virus type 1 L100I mutant strain | ChEMBL. | 15771434 |
| EC50 (functional) | = 0.5 nM | Effective concentration of the compound was determined for the inhibition of wild type human immunodeficiency virus type 1 LAI strain | ChEMBL. | 15771449 |
| EC50 (functional) | = 0.5 nM | Antiviral activity against HIV1 LAI with RT L100I mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 0.5 nM | Antiviral activity against HIV1 LAI with RT F227C mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 0.5 nM | Antiviral activity against HIV1 LAI with RT F227C and V106A mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 1 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 227L+106A | ChEMBL. | 15771449 |
| EC50 (functional) | = 1 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 103N+181C | ChEMBL. | 15771449 |
| EC50 (functional) | = 1 nM | Effective concentration of the compound against human immunodeficiency virus type 1 K103N and Y181C mutant strains | ChEMBL. | 15771434 |
| EC50 (functional) | = 1 nM | Antiviral activity against wild type HIV1 LAI infected in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 1.2 nM | Antiviral activity against HIV1 LAI with RT Y188L mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 1.26 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 181C | ChEMBL. | 15771449 |
| EC50 (functional) | = 1.3 nM | Effective concentration of the compound against human immunodeficiency virus type 1 Y181C mutant strain | ChEMBL. | 15771434 |
| EC50 (functional) | = 1.3 nM | Antiviral activity against HIV1 LAI with RT Y181C mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 2 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 188L | ChEMBL. | 15771449 |
| EC50 (functional) | = 2 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 227C | ChEMBL. | 15771449 |
| EC50 (functional) | = 2 nM | Effective concentration of the compound against human immunodeficiency virus type 1 Y188L mutant strain | ChEMBL. | 15771434 |
| EC50 (functional) | = 3.2 nM | Antiviral activity against HIV1 LAI with RT K103N and Y181C mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 7.5 nM | Antiviral activity against HIV1 LAI with RT L100I and K103N mutation in MT4 cells by EGFP based replication assay | ChEMBL. | 17223230 |
| EC50 (functional) | = 7.95 nM | Effective concentration of the compound was determined against human immunodeficiency virus type 1 mutated at 100I+103N | ChEMBL. | 15771449 |
| IC50 (binding) | = 15 nM | Inhibition of wild-type HIV-1 reverse transcriptase by fluorescence assay | ChEMBL. | 26487915 |
| IC50 (binding) | = 42 nM | Inhibition of HIV1 Reverse transcriptase by primer extension-based scintillation assay | ChEMBL. | 19933797 |
| IC50 (functional) | = 1096 nM | Antimalarial activity against Plasmodium falciparum W2mef assessed as DNA positive erythrocytes by hoechst 33342-thiazole orange stain based flow cytometry assay | ChEMBL. | 19666223 |
| IC50 (functional) | = 1197 nM | Antimalarial activity against Plasmodium falciparum W2mef ring form by hoechst 33342-thiazole orange stain based flow cytometry assay | ChEMBL. | 19666223 |
| IC50 (functional) | = 1207 nM | Antimalarial activity against Plasmodium falciparum W2mef schizont form by hoechst 33342-thiazole orange stain based flow cytometry assay | ChEMBL. | 19666223 |
| IC50 (functional) | = 1998 nM | Antimalarial activity against Plasmodium falciparum W2mef trophozoite form by hoechst 33342-thiazole orange stain based flow cytometry assay | ChEMBL. | 19666223 |
| Inhibition (functional) | = 49.75 % | Antimalarial activity against Plasmodium falciparum W2mef at 10 uM after 48 hrs by hoechst 33342-thiazole orange stain based flow cytometry assay | ChEMBL. | 19666223 |
| pKa | = 5.6 | pKa value of the compound was determined | ChEMBL. | 15771441 |
| PPB (ADMET) | = 99.7 % | Plasma protein binding in human | ChEMBL. | 22071300 |
| Ratio CC50/EC50 (functional) | = 2020 | Selectivity index, ratio of CC50 for human MT4 cells to EC50 for HIV1 LAI | ChEMBL. | 17223230 |
| Selectivity index (functional) | = 60000 | Ratio of CC50 and EC50 of the compound against wild type human immunodeficiency virus type 1 LAI strain | ChEMBL. | 15771449 |
| Stabilty (ADMET) | = 26 % | Metabolic stability in human liver microsomes after 15 mins | ChEMBL. | 17223230 |
| Stabilty (ADMET) | = 65 % | Metabolic stability in dog liver microsomes after 15 mins | ChEMBL. | 17223230 |
| Stabilty (ADMET) | = 73 % | Metabolic stability in rat liver microsomes after 15 mins | ChEMBL. | 17223230 |
| Stabilty (ADMET) | = 80.2 % | Metabolic stability in human liver microsomes assessed as parent compound remaining at 1 uM incubated for 30 mins in presence of NADPH by LC-MS analysis | ChEMBL. | 27070547 |
| T1/2 (ADMET) | = 2 day | Half life in HIV-infected patient plasma | ChEMBL. | 22268494 |
| T1/2 (ADMET) | = 2.8 hr | Half life of the compound in rat was determined after oral administration | ChEMBL. | 15771434 |
| T1/2 (ADMET) | = 4.4 hr | Half life of the compound in rat was determined after intravenous administration | ChEMBL. | 15771434 |
| t1/2 (ADMET) | = 6 hr | Half life in Wistar rat at 10 mg/kg, po after 6 hrs | ChEMBL. | 17223230 |
| t1/2 (ADMET) | = 23 hr | Half life in Beagle dog at 10 mg/kg, po after 23 hrs | ChEMBL. | 17223230 |
| T1/2 (ADMET) | = 31 hr | Half life of the compound in dog was determined by intravenous administration | ChEMBL. | 15771434 |
| T1/2 (ADMET) | = 39 hr | In vivo half life of the compound in dog was determined after oral administration | ChEMBL. | 15771434 |
| TD50 (ADMET) | > 0.1 uM | Cytotoxicity against human MT4 assessed as cell viability after 2 days | ChEMBL. | 22818973 |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Plasmodium falciparum | ChEMBL23 | 19666223 |
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: CHEMBL175691
- PubChem: 6451164
Bibliographic References
4 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.