TDR Targets

Basic information

Technical information

TDR Targets ID: 302058
Name: 8-methyl-7-(2-methylbutan-2-yl)pyrrolo[3,2-f] quinazoline-1,3-diamine
MW: 283.371 | Formula: C16H21N5
H donors: 2 H acceptors: 2 LogP: 2.74 Rotable bonds: 2
Rule of 5 violations (Lipinski): 1
SMILES: CCC(n1c(C)cc2c1ccc1c2c(N)nc(n1)N)(C)C
InChi: 1S/C16H21N5/c1-5-16(3,4)21-9(2)8-10-12(21)7-6-11-13(10)14(17)20-15(18)19-11/h6-8H,5H2,1-4H3,(H4,17,18,19,20)
InChiKey: HVCRYOZBFZLNFW-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

7-(1,1-dimethylpropyl)-8-methyl-pyrrolo[3,2-f]quinazoline-1,3-diamine
7-(1,1-dimethylpropyl)-8-methylpyrrolo[3,2-f]quinazoline-1,3-diamine
(1-amino-7-tert-amyl-8-methyl-pyrrolo[3,2-f]quinazolin-3-yl)amine
(3-amino-7-tert-amyl-8-methyl-pyrrolo[3,2-f]quinazolin-1-yl)amine
AIDS-057265
AIDS057265
3-(1,1-Dimethylpropyl)-2-methylpyrrolo[3,2-f]quinazoline-7,9-diamine

Targets

Known targets for this compound

Species	Target name	Source	Bibliographic reference
Homo sapiens	dihydrofolate reductase	Starlite/ChEMBL	References
Candida albicans	dihydrofolate reductase	Starlite/ChEMBL	References

Predicted pathogen targets for this compound

By orthology

Species	Potential target	Known druggable target/s	Ortholog Group
Brugia malayi	Dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Mycobacterium leprae	DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE)	Get druggable targets OG5_128410	All targets in OG5_128410
Chlamydia trachomatis	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Echinococcus granulosus	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Brugia malayi	dihydrofolate reductase family protein	Get druggable targets OG5_128410	All targets in OG5_128410
Schistosoma japonicum	ko:K00287 dihydrofolate reductase [EC1.5.1.3], putative	Get druggable targets OG5_128410	All targets in OG5_128410
Mycobacterium ulcerans	dihydrofolate reductase DfrA	Get druggable targets OG5_128410	All targets in OG5_128410
Candida albicans	hypothetical protein	Get druggable targets OG5_128410	All targets in OG5_128410
Loa Loa (eye worm)	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Echinococcus multilocularis	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Schistosoma mansoni	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Candida albicans	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Candida albicans	dihydrofolate reductase	Get druggable targets OG5_128410	All targets in OG5_128410
Mycobacterium tuberculosis	Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase)	Get druggable targets OG5_128410	All targets in OG5_128410

By sequence similarity to non orthologous known druggable targets

Species	Potential target	Known druggable target	Length	Alignment span	Identity
Plasmodium falciparum	bifunctional dihydrofolate reductase-thymidylate synthase	dihydrofolate reductase	187 aa	202 aa	29.7 %

Ranking Plot

Putative Targets List

Species	Potential target	Raw	Global	Species
Schistosoma mansoni	hypothetical protein	0.0177	0.1254	0.394
Echinococcus granulosus	histone deacetylase 3	0.0063	0.0333	0.1001
Toxoplasma gondii	inositol(myo)-1(or 4)-monophosphatase 2, putative	0.0038	0.0137	0.0385
Schistosoma mansoni	P2X receptor subunit	0.0071	0.0398	0.1251
Trypanosoma cruzi	telomerase reverse transcriptase, putative	0.0344	0.2605	1
Loa Loa (eye worm)	hypothetical protein	0.0042	0.0169	0.0532
Toxoplasma gondii	histone deacetylase HDAC3	0.0063	0.0333	0.1148
Plasmodium falciparum	bifunctional dihydrofolate reductase-thymidylate synthase	0.0159	0.111	0.4174
Echinococcus multilocularis	histone deacetylase 1	0.0063	0.0333	0.1001
Schistosoma mansoni	tar DNA-binding protein	0.0066	0.036	0.1131
Brugia malayi	Bromodomain containing protein	0.0078	0.0458	0.0588
Brugia malayi	Bromodomain containing protein	0.004	0.0149	0.0157
Plasmodium vivax	histone deacetylase 1, putative	0.0063	0.0333	0.1148
Trypanosoma cruzi	histone deacetylase 1, putative	0.0063	0.0333	0.1148
Loa Loa (eye worm)	hypothetical protein	0.0026	0.0039	0.0121
Echinococcus granulosus	p2X purinoceptor 4	0.0071	0.0398	0.1206
Echinococcus granulosus	p2X purinoceptor 4	0.0071	0.0398	0.1206
Trypanosoma cruzi	telomerase reverse transcriptase, putative	0.0344	0.2605	1
Brugia malayi	TAR-binding protein	0.0066	0.036	0.0451
Schistosoma mansoni	inositol monophosphatase	0.0038	0.0137	0.0432
Trypanosoma brucei	histone deacetylase 1	0.0063	0.0333	0.1148
Loa Loa (eye worm)	RNA binding protein	0.0066	0.036	0.1131
Leishmania major	myo-inositol-1(or 4)-monophosphatase 1, putative	0.0038	0.0137	0.0385
Trypanosoma cruzi	histone deacetylase 1, putative	0.0063	0.0333	0.1148
Plasmodium falciparum	histone deacetylase 1	0.0063	0.0333	0.1148
Trichomonas vaginalis	histone deacetylase, putative	0.0063	0.0333	1
Brugia malayi	Inositol-1	0.0038	0.0137	0.0141
Schistosoma mansoni	acetyl-CoA C-acetyltransferase	0.0023	0.0016	0.0051
Loa Loa (eye worm)	inositol-1	0.0038	0.0137	0.0432
Trypanosoma brucei	telomerase reverse transcriptase	0.0344	0.2605	1
Echinococcus granulosus	geminin	0.0177	0.1254	0.3909
Trichomonas vaginalis	histone deacetylase, putative	0.0063	0.0333	1
Loa Loa (eye worm)	RNA recognition domain-containing protein domain-containing protein	0.0066	0.036	0.1131
Toxoplasma gondii	RNA-directed DNA polymerase	0.0344	0.2605	1
Brugia malayi	RNA binding protein	0.0066	0.036	0.0451
Brugia malayi	RNA recognition motif domain containing protein	0.0066	0.036	0.0451
Mycobacterium leprae	DIHYDROFOLATE REDUCTASE DFRA (DHFR) (TETRAHYDROFOLATE DEHYDROGENASE)	0.0415	0.3184	1
Echinococcus multilocularis	bromodomain adjacent to zinc finger domain	0.0062	0.0329	0.0989
Toxoplasma gondii	bifunctional dihydrofolate reductase-thymidylate synthase	0.0159	0.111	0.4174
Trypanosoma cruzi	myo-inositol-1(or 4)-monophosphatase 1, putative	0.0038	0.0137	0.0385
Loa Loa (eye worm)	histone deacetylase 3	0.0063	0.0333	0.1047
Entamoeba histolytica	histone deacetylase, putative	0.0063	0.0333	1
Brugia malayi	Histone deacetylase 1	0.0063	0.0333	0.0414
Trypanosoma cruzi	myo-inositol-1(or 4)-monophosphatase 1, putative	0.0038	0.0137	0.0385
Trichomonas vaginalis	histone deacetylase, putative	0.0063	0.0333	1
Echinococcus granulosus	p2X purinoceptor 4	0.0071	0.0398	0.1206
Loa Loa (eye worm)	TAR-binding protein	0.0066	0.036	0.1131
Trichomonas vaginalis	histone deacetylase 1, 2 ,3, putative	0.0063	0.0333	1
Mycobacterium tuberculosis	Dihydrofolate reductase DfrA (DHFR) (tetrahydrofolate dehydrogenase)	0.0415	0.3184	1
Echinococcus multilocularis	bromodomain adjacent to zinc finger domain	0.0037	0.0129	0.0356
Leishmania major	histone deacetylase, putative	0.0063	0.0333	0.1148
Loa Loa (eye worm)	hypothetical protein	0.0074	0.0422	0.1326
Loa Loa (eye worm)	histone deacetylase 1	0.0063	0.0333	0.1047
Schistosoma mansoni	P2X receptor subunit	0.0071	0.0398	0.1251
Schistosoma mansoni	tar DNA-binding protein	0.0066	0.036	0.1131
Giardia lamblia	Telomerase catalytic subunit	0.0344	0.2605	1
Loa Loa (eye worm)	hypothetical protein	0.0044	0.0186	0.0583
Echinococcus multilocularis	p2X purinoceptor 4	0.0071	0.0398	0.1206
Schistosoma mansoni	P2X receptor subunit	0.0071	0.0398	0.1251
Brugia malayi	dihydrofolate reductase family protein	0.0415	0.3184	0.4381
Plasmodium vivax	bifunctional dihydrofolate reductase-thymidylate synthase, putative	0.0159	0.111	0.4174
Mycobacterium ulcerans	dihydrofolate reductase DfrA	0.0415	0.3184	1
Trichomonas vaginalis	histone deacetylase, putative	0.0063	0.0333	1
Schistosoma mansoni	histone deacetylase	0.0063	0.0333	0.1047
Brugia malayi	Telomerase reverse transcriptase	0.0914	0.7221	1
Trichomonas vaginalis	histone deacetylase 1, 2 ,3, putative	0.0063	0.0333	1
Trichomonas vaginalis	histone deacetylase 1, 2 ,3, putative	0.0063	0.0333	1
Echinococcus multilocularis	p2X purinoceptor 4	0.0071	0.0398	0.1206
Schistosoma mansoni	hypothetical protein	0.0177	0.1254	0.394
Plasmodium vivax	telomerase reverse transcriptase, putative	0.0344	0.2605	1
Echinococcus granulosus	bromodomain adjacent to zinc finger domain	0.0037	0.0129	0.0356
Loa Loa (eye worm)	dihydrofolate reductase	0.0415	0.3184	1
Echinococcus multilocularis	geminin	0.0177	0.1254	0.3909
Echinococcus granulosus	inositol monophosphatase 1	0.0038	0.0137	0.0383
Schistosoma mansoni	P2X receptor subunit	0.0071	0.0398	0.1251
Schistosoma mansoni	tar DNA-binding protein	0.0066	0.036	0.1131
Trypanosoma brucei	inositol-1(or 4)-monophosphatase 1, putative	0.0038	0.0137	0.0385
Leishmania major	dihydrofolate reductase-thymidylate synthase	0.0159	0.111	0.4174
Trichomonas vaginalis	histone deacetylase, putative	0.0063	0.0333	1
Echinococcus multilocularis	dihydrofolate reductase	0.0415	0.3184	1
Schistosoma mansoni	dihydrofolate reductase	0.0415	0.3184	1
Echinococcus granulosus	dihydrofolate reductase	0.0415	0.3184	1
Echinococcus multilocularis	inositol monophosphatase 1	0.0038	0.0137	0.0383
Brugia malayi	Dihydrofolate reductase	0.0415	0.3184	0.4381
Leishmania major	telomerase reverse transcriptase, putative	0.0344	0.2605	1
Schistosoma mansoni	tar DNA-binding protein	0.0066	0.036	0.1131
Echinococcus granulosus	histone deacetylase 1	0.0063	0.0333	0.1001
Echinococcus granulosus	bromodomain adjacent to zinc finger domain	0.0062	0.0329	0.0989
Echinococcus multilocularis	tar DNA binding protein	0.0066	0.036	0.1086
Loa Loa (eye worm)	hypothetical protein	0.0063	0.0333	0.1047
Plasmodium falciparum	telomerase reverse transcriptase	0.0344	0.2605	1
Trichomonas vaginalis	histone deacetylase, putative	0.0063	0.0333	1
Echinococcus granulosus	tar DNA binding protein	0.0066	0.036	0.1086
Echinococcus multilocularis	histone deacetylase 3	0.0063	0.0333	0.1001
Loa Loa (eye worm)	hypothetical protein	0.004	0.0149	0.047
Brugia malayi	histone deacetylase 3 (HD3)	0.0063	0.0333	0.0414
Schistosoma mansoni	bromodomain containing protein	0.0066	0.0359	0.1129
Brugia malayi	hypothetical protein	0.0026	0.0039	0.0003
Chlamydia trachomatis	dihydrofolate reductase	0.0415	0.3184	0.5
Echinococcus multilocularis	p2X purinoceptor 4	0.0071	0.0398	0.1206
Wolbachia endosymbiont of Brugia malayi	fructose-1,6-bisphosphatase	0.0038	0.0137	0.5
Toxoplasma gondii	histone deacetylase HDAC2	0.0063	0.0333	0.1148
Trypanosoma cruzi	dihydrofolate reductase-thymidylate synthase	0.0159	0.111	0.4174
Schistosoma mansoni	tar DNA-binding protein	0.0066	0.036	0.1131
Schistosoma mansoni	inositol monophosphatase	0.0038	0.0137	0.0432
Brugia malayi	histone deacetylase 1 (HD1)	0.0063	0.0333	0.0414
Schistosoma mansoni	histone deacetylase	0.0063	0.0333	0.1047
Trypanosoma brucei	dihydrofolate reductase-thymidylate synthase	0.0159	0.111	0.4174
Leishmania major	histone deacetylase, putative	0.0063	0.0333	0.1148

Activities

Activity type	Activity value	Assay description	Source	Reference
IC50 (functional)	= 2.1 nM	Activity was evaluated against HCT-8 tumor cells	ChEMBL.	8632413
IC50 (functional)	= 2.1 nM	Activity was evaluated against HCT-8 tumor cells	ChEMBL.	8632413
Inhibition (functional)	= 1 %	GSK_TCMDC: Inhibition of Plasmodium falciparum 3D7 LDH activity, using an LDH reporter assay. Test compounds present at 2uM	ChEMBL.	20485427
Inhibition (functional)	= 63.64 %	ST_JUDE_LEISH: Cytotoxicity at 2uM final concentration against transgenic Leishmania Mexicana promastigotes LmGT2 that are glucose transport deficient and complemented with the L. Mexicana glucose transporter 2. Activity is measured by by DNA content using SYBR green in vitro	ChEMBL.	No reference
Inhibition (functional)	= 69 %	GSK_TCMDC: Percent inhibition of human HepG2 cell line. Test compounds present at 10uM.	ChEMBL.	20485427
Inhibition (functional)	= 71.66 %	ST_JUDE_LEISH: Cytotoxicity at 2uM final concentration against transgenic Leishmania Mexicana promastigotes LmGLUT1 that are glucose transport deficient and complemented with the human glucose transporter GLUT1. Activity is measured by DNA content using SYBR green in vitro	ChEMBL.	No reference
Inhibition (functional)	= 77.16 %	ST_JUDE_LEISH: Cytotoxicity at 2uM final concentration against transgenic Leishmania Mexicana promastigotes LmPfHT that are glucose transport deficient and complemented with the Plasmodium falciparum hexose transporter. Activity is measured by by DNA content using SYBR green in vitro	ChEMBL.	No reference
Inhibition (functional)	= 85 %	GSK_TCMDC: Inhibition of Plasmodium falciparum Dd2 in whole red blood cells, using parasite LDH activity as an index of growth. Test compounds present at 2uM	ChEMBL.	20485427
Inhibition (functional)	= 97 %	GSK_TCMDC: Inhibition of Plasmodium falciparum 3D7 in whole red blood cells, using parasite LDH activity as an index of growth. Test compounds present at 2uM	ChEMBL.	20485427
Inhibition frequency index (IFI) (functional)	= 9.15	Inhibition Frequency Index (IFI)	GSK.	20485427
Ki (binding)	= 0.0071 nM	Inhibition of Dihydrofolate reductase enzyme from Candida albicans	ChEMBL.	8632413
Ki (binding)	= 0.0071 nM	Inhibition of Dihydrofolate reductase enzyme from Candida albicans	ChEMBL.	8632413
Ki (binding)	= 0.4 nM	Inhibition of human recombinant Dihydrofolate reductase enzyme	ChEMBL.	8632413
Ki (binding)	= 0.4 nM	Inhibition of human recombinant Dihydrofolate reductase enzyme	ChEMBL.	8632413
MIC (functional)	= 0.025 ug ml-1	Minimum inhibitory concentration evaluated against Candida albicans	ChEMBL.	8632413
MIC (functional)	= 0.025 ug ml-1	Minimum inhibitory concentration evaluated against Candida albicans	ChEMBL.	8632413
Percent growth inhibition (functional)	= 1 %	Percent inhibition of P. falciparum lactate dehydrogenase activity (at 2 uM)	GSK.	20485427
Percent growth inhibition (functional)	= 69 %	Percent inhibition of HepG2 growth (at 10 uM)	GSK.	20485427
Percent growth inhibition (functional)	= 85 %	Percent inhibition of P. falciparum Dd2 growth (at 2 uM)	GSK.	20485427
Percent growth inhibition (functional)	= 97 %	Percent inhibition of P. falciparum 3D7 growth (at 2 uM)	GSK.	20485427
XC50 (functional)	= 8.49	XC50 determination of P. falciparum 3D7 growth	GSK.	20485427
XC50 (functional)	= 0.0032 uM	GSK_TCMDC: Inhibition of Plasmodium falciparum 3D7 in whole erythrocytes, using parasite LDH activity as an index of growth.	ChEMBL.	20485427

Phenotypes

Whole-cell/tissue/organism interactions

Species name	Source	Reference	Is orphan
Homo sapiens	ChEMBL23	8632413

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: CHEMBL424170
Search by GSK
PubChem: 467899

Bibliographic References

2 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 302058