TDR Targets

Basic information

Technical information

TDR Targets ID: 186947
Name: 5-(4-amino-5,8-difluorospiro[1H-quinazoline-2 ,4'-piperidine]-1'-carbonyl)pyridine-2-carbon itrile
MW: 382.367 | Formula: C19H16F2N6O
H donors: 2 H acceptors: 3 LogP: 1.25 Rotable bonds: 2
Rule of 5 violations (Lipinski): 1
SMILES: N#Cc1ccc(cn1)C(=O)N1CCC2(CC1)N=C(N)c1c(N2)c(F)ccc1F
InChi: 1S/C19H16F2N6O/c20-13-3-4-14(21)16-15(13)17(23)26-19(25-16)5-7-27(8-6-19)18(28)11-1-2-12(9-22)24-10-11/h1-4,10,25H,5-8H2,(H2,23,26)
InChiKey: GIZYIOOBBUHOBS-UHFFFAOYSA-N

Network

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Target Layer

Model Organisms

Species	Viewmode
Arabidopsis thaliana
Caenorhabditis elegans
Dictyostelium discoideum
Drosophila melanogaster
Escherichia coli
Homo sapiens
Mus musculus
Oryza sativa
Saccharomyces cerevisiae
Schmidtea mediterranea
Other organisms

TDR Pathogens:

Species	Viewmode
Brugia malayi
Chlamydia trachomatis
Echinococcus granulosus
Entamoeba histolytica
Echinococcus multilocularis
Giardia lamblia
Leishmania major
Loa Loa (eye worm)
Mycobacterium leprae
Mycobacterium tuberculosis
Mycobacterium ulcerans
Onchocerca volvulus
Plasmodium falciparum
Plasmodium vivax
Schistosoma mansoni
Trypanosoma brucei
Trypanosoma cruzi
Toxoplasma gondii
Treponema pallidum
Trichomonas vaginalis
Wolbachia endosymbiont of Brugia malayi

Other Pathogens:

Species	Viewmode
Babesia bovis
Candida albicans
Cryptosporidium hominis
Cryptosporidium parvum
Leishmania braziliensis
Leishmania donovani
Leishmania infantum
Leishmania mexicana
Neospora caninum
Plasmodium berghei
Plasmodium knowlesi
Plasmodium yoelii
Schistosoma japonicum
Trypanosoma brucei gambiense
Trypanosoma congolense
Theileria parva

Compound Layer

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Clustering layers

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Synonyms

5-(4-amino-5,8-difluoro-spiro[1H-quinazoline-2,4'-piperidine]-1'-carbonyl)pyridine-2-carbonitrile
5-[(4-amino-5,8-difluoro-1'-spiro[1H-quinazoline-2,4'-piperidine]yl)-oxomethyl]-2-pyridinecarbonitrile
5-(4-azanyl-5,8-difluoro-spiro[1H-quinazoline-2,4'-piperidine]-1'-yl)carbonylpyridine-2-carbonitrile
5-(4-amino-5,8-difluoro-spiro[1H-quinazoline-2,4'-piperidine]-1'-carbonyl)picolinonitrile
5-(4-amino-5,8-difluoro-spiro[1H-quinazoline-2,4'-piperidine]-1'-yl)carbonylpyridine-2-carbonitrile

Targets

Known targets for this compound

Species	Target name	Source	Bibliographic reference
Homo sapiens	nitric oxide synthase 2, inducible	Starlite/ChEMBL	References
Homo sapiens	nitric oxide synthase 1 (neuronal)	Starlite/ChEMBL	References
Homo sapiens	potassium voltage-gated channel, subfamily H (eag-related), member 2	Starlite/ChEMBL	References

Predicted pathogen targets for this compound

By orthology

Species	Potential target	Known druggable target/s	Ortholog Group
Schistosoma mansoni	voltage-gated potassium channel	Get druggable targets OG5_128858	All targets in OG5_128858
Loa Loa (eye worm)	voltage and ligand gated potassium channel	Get druggable targets OG5_128858	All targets in OG5_128858
Echinococcus granulosus	potassium voltage gated channel subfamily H	Get druggable targets OG5_128858	All targets in OG5_128858
Loa Loa (eye worm)	hypothetical protein	Get druggable targets OG5_128858	All targets in OG5_128858
Schistosoma japonicum	ko:K04910 potassium voltage-gated channel, Eag-related subfamily H, member 7, putative	Get druggable targets OG5_128858	All targets in OG5_128858
Trichomonas vaginalis	voltage and ligand gated potassium channel, putative	Get druggable targets OG5_128858	All targets in OG5_128858
Schistosoma japonicum	Potassium voltage-gated channel subfamily H member 2, putative	Get druggable targets OG5_128858	All targets in OG5_128858
Schistosoma japonicum	ko:K04910 potassium voltage-gated channel, Eag-related subfamily H, member 7, putative	Get druggable targets OG5_128858	All targets in OG5_128858
Brugia malayi	Voltage-gated potassium channel, HERG (KCNH2)-related. C. elegans unc-103 ortholog	Get druggable targets OG5_128858	All targets in OG5_128858
Schistosoma mansoni	voltage-gated potassium channel	Get druggable targets OG5_128858	All targets in OG5_128858
Trichomonas vaginalis	voltage and ligand gated potassium channel, putative	Get druggable targets OG5_128858	All targets in OG5_128858
Echinococcus multilocularis	potassium voltage gated channel subfamily H	Get druggable targets OG5_128858	All targets in OG5_128858

By sequence similarity to non orthologous known druggable targets

No druggable targets predicted by sequence similarity

Ranking Plot

Putative Targets List

Species	Potential target	Raw	Global	Species
Mycobacterium tuberculosis	Probable isocitrate dehydrogenase [NADP] Icd1 (oxalosuccinate decarboxylase) (IDH) (NADP+-specific ICDH) (IDP)	0.0333	1	1
Echinococcus granulosus	potassium voltage gated channel subfamily H	0.0013	0.0126	0.0126
Trypanosoma brucei	NADPH-cytochrome p450 reductase, putative	0.0059	0.1554	0.1178
Echinococcus granulosus	potassium voltage gated channel subfamily H	0.0045	0.1103	0.1103
Echinococcus multilocularis	methionine synthase reductase	0.0037	0.0856	0.0856
Echinococcus multilocularis	isocitrate dehydrogenase (NAD+)	0.004	0.0976	0.0976
Trypanosoma cruzi	cytochrome P450 reductase, putative	0.0059	0.1554	0.1178
Brugia malayi	flavodoxin family protein	0.0023	0.0426	0.0426
Echinococcus multilocularis	potassium voltage gated channel subfamily H	0.0045	0.1103	0.1103
Mycobacterium ulcerans	formate dehydrogenase H FdhF	0.0059	0.1554	1
Echinococcus granulosus	NADP dependent isocitrate dehydrogenase	0.0333	1	1
Leishmania major	isocitrate dehydrogenase, putative	0.004	0.0976	0.0574
Brugia malayi	Voltage-gated potassium channel, HERG (KCNH2)-related. C. elegans unc-103 ortholog	0.0045	0.1103	0.1103
Giardia lamblia	Hypothetical protein	0.0052	0.1346	0.5
Toxoplasma gondii	isocitrate dehydrogenase	0.0333	1	1
Plasmodium falciparum	nitric oxide synthase, putative	0.0059	0.1554	0.1178
Schistosoma mansoni	voltage-gated potassium channel	0.0049	0.1229	0.1229
Schistosoma mansoni	diflavin oxidoreductase	0.0029	0.0634	0.0634
Schistosoma mansoni	unc-13 (munc13)	0.004	0.0976	0.0976
Echinococcus granulosus	methionine synthase reductase	0.0037	0.0856	0.0856
Schistosoma mansoni	cytochrome P450 reductase	0.0059	0.1554	0.1554
Trichomonas vaginalis	NADPH cytochrome P450, putative	0.0023	0.0426	0.2744
Schistosoma mansoni	voltage-gated potassium channel	0.0049	0.1229	0.1229
Brugia malayi	Isocitrate dehydrogenase	0.0333	1	1
Trypanosoma brucei	isocitrate dehydrogenase, putative	0.0333	1	1
Giardia lamblia	Nitric oxide synthase, inducible	0.0052	0.1346	0.5
Echinococcus granulosus	isocitrate dehydrogenase NAD subunit	0.004	0.0976	0.0976
Schistosoma mansoni	Isocitrate dehydrogenase [NAD] subunit gamma mitochondrial	0.004	0.0976	0.0976
Brugia malayi	Isocitrate dehydrogenase subunit gamma, mitochondrial precursor	0.004	0.0976	0.0976
Loa Loa (eye worm)	isocitrate dehydrogenase	0.0333	1	1
Trypanosoma cruzi	NADPH-dependent FMN/FAD containing oxidoreductase, putative	0.0059	0.1554	0.1178
Schistosoma mansoni	voltage-gated potassium channel	0.0013	0.0126	0.0126
Leishmania major	p450 reductase, putative	0.0059	0.1554	0.1178
Schistosoma mansoni	isocitrate dehydrogenase	0.004	0.0976	0.0976
Loa Loa (eye worm)	hypothetical protein	0.004	0.0976	0.0976
Plasmodium vivax	flavodoxin domain containing protein	0.0052	0.1346	0.0961
Echinococcus granulosus	isocitrate dehydrogenase NAD	0.004	0.0976	0.0976
Brugia malayi	isocitrate dehydrogenase [NAD] subunit beta, mitochondrial	0.004	0.0976	0.0976
Trypanosoma cruzi	p450 reductase, putative	0.0059	0.1554	0.1178
Brugia malayi	FAD binding domain containing protein	0.0037	0.0856	0.0856
Echinococcus granulosus	NADPH dependent diflavin oxidoreductase 1	0.0059	0.1554	0.1554
Schistosoma mansoni	5-methyl tetrahydrofolate-homocysteine methyltransferase reductase	0.0037	0.0856	0.0856
Leishmania major	NADPH-cytochrome p450 reductase-like protein	0.0059	0.1554	0.1178
Wolbachia endosymbiont of Brugia malayi	isocitrate dehydrogenase	0.004	0.0976	0.5
Loa Loa (eye worm)	hypothetical protein	0.0039	0.0921	0.0921
Mycobacterium leprae	PROBABLE 3-ISOPROPYLMALATE DEHYDROGENASE LEUB (BETA-IPM DEHYDROGENASE) (IMDH) (3-IPM-DH)	0.004	0.0976	0.5
Trypanosoma brucei	isocitrate dehydrogenase [NADP], mitochondrial precursor, putative	0.0333	1	1
Plasmodium vivax	isocitrate dehydrogenase [NADP], mitochondrial, putative	0.0333	1	1
Loa Loa (eye worm)	FAD binding domain-containing protein	0.0037	0.0856	0.0856
Echinococcus multilocularis	isocitrate dehydrogenase (NAD) subunit	0.004	0.0976	0.0976
Echinococcus multilocularis	isocitrate dehydrogenase	0.0333	1	1
Loa Loa (eye worm)	FAD binding domain-containing protein	0.0059	0.1554	0.1554
Echinococcus granulosus	NADPH cytochrome P450 reductase	0.0059	0.1554	0.1554
Schistosoma mansoni	voltage-gated potassium channel	0.0013	0.0126	0.0126
Brugia malayi	isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial	0.004	0.0976	0.0976
Plasmodium vivax	NADPH-cytochrome p450 reductase, putative	0.0059	0.1554	0.1178
Echinococcus multilocularis	voltage gated potassium channel	0.0013	0.0126	0.0126
Entamoeba histolytica	tartrate dehydrogenase, putative	0.004	0.0976	1
Trypanosoma cruzi	isocitrate dehydrogenase, putative	0.0333	1	1
Brugia malayi	Probable isocitrate dehydrogenase	0.004	0.0976	0.0976
Trypanosoma brucei	NADPH--cytochrome P450 reductase, putative	0.0059	0.1554	0.1178
Trichomonas vaginalis	NADPH cytochrome P450, putative	0.0023	0.0426	0.2744
Loa Loa (eye worm)	flavodoxin family protein	0.0023	0.0426	0.0426
Echinococcus multilocularis	NADPH cytochrome P450 reductase	0.0059	0.1554	0.1554
Echinococcus multilocularis	isocitrate dehydrogenase 2 (NADP+)	0.0333	1	1
Loa Loa (eye worm)	hypothetical protein	0.0059	0.1554	0.1554
Loa Loa (eye worm)	voltage and ligand gated potassium channel	0.0045	0.1103	0.1103
Echinococcus multilocularis	NADPH dependent diflavin oxidoreductase 1	0.0059	0.1554	0.1554
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.0333	1	1
Trypanosoma brucei	NADPH--cytochrome P450 reductase, putative	0.0059	0.1554	0.1178
Trichomonas vaginalis	sulfite reductase, putative	0.0059	0.1554	1
Trypanosoma cruzi	cytochrome P450 reductase, putative	0.0059	0.1554	0.1178
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.0333	1	1
Leishmania major	isocitrate dehydrogenase [NADP], mitochondrial precursor, putative	0.0333	1	1
Trichomonas vaginalis	isocitrate dehydrogenase, putative	0.004	0.0976	0.6279
Chlamydia trachomatis	sulfite reductase	0.0037	0.0856	0.5
Trichomonas vaginalis	voltage and ligand gated potassium channel, putative	0.0042	0.1012	0.6513
Schistosoma mansoni	NADPH flavin oxidoreductase	0.003	0.0648	0.0648
Leishmania major	cytochrome P450 reductase, putative	0.0052	0.1346	0.0961
Brugia malayi	flavodoxin family protein	0.0059	0.1554	0.1554
Loa Loa (eye worm)	isocitrate dehydrogenase gamma subunit	0.004	0.0976	0.0976
Echinococcus multilocularis	potassium voltage gated channel subfamily H	0.0013	0.0126	0.0126
Brugia malayi	FAD binding domain containing protein	0.0059	0.1554	0.1554
Trichomonas vaginalis	NADPH fad oxidoreductase, putative	0.0052	0.1346	0.8664
Trypanosoma brucei	NADPH-dependent diflavin oxidoreductase 1	0.0059	0.1554	0.1178
Treponema pallidum	flavodoxin	0.0023	0.0426	0.5
Brugia malayi	Voltage-gated potassium channel, EAG (KCNH1)-related. C. elegans egl-2 ortholog	0.0013	0.0126	0.0126
Echinococcus multilocularis	NADP dependent isocitrate dehydrogenase	0.0333	1	1
Schistosoma mansoni	NADP-specific isocitrate dehydrogenase	0.0333	1	1
Trichomonas vaginalis	NADPH cytochrome P450, putative	0.0023	0.0426	0.2744
Brugia malayi	Probable isocitrate dehydrogenase	0.004	0.0976	0.0976
Trichomonas vaginalis	voltage and ligand gated potassium channel, putative	0.0042	0.1012	0.6513
Trypanosoma cruzi	isocitrate dehydrogenase [NADP], mitochondrial precursor, putative	0.0333	1	1
Trichomonas vaginalis	NADPH cytochrome P450, putative	0.0023	0.0426	0.2744
Loa Loa (eye worm)	hypothetical protein	0.0013	0.0126	0.0126
Toxoplasma gondii	isocitrate dehydrogenase	0.0333	1	1
Echinococcus granulosus	voltage gated potassium channel	0.0013	0.0126	0.0126
Plasmodium falciparum	isocitrate dehydrogenase [NADP], mitochondrial	0.0333	1	1

Activities

Activity type	Activity value	Assay description	Source	Reference
ED50 (functional)	~ 10 uM kg-1	Effective dose of compound against acute andchronic models of inflammatory arthritis	ChEMBL.	12620067
IC50 (binding)		Inhibition of serotonin transporter	ChEMBL.	21398123
IC50 (ADMET)		Inhibition of CYP2D6	ChEMBL.	21398123
IC50 (binding)		Inhibition of NET	ChEMBL.	21398123
IC50 (binding)	> 4	Inhibition of human eNOS assessed as inhibition of [3H]L-arginine to [3H]L-citrulline conversion by scintillation counting	ChEMBL.	21684157
IC50 (binding)	= 6.13	Inhibition of human nNOS assessed as inhibition of [3H]L-arginine to [3H]L-citrulline conversion by scintillation counting	ChEMBL.	21684157
IC50 (binding)	= 7.43	Inhibition of human iNOS assessed as inhibition of [3H]L-arginine to [3H]L-citrulline conversion by scintillation counting	ChEMBL.	21684157
IC50 (binding)	= 170 nM	Inhibition of human iNOS expressed in human DLD1 cells after 1 hr	ChEMBL.	18024030
IC50 (binding)	= 170 nM	Inhibition of human iNOS expressed in human DLD1 cells after 1 hr	ChEMBL.	18024030
IC50 (binding)	= 210 nM	Inhibition of cytokine-induced iNOS activity in human DLD1 cells after 24 hrs	ChEMBL.	18024030
IC50 (binding)	= 210 nM	Inhibition of cytokine-induced iNOS activity in human DLD1 cells after 24 hrs	ChEMBL.	18024030
IC50 (binding)	= 840 nM	Inhibition of human nNOS expressed in insect SF9 cells after 1 hr	ChEMBL.	18024030
IC50 (binding)	= 840 nM	Inhibition of human nNOS expressed in insect SF9 cells after 1 hr	ChEMBL.	18024030
IC50 (binding)	= 0.035 uM	Inhibition of human iNOS	ChEMBL.	18849972
IC50 (binding)	= 0.037 uM	In vitro inhibition of human Inducible nitric oxide synthase.	ChEMBL.	15163211
IC50 (binding)	= 0.037 uM	Inhibitory activity of compound against human inducible nitiric oxide synthase	ChEMBL.	12620067
IC50 (binding)	= 0.037 uM	In vitro inhibition of human Inducible nitric oxide synthase.	ChEMBL.	15163211
IC50 (binding)	= 0.037 uM	Inhibitory activity of compound against human inducible nitiric oxide synthase	ChEMBL.	12620067
IC50 (binding)	= 0.041 uM	Inhibition of human recombinant iNOS	ChEMBL.	21398123
IC50 (binding)	= 0.1 uM	Inhibition of human ERG	ChEMBL.	21398123
IC50 (binding)	= 0.74 uM	In vitro inhibition of human neuronal nitric oxide synthase.	ChEMBL.	15163211
IC50 (binding)	= 0.74 uM	In vitro inhibition of human neuronal nitric oxide synthase.	ChEMBL.	15163211
IC50 (binding)	= 0.79 uM	Inhibition of human nNOS	ChEMBL.	18849972
IC50 (functional)	= 0.9 uM	Inhibitory activity against synthesis of inducible nitiric oxide synthase by DLD-1 cells	ChEMBL.	12620067
IC50 (binding)	= 0.9 uM	Inhibition of human iNOS by whole cell assay	ChEMBL.	18849972
IC50 (functional)	= 0.9 uM	Inhibitory activity against synthesis of inducible nitiric oxide synthase by DLD-1 cells	ChEMBL.	12620067
IC50 (binding)	= 1 uM	Inhibitory activity against human neuronal nitiric oxide synthase	ChEMBL.	12620067
IC50 (binding)	= 1 uM	Inhibitory activity against human neuronal nitiric oxide synthase	ChEMBL.	12620067
IC50 (binding)	= 1 uM	Inhibition of iNOS in intact human DLD1 cells assessed as nitric oxide production	ChEMBL.	21398123
IC50 (binding)	> 100 uM	In vitro inhibition of human endothelial nitric oxide synthase.	ChEMBL.	15163211
IC50 (binding)	> 100 uM	In vitro inhibition of human endothelial nitric oxide synthase.	ChEMBL.	15163211
IC50 (binding)	> 100 uM	Inhibition of human eNOS	ChEMBL.	18849972
ID50 (functional)	= 3 uM kg-1	Inhibition of LPS induced nitrite production in rat following 4 hr of oral administration	ChEMBL.	12620067
Inhibition (binding)	< 15 %	Inhibition of human eNOS expressed in insect SF9 cells at 10 uM after 1 hr	ChEMBL.	18024030
Inhibition (binding)	< 15 %	Inhibition of human eNOS expressed in insect SF9 cells at 10 uM after 1 hr	ChEMBL.	18024030
Inhibition (binding)	< 20 %	Percentage inhibition of human endothelial nitric oxide synthase (eNOS) at 100 uM	ChEMBL.	15163211
Inhibition (binding)	< 20 %	Percentage inhibition of human endothelial nitric oxide synthase (eNOS) at 100 uM	ChEMBL.	15163211
Inhibition (binding)	= 50 %	Inhibitory activity of 100 uM compound against human endothelial nitiric oxide synthase; Range is 25%-50%	ChEMBL.	12620067
Inhibition (binding)	= 50 %	Inhibitory activity of 100 uM compound against human endothelial nitiric oxide synthase; Range is 25%-50%	ChEMBL.	12620067
Ratio IC50 (binding)	= 5	Selectivity for human nNOS to human iNOS	ChEMBL.	18024030
Ratio IC50 (binding)	> 70	Selectivity for human eNOS to human iNOS	ChEMBL.	18024030
Stability (ADMET)	< 3 uL/min	Metabolic stability in human hepatocytes assessed as per 10'6 cells	ChEMBL.	21398123

Phenotypes

Whole-cell/tissue/organism interactions

Species name	Source	Reference	Is orphan
Homo sapiens	ChEMBL23	12620067

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.

External resources for this compound

ChEMBL: CHEMBL447183
PubChem: 9886249

Bibliographic References

6 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.

Detailed information for compound 186947