Detailed information for compound 511492
Basic information
Technical information
- TDR Targets ID: 511492
- Name: 2-[(3R)-5-chloro-1'-[(5-chloro-2-fluorophenyl )methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrr olidine]-1-yl]acetic acid
- MW: 451.232 | Formula: C20H13Cl2FN2O5
-
H donors: 1
H acceptors: 5
LogP: 2.44
Rotable bonds: 4
Rule of 5 violations (Lipinski): 1 - SMILES: OC(=O)CN1c2ccc(cc2[C@@]2(C1=O)CC(=O)N(C2=O)Cc1cc(Cl)ccc1F)Cl
- InChi: 1S/C20H13Cl2FN2O5/c21-11-1-3-14(23)10(5-11)8-25-16(26)7-20(19(25)30)13-6-12(22)2-4-15(13)24(18(20)29)9-17(27)28/h1-6H,7-9H2,(H,27,28)/t20-/m1/s1
- InChiKey: IXKFWNVFUXXEFY-HXUWFJFHSA-N
Network
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Synonyms
- 2-[(3R)-5-chloro-1'-[(5-chloro-2-fluoro-phenyl)methyl]-2,2',5'-trioxo-spiro[indoline-3,3'-pyrrolidine]-1-yl]acetic acid
- 2-[(3R)-5-chloro-1'-[(5-chloro-2-fluorophenyl)methyl]-2,2',5'-trioxo-1-spiro[indoline-3,3'-pyrrolidine]yl]acetic acid
- 2-[(3R)-5-chloro-1'-[(5-chloro-2-fluoro-phenyl)methyl]-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidine]-1-yl]ethanoic acid
- 2-[(3R)-5-chloro-1'-(5-chloro-2-fluoro-benzyl)-2,2',5'-triketo-spiro[indoline-3,3'-pyrrolidine]-1-yl]acetic acid
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Homo sapiens | prostaglandin D2 receptor 2 | Starlite/ChEMBL | References |
| Mus musculus | prostaglandin D2 receptor 2 | Starlite/ChEMBL | References |
Predicted pathogen targets for this compound
By orthology
No druggable targets predicted by orthology data
By sequence similarity to non orthologous known druggable targets
No druggable targets predicted by sequence similarity
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Plasmodium falciparum | DNA (cytosine-5)-methyltransferase | 0.0022 | 0.0306 | 0.0306 |
| Echinococcus granulosus | guanine nucleotide binding protein Gs subunit | 0.0047 | 0.3788 | 1 |
| Schistosoma mansoni | cpg binding protein | 0.0037 | 0.2362 | 0.6235 |
| Schistosoma mansoni | cpg binding protein | 0.0037 | 0.2362 | 0.6235 |
| Giardia lamblia | Endonuclease/Exonuclease/phosphatase | 0.0019 | 0 | 0.5 |
| Trypanosoma brucei | cytosine-specific DNA methylase, putative | 0.0022 | 0.0306 | 1 |
| Leishmania major | modification methylase-like protein | 0.0022 | 0.0306 | 1 |
| Onchocerca volvulus | 0.0042 | 0.3111 | 1 | |
| Mycobacterium tuberculosis | Probable exodeoxyribonuclease III protein XthA (exonuclease III) (EXO III) (AP endonuclease VI) | 0.0019 | 0 | 0.5 |
| Echinococcus granulosus | cpg binding protein | 0.0037 | 0.2362 | 0.6235 |
| Toxoplasma gondii | DNA methyltransferase 2, putative | 0.0022 | 0.0306 | 0.0306 |
| Echinococcus granulosus | guanine nucleotide binding protein Gs subunit | 0.0047 | 0.3788 | 1 |
| Echinococcus multilocularis | DNA methyltransferase 2, putative | 0.0022 | 0.0306 | 0.0809 |
| Entamoeba histolytica | DNA (cytosine-5)-methyltransferase, putative | 0.0022 | 0.0306 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0042 | 0.3111 | 0.8213 |
| Brugia malayi | Disco-interacting protein 2 homolog | 0.0042 | 0.3111 | 0.8213 |
| Echinococcus multilocularis | guanine nucleotide binding protein G(s) subunit | 0.0047 | 0.3788 | 1 |
| Echinococcus granulosus | disco interacting protein 2 | 0.0042 | 0.3111 | 0.8213 |
| Echinococcus multilocularis | disco interacting protein 2 | 0.0042 | 0.3111 | 0.8213 |
| Schistosoma mansoni | DNA (cytosine-5)-methyltransferase | 0.0022 | 0.0306 | 0.0809 |
| Treponema pallidum | exodeoxyribonuclease (exoA) | 0.0019 | 0 | 0.5 |
| Loa Loa (eye worm) | GTP-binding regulatory protein Gs alpha-S chain | 0.0047 | 0.3788 | 1 |
| Echinococcus multilocularis | guanine nucleotide binding protein G(s) subunit | 0.0047 | 0.3788 | 1 |
| Schistosoma mansoni | Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein) | 0.0047 | 0.3788 | 1 |
| Brugia malayi | GTP-binding regulatory protein Gs alpha-S chain, putative | 0.0047 | 0.3788 | 1 |
| Trypanosoma cruzi | apurinic/apyrimidinic endonuclease | 0.0019 | 0 | 0.5 |
| Toxoplasma gondii | hypothetical protein | 0.0093 | 1 | 1 |
| Plasmodium vivax | DNA (cytosine-5)-methyltransferase, putative | 0.0022 | 0.0306 | 1 |
| Echinococcus granulosus | DNA methyltransferase 2, putative | 0.0022 | 0.0306 | 0.0809 |
| Trypanosoma cruzi | apurinic/apyrimidinic endonuclease, putative | 0.0019 | 0 | 0.5 |
| Trichomonas vaginalis | ap endonuclease, putative | 0.0019 | 0 | 0.5 |
| Schistosoma mansoni | Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein) | 0.0047 | 0.3788 | 1 |
| Schistosoma mansoni | cpg binding protein | 0.0037 | 0.2362 | 0.6235 |
| Toxoplasma gondii | C-5 cytosine-specific DNA methylase superfamily protein | 0.0022 | 0.0306 | 0.0306 |
| Trichomonas vaginalis | ap endonuclease, putative | 0.0019 | 0 | 0.5 |
| Loa Loa (eye worm) | CXXC zinc finger family protein | 0.0037 | 0.2362 | 0.6235 |
| Mycobacterium ulcerans | exodeoxyribonuclease III protein XthA | 0.0019 | 0 | 0.5 |
| Schistosoma mansoni | Guanine nucleotide-binding protein G(s) subunit alpha (Adenylate cyclase-stimulating G alpha protein) | 0.0047 | 0.3788 | 1 |
| Brugia malayi | CXXC zinc finger family protein | 0.0037 | 0.2362 | 0.6235 |
| Schistosoma mansoni | disco-interacting protein 2 (dip2) | 0.0042 | 0.3111 | 0.8213 |
| Wolbachia endosymbiont of Brugia malayi | exonuclease III | 0.0019 | 0 | 0.5 |
| Echinococcus multilocularis | cpg binding protein | 0.0037 | 0.2362 | 0.6235 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| AUC (ADMET) | = 339 ng.hr/ml | AUC (0 to last t) in beagle dog at 1 mg/kg, po | ChEMBL. | 18318469 |
| AUC (ADMET) | = 637 ng.hr/ml | AUC (0 to last t) in beagle dog at 1 mg/kg, iv | ChEMBL. | 18318469 |
| AUC (ADMET) | = 1180 ng.hr/ml | AUC (0 to last t) in rat at 1 mg/kg, iv | ChEMBL. | 18318469 |
| AUC (ADMET) | = 1910 ng.hr/ml | AUC (0 to last t) in rat at 5 mg/kg, po | ChEMBL. | 18318469 |
| CL (ADMET) | = 0.7 L/kg/hr | Clearance in rat at 1 mg/kg, iv | ChEMBL. | 18318469 |
| CL (ADMET) | = 2 L/kg/hr | Clearance in beagle dog at 1 mg/kg, iv | ChEMBL. | 18318469 |
| CL (ADMET) | = 5 uL/min | Intrinsic clearance per mg of protein in human liver microsomes at 3 uM | ChEMBL. | 18318469 |
| CL (ADMET) | = 19 uL/min | Intrinsic clearance per mg of protein in rat liver microsomes at 3 uM | ChEMBL. | 18318469 |
| Cmax (ADMET) | = 68.8 ng/ml | Cmax in beagle dog at 5 mg/kg, po | ChEMBL. | 18318469 |
| Cmax (ADMET) | = 163 ng/ml | Cmax in rat at 5 mg/kg, po | ChEMBL. | 18318469 |
| Cmax (ADMET) | = 1700 ng/ml | Cmax in rat at 1 mg/kg, iv | ChEMBL. | 18318469 |
| Cmax (ADMET) | = 1950 ng/ml | Cmax in beagle dog at 1 mg/kg, iv | ChEMBL. | 18318469 |
| F (ADMET) | = 32 % | Oral bioavailability in rat at 5 mg/kg | ChEMBL. | 18318469 |
| F (ADMET) | = 52 % | Oral bioavailability in beagle dog at 1 mg/kg | ChEMBL. | 18318469 |
| IC50 (functional) | = 7.3 nM | Antagonist activity at human CRTH2 receptor assessed as inhibiton of DK-PGD2-induced eosinophil chemotaxis | ChEMBL. | 18318469 |
| IC50 (functional) | = 7.3 nM | Antagonist activity at human CRTH2 receptor assessed as inhibiton of DK-PGD2-induced eosinophil chemotaxis | ChEMBL. | 18318469 |
| IC50 (functional) | = 66 nM | Antagonist activity at human CRTH2 receptor expressed in CHO cell membrane by [35S]GTPgammaS binding assay | ChEMBL. | 18318469 |
| IC50 (functional) | = 66 nM | Antagonist activity at human CRTH2 receptor expressed in CHO cell membrane by [35S]GTPgammaS binding assay | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostaglandin D2 receptor (unknown origin) | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostanoid EP2 receptor (unknown origin) | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostanoid EP3 receptor (unknown origin) | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostanoid EP4 receptor (unknown origin) | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostanoid FP receptor (unknown origin) | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostaglandin D2 receptor (unknown origin) | ChEMBL. | 18318469 |
| IC50 (binding) | > 30 uM | Inhibition of prostanoid EP2 receptor (unknown origin) | ChEMBL. | 18318469 |
| Ki (binding) | = 5 nM | Displacement of [3H]PGD2 from mouse CRTH2 receptor expressed in HEK293 cells | ChEMBL. | 18318469 |
| Ki (binding) | = 5 nM | Displacement of [3H]PGD2 from mouse CRTH2 receptor expressed in HEK293 cells | ChEMBL. | 18318469 |
| Ki (binding) | = 5.3 nM | Displacement of [3H]PGD2 from human CRTH2 receptor expressed in CHO cells | ChEMBL. | 18318469 |
| Ki (binding) | = 5.3 nM | Displacement of [3H]PGD2 from human CRTH2 receptor expressed in CHO cells | ChEMBL. | 18318469 |
| Log D | = -0.5 | Lipophilicity, log D of the compound | ChEMBL. | 18318469 |
| Papp (ADMET) | = 26.4 10^-6 cm/s | Apparent permeability across human Caco2 cell membrane at 10 uM | ChEMBL. | 18318469 |
| Papp (ADMET) | = 26.4 10^-6 cm/s | Apparent permeability across human Caco2 cell membrane at 10 uM | ChEMBL. | 18318469 |
| Papp (ADMET) | = 26 ucm/s | Apparent permeability of the compound in human Caco2 cells | ChEMBL. | 24900359 |
| t1/2 (ADMET) | = 3 hr | Half life in beagle dog at 1 mg/kg, iv | ChEMBL. | 18318469 |
| t1/2 (ADMET) | = 5.4 hr | Half life in rat at 5 mg/kg, po | ChEMBL. | 18318469 |
| t1/2 (ADMET) | = 13 hr | Half life in rat at 1 mg/kg, iv | ChEMBL. | 18318469 |
| Tmax (ADMET) | = 0 hr | Tmax in rat at 1 mg/kg, iv | ChEMBL. | 18318469 |
| Tmax (ADMET) | = 0 hr | Tmax in beagle dog at 1 mg/kg, iv | ChEMBL. | 18318469 |
| Tmax (ADMET) | = 1.5 hr | Tmax in rat at 5 mg/kg, po | ChEMBL. | 18318469 |
| Tmax (ADMET) | = 2.67 hr | Tmax in beagle dog at 5 mg/kg, po | ChEMBL. | 18318469 |
| Vdss (ADMET) | = 5 L/Kg | Volume of distribution at steady state in beagle dog at 1 mg/kg, iv | ChEMBL. | 18318469 |
| Vdss (ADMET) | = 7 L/Kg | Volume of distribution at steady state in rat at 1 mg/kg, iv | ChEMBL. | 18318469 |
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: CHEMBL260672
- PubChem: 24776306
Bibliographic References
1 literature reference was collected for this gene.
If you have references for this compound, please enter them in a user comment (below) or Contact us.