Detailed information for compound 1824829
Basic information
Technical information
- Name: Unnamed compound
- MW: 580.563 | Formula: C29H35Cl2NO5S
-
H donors: 1
H acceptors: 5
LogP: 5.38
Rotable bonds: 9
Rule of 5 violations (Lipinski): 2 - SMILES: OC(=O)C[C@@]1(C)C[C@H](c2cccc(c2)Cl)[C@H](N(C1=O)[C@@H](C1CC1)CS(=O)(=O)C(C)(C)C)c1ccc(cc1)Cl
- InChi: 1S/C29H35Cl2NO5S/c1-28(2,3)38(36,37)17-24(18-8-9-18)32-26(19-10-12-21(30)13-11-19)23(20-6-5-7-22(31)14-20)15-29(4,27(32)35)16-25(33)34/h5-7,10-14,18,23-24,26H,8-9,15-17H2,1-4H3,(H,33,34)/t23-,24-,26-,29-/m1/s1
- InChiKey: HMKAZNCSHAJLSA-HIJQLYNKSA-N
Network
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Synonyms
No synonyms found for this compound
Targets
Known targets for this compound
| Species | Target name | Source | Bibliographic reference |
|---|---|---|---|
| Homo sapiens | cytochrome P450, family 3, subfamily A, polypeptide 4 | Starlite/ChEMBL | No references |
| Homo sapiens | MDM2 proto-oncogene, E3 ubiquitin protein ligase | Starlite/ChEMBL | References |
| Homo sapiens | tumor protein p53 | No 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 |
|---|---|---|---|---|---|
| Brugia malayi | cytochrome P450 | cytochrome P450, family 3, subfamily A, polypeptide 4 | 502 aa | 492 aa | 24.2 % |
Obtained from network model
Ranking Plot
Putative Targets List
| Species | Potential target | Raw | Global | Species |
|---|---|---|---|---|
| Echinococcus granulosus | carbonic anhydrase II | 0.0193 | 0.4541 | 0.3233 |
| Plasmodium falciparum | carbonic anhydrase | 0.0091 | 0.1933 | 0.5 |
| Brugia malayi | Carbonic anhydrase like protein 2 precursor | 0.0091 | 0.1933 | 0.4256 |
| Echinococcus multilocularis | carbonic anhydrase II | 0.0193 | 0.4541 | 0.3233 |
| Trypanosoma cruzi | glutathione-S-transferase/glutaredoxin, putative | 0.0158 | 0.3647 | 0.8032 |
| Loa Loa (eye worm) | hypothetical protein | 0.006 | 0.1141 | 0.2513 |
| Brugia malayi | Eukaryotic-type carbonic anhydrase family protein | 0.0091 | 0.1933 | 0.4256 |
| Mycobacterium ulcerans | cytochrome P450 185A4 Cyp185A4 | 0.0015 | 0 | 0.5 |
| Echinococcus multilocularis | tumor protein p63 | 0.0408 | 1 | 1 |
| Brugia malayi | Eukaryotic-type carbonic anhydrase family protein | 0.0193 | 0.4541 | 1 |
| Schistosoma mansoni | carbonic anhydrase-related | 0.0091 | 0.1933 | 0.2328 |
| Loa Loa (eye worm) | hypothetical protein | 0.0091 | 0.1933 | 0.4256 |
| Loa Loa (eye worm) | hypothetical protein | 0.0091 | 0.1933 | 0.4256 |
| Trypanosoma brucei | Prostaglandin E synthase | 0.0158 | 0.3647 | 0.8032 |
| Loa Loa (eye worm) | hypothetical protein | 0.0091 | 0.1933 | 0.4256 |
| Trypanosoma cruzi | carbonic anhydrase-like protein, putative | 0.0193 | 0.4541 | 1 |
| Schistosoma mansoni | carbonic anhydrase II (carbonate dehydratase II) | 0.0193 | 0.4541 | 1 |
| Trypanosoma cruzi | carbonic anhydrase-like protein, putative | 0.0193 | 0.4541 | 1 |
| Schistosoma mansoni | carbonic anhydrase II (carbonate dehydratase II) | 0.0193 | 0.4541 | 1 |
| Brugia malayi | Putative carbonic anhydrase 5 precursor | 0.0193 | 0.4541 | 1 |
| Loa Loa (eye worm) | eukaryotic-type carbonic anhydrase | 0.0193 | 0.4541 | 1 |
| Onchocerca volvulus | 0.0158 | 0.3647 | 1 | |
| Toxoplasma gondii | prostaglandin-E synthase | 0.0158 | 0.3647 | 1 |
| Brugia malayi | Eukaryotic-type carbonic anhydrase family protein | 0.0091 | 0.1933 | 0.4256 |
| Brugia malayi | hypothetical protein | 0.0158 | 0.3647 | 0.8032 |
| Schistosoma mansoni | carbonic anhydrase-related | 0.0091 | 0.1933 | 0.2328 |
| Loa Loa (eye worm) | eukaryotic-type carbonic anhydrase | 0.0091 | 0.1933 | 0.4256 |
| Loa Loa (eye worm) | carbonic anhydrase 3 | 0.0193 | 0.4541 | 1 |
| Loa Loa (eye worm) | hypothetical protein | 0.0158 | 0.3647 | 0.8032 |
| Brugia malayi | Eukaryotic-type carbonic anhydrase family protein | 0.0091 | 0.1933 | 0.4256 |
| Schistosoma mansoni | carbonic anhydrase-related | 0.0091 | 0.1933 | 0.2328 |
| Trypanosoma brucei | carbonic anhydrase-like protein | 0.0193 | 0.4541 | 1 |
| Brugia malayi | Carbonic anhydrase like protein 2 precursor | 0.0091 | 0.1933 | 0.4256 |
| Leishmania major | glutathione-S-transferase/glutaredoxin, putative | 0.0158 | 0.3647 | 0.8032 |
| Schistosoma mansoni | hypothetical protein | 0.0091 | 0.1933 | 0.2328 |
| Schistosoma mansoni | carbonic anhydrase | 0.0091 | 0.1933 | 0.2328 |
| Leishmania major | carbonic anhydrase-like protein | 0.0193 | 0.4541 | 1 |
| Trypanosoma cruzi | glutathione-S-transferase/glutaredoxin, putative | 0.0158 | 0.3647 | 0.8032 |
Activities
| Activity type | Activity value | Assay description | Source | Reference |
|---|---|---|---|---|
| Activity (ADMET) | = 28 % | Activation of human PXR at 2 uM relative to control | ChEMBL. | 25384157 |
| Activity (ADMET) | = 75 % | Time-dependent inhibition of CYP3A4 (unknown origin) assessed as remaining activity at 10 uM after 30 mins | ChEMBL. | 25384157 |
| CLH (ADMET) | = 16 uL/min | Intrinsic clearance in human hepatocytes measured per 10'6 cells | ChEMBL. | 24456472 |
| CLH (ADMET) | = 16 uL/min | Intrinsic clearance in human hepatocytes measured per 10'6 cells | ChEMBL. | 24548297 |
| CLH (ADMET) | = 25 uL/min | Intrinsic clearance in mouse hepatocytes measured per 10'6 cells | ChEMBL. | 24548297 |
| IC50 (binding) | = 0.0962 nM | BindingDB_Patents: Homogenous Time-Resolved Fluorescence Assay (HTRF). The standard assay conditions for the in vitro HTRF assay consisted of a 50 ul total reaction volume in black 384-well Costar polypropylene plates in 1PBS buffer pH 7.4, 1 mM DTT, 0.1% BSA, 2.5 nM GST-hMDM2 (aa 1-188), 5 nM biotinylated-p53 (aa 1-83), 1.8 nM SA-XLent (Cisbio; Bedford, Mass.), 0.6 nM anti-GST cryptate monoclonal antibody (Cisbio; Bedford, Mass.) and 200 mM KF. Amino acid residues 1-188 of human MDM2 were expressed as an amino-terminal glutathione S-transferase (GST) fusion protein (GST-hMDM2) in Escherichia coli. Residues 1-83 of human p53 were expressed as an amino-terminal AviTag-TrxA-6His fusion protein (biotinylated p53) in E. coli. Each protein was purified from cell paste by affinity chromatography.Specifically, 10 uL of GST-hMDM2 was incubated with 10 ul of diluted compound (various concentrations, serially diluted) in 10% DMSO for 20 minutes at room temperature. 20 uL of biotinylated-p53 was added to the GST-hMDM2+compound mixture. | ChEMBL. | No reference |
| IC50 (binding) | = 0.0962 nM | BindingDB_Patents: Homogenous Time-Resolved Fluorescence Assay (HTRF). The standard assay conditions for the in vitro HTRF assay consisted of a 50 ul total reaction volume in black 384-well Costar polypropylene plates in 1PBS buffer pH 7.4, 1 mM DTT, 0.1% BSA, 2.5 nM GST-hMDM2 (aa 1-188), 5 nM biotinylated-p53 (aa 1-83), 1.8 nM SA-XLent (Cisbio; Bedford, Mass.), 0.6 nM anti-GST cryptate monoclonal antibody (Cisbio; Bedford, Mass.) and 200 mM KF. Amino acid residues 1-188 of human MDM2 were expressed as an amino-terminal glutathione S-transferase (GST) fusion protein (GST-hMDM2) in Escherichia coli. Residues 1-83 of human p53 were expressed as an amino-terminal AviTag-TrxA-6His fusion protein (biotinylated p53) in E. coli. Each protein was purified from cell paste by affinity chromatography.Specifically, 10 uL of GST-hMDM2 was incubated with 10 ul of diluted compound (various concentrations, serially diluted) in 10% DMSO for 20 minutes at room temperature. 20 uL of biotinylated-p53 was added to the GST-hMDM2+compound mixture. | ChEMBL. | No reference |
| IC50 (binding) | = 0.1 nM | Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of interaction with human p53 after 1 hr by HTRF assay | ChEMBL. | 24456472 |
| IC50 (binding) | = 0.1 nM | Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay | ChEMBL. | 24548297 |
| IC50 (binding) | = 0.1 nM | Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in serum free buffer incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay | ChEMBL. | 24601644 |
| IC50 (binding) | = 0.1 nM | Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay | ChEMBL. | 25384157 |
| IC50 (binding) | = 0.1 nM | Homogenous Time-Resolved Fluorescence Assay (HTRF2 Assay) | BINDINGDB. | No reference |
| IC50 (binding) | = 1.1 nM | Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in buffer containing 15% human serum incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay | ChEMBL. | 24548297 |
| IC50 (binding) | = 1.1 nM | Binding affinity to GST-thrombin-tagged human MDM2 (1 to 188) expressed in Escherichia coli assessed as inhibition of interaction with p53 in buffer containing 15% human serum incubated for 20 mins prior to p53 addition measured after 60 mins by HTRF assay | ChEMBL. | 24601644 |
| IC50 (binding) | = 1.1 nM | Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as inhibition of interaction with human p53 preincubated with compound for 20 mins by HTRF assay in presence of 15% human serum | ChEMBL. | 25384157 |
| IC50 (functional) | = 1.6 nM | Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum | ChEMBL. | 24456472 |
| IC50 (functional) | = 1.6 nM | Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 16 hrs by Click-iT EdU HCS assay in presence of 10% human serum | ChEMBL. | 25384157 |
| IC50 (functional) | = 2 nM | Cytotoxicity against human SJSA1 cells assessed as growth inhibition after 16 hrs by EdU incorporation assay in presence of 10% human serum | ChEMBL. | 24601644 |
| IC50 (binding) | = 18.1 nM | Binding affinity to MDM2 in human SJSA1 cells assessed as induction of p21 gene level after 7 hrs by qRT-PCR assay in presence of 10% human serum | ChEMBL. | 25384157 |
| IC50 (ADMET) | > 27 uM | Inhibition of CYP3A4 (unknown origin) using midazolam as substrate | ChEMBL. | 24601644 |
| Inhibition (ADMET) | < 10 % | Inhibition of CYP3A4 (unknown origin) at 3 uM | ChEMBL. | 25384157 |
Phenotypes
Whole-cell/tissue/organism interactions
| Species name | Source | Reference | Is orphan |
|---|---|---|---|
| Homo sapiens | ChEMBL23 | 24456472 |
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: CHEMBL3125537
Bibliographic References
4 literature references were collected for this gene.
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