MI-63 : An azaspiro compound resulting from the formal fusion of position 3 of 6-chloro-oxindole with position 3 of (2R,3SS5S)-3-(3-chloro-2-fluorophenyl)-5-(2,2-dimethylpropyl)-N-[2-(morpholin-4-yl)ethyl]pyrrolidine-2-carboxamide. It is a potent inhibitor of the MDM2-p53 interaction. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 11512578 |
| CHEMBL ID | 379173 |
| CHEBI ID | 134602 |
| SCHEMBL ID | 2759820 |
| Synonym |
|---|
| mi-63 |
| CHEBI:134602 |
| (2'r,3s,4's,5'r)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-n-[2-(morpholin-4-yl)ethyl]-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide |
| jmc493432 compound 8 |
| bdbm31202 |
| CHEMBL379173 |
| SCHEMBL2759820 |
| 908027-21-4 |
| (2'r,3s,4's,5'r) 6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-morpholin-4-yl-ethyl)-amide |
| (2'r,3s,3's,5'r)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-n-(2-morpholin-4-ylethyl)-2-oxospiro[1h-indole-3,4'-pyrrolidine]-2'-carboxamide |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model." | ( Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Chen, J; Ding, K; Kang, S; McEachern, D; Miller, R; Nikolovska-Coleska, Z; Qin, D; Qiu, S; Shangary, S; Wang, G; Wang, S; Yang, D; Yu, S, 2009) | 0.35 |
| Role | Description |
|---|---|
| apoptosis inducer | Any substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| azaspiro compound | An azaspiro compound is a spiro compound in which at least one of the cyclic components is a nitrogen heterocyle. |
| morpholines | Any compound containing morpholine as part of its structure. |
| oxindoles | Any member of the class of indolones whose structure is based on an oxindole (2-indolone) skeleton. |
| pyrrolidines | Any of a class of heterocyclic amines having a saturated five-membered ring. |
| monochlorobenzenes | Any member of the class of chlorobenzenes containing a mono- or poly-substituted benzene ring in which only one substituent is chlorine. |
| monofluorobenzenes | Any member of the class of fluorobenzenes containing a mono- or poly-substituted benzene ring carrying a single fluorine substitutent. |
| secondary carboxamide | A carboxamide resulting from the formal condensation of a carboxylic acid with a primary amine; formula RC(=O)NHR(1). |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Protein Mdm4 | Homo sapiens (human) | Ki | 55.0000 | 5.8600 | 5.8600 | 5.8600 | AID1118053 |
| Cellular tumor antigen p53 | Homo sapiens (human) | IC50 (µMol) | 0.0150 | 0.0006 | 0.8850 | 8.2000 | AID706601; AID706602 |
| Cellular tumor antigen p53 | Homo sapiens (human) | Ki | 27.5015 | 0.0030 | 1.0736 | 5.8600 | AID1118052; AID1118053 |
| Apoptosis regulator Bcl-2 | Homo sapiens (human) | IC50 (µMol) | 50.0000 | 0.0010 | 0.5763 | 4.3000 | AID265958 |
| E3 ubiquitin-protein ligase Mdm2 | Homo sapiens (human) | IC50 (µMol) | 3.6677 | 0.0006 | 0.3582 | 10.0000 | AID265956; AID265957; AID442432; AID706601; AID706602 |
| E3 ubiquitin-protein ligase Mdm2 | Homo sapiens (human) | Ki | 0.0027 | 0.0009 | 0.1981 | 1.2400 | AID1118052; AID1799114; AID265955; AID442432 |
| Bcl-2-like protein 1 | Homo sapiens (human) | IC50 (µMol) | 50.0000 | 0.0003 | 1.0482 | 9.5400 | AID265959 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID442438 | Selectivity index, ratio of IC50 for human HCT116 cells expressing wild type p53 gene to IC50 for human HCT116 cells deficient in p53 gene expression | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID706602 | Inhibition of human MDM2-p53 interaction after 18 hrs by HTRF assay in presence of 15% human serum | 2012 | Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11 | Structure-based design of novel inhibitors of the MDM2-p53 interaction. |
| AID621851 | Growth inhibition of human HCT116 cells expressing MDM2 by SRB assay | 2011 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 21, Issue:19 | MDM2-p53 protein-protein interaction inhibitors: a-ring substituted isoindolinones. |
| AID265958 | Displacement of Flu-Bid from human recombinant Bcl2 receptor | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265956 | Antiproliferative activity against human LnCAP cell line with wild type p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442435 | Selectivity index, ratio of IC50 for human SJSA1 cells expressing wild type p53 gene to IC50 for human Saos2 cells deficient in p53 gene expression | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442433 | Growth inhibition of human SJSA1 cells expressing wild type p53 gene after 4 days by WST8 dye reduction assay | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265960 | Increase in p53 level in human LNCaP cell line with wild type p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442443 | Oral bioavailability in Sprague-Dawley rat at 25 mg/kg | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID706601 | Inhibition of human MDM2-p53 interaction after 18 hrs by HTRF assay | 2012 | Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11 | Structure-based design of novel inhibitors of the MDM2-p53 interaction. |
| AID442434 | Growth inhibition of human Saos2 cells deficient in p53 gene expression after 4 days by WST8 dye reduction assay | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID1118053 | Inhibition of p53 interaction to MDMX (unknown origin) by fluorescence polarization assay | 2011 | MedChemComm, , Volume: 2 | The p53-MDM2/MDMX axis - A chemotype perspective. |
| AID265955 | Displacement of PMDM6-F from human recombinant MDM2 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID621852 | Growth inhibition of p53 deficient human HCT116 cells expressing MDM2 by SRB assay | 2011 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 21, Issue:19 | MDM2-p53 protein-protein interaction inhibitors: a-ring substituted isoindolinones. |
| AID265959 | Displacement of Flu-Bid from human recombinant Bcl-xL receptor | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265962 | Increase in p21 level in human LNCaP cell line with wild type p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442441 | AUC (0 to t) in Sprague-Dawley rat at 25 mg/kg, po | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID621853 | Growth inhibition of human A2780 cells expressing MDM2 by SRB assay | 2011 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 21, Issue:19 | MDM2-p53 protein-protein interaction inhibitors: a-ring substituted isoindolinones. |
| AID621850 | Growth inhibition of human SJSA1 cells expressing MDM2 by SRB assay | 2011 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 21, Issue:19 | MDM2-p53 protein-protein interaction inhibitors: a-ring substituted isoindolinones. |
| AID442436 | Growth inhibition of human HCT116 cells expressing wild type p53 gene after 4 days by WST8 dye reduction assay | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265961 | Increase in MDM2 level in human LNCaP cell line with wild type p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442432 | Inhibition of his-tagged human recombinant MDM2 binding to p53-based peptide PMDM6-F by fluorescence polarization assay | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID1118052 | Inhibition of p53 interaction to MDM2 (unknown origin) by fluorescence polarization assay | 2011 | MedChemComm, , Volume: 2 | The p53-MDM2/MDMX axis - A chemotype perspective. |
| AID442437 | Growth inhibition of human HCT116 cells deficient in p53 gene expression after 4 days by WST8 dye reduction assay | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID621854 | Growth inhibition of human A2780/CP70 cells expressing isogenically paired p53 mutant by SRB assay | 2011 | Bioorganic & medicinal chemistry letters, Oct-01, Volume: 21, Issue:19 | MDM2-p53 protein-protein interaction inhibitors: a-ring substituted isoindolinones. |
| AID265964 | Increase in MDM2 level in human PC3 cell line with deleted p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265957 | Antiproliferative activity against human PC3 cell line with deleted p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265965 | Increase in p21 level in human PC3 cell line with deleted p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442440 | Cmax in Sprague-Dawley rat at 25 mg/kg, po | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID265963 | Increase in p53 level in human PC3 cell line with deleted p53 | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| AID442442 | Terminal half life in Sprague-Dawley rat at 25 mg/kg, po | 2009 | Journal of medicinal chemistry, Dec-24, Volume: 52, Issue:24 | Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. |
| AID1799114 | Fluorescence Polarization-Based (FP-Based) Binding Assay from Article 10.1021/jm051122a: \\Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction.\\ | 2006 | Journal of medicinal chemistry, Jun-15, Volume: 49, Issue:12 | Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 2 (40.00) | 29.6817 |
| 2010's | 3 (60.00) | 24.3611 |
| 2020's | 0 (0.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.
| This Compound (35.57) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 0 (0.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 5 (100.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||