Page last updated: 2024-11-13
ro3280
Description
Research Excerpts
Clinical Trials
Roles
Classes
Pathways
Study Profile
Bioassays
Related Drugs
Related Conditions
Protein Interactions
Research Growth
Market Indicators
Description
RO3280: inhibits polo-like kinase 1; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
Cross-References
| ID Source | ID |
|---|---|
| PubMed CID | 25015677 |
| CHEMBL ID | 2392553 |
| SCHEMBL ID | 1559146 |
| MeSH ID | M000609847 |
Synonyms (41)
| Synonym |
|---|
| dtxcid7028485 |
| cas-1062243-51-9 |
| NCGC00257406-01 |
| dtxsid4048511 , |
| pharmagsid_48511 |
| tox21_303518 |
| bdbm50435735 |
| chembl2392553 , |
| S7248 |
| 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-n-(1-methyl-piperidin-4-yl)-benzamide |
| 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide |
| ro3280 |
| CS-1673 |
| HY-15161 |
| SCHEMBL1559146 |
| 4-((9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino)-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide |
| 1062243-51-9 |
| gtpl9403 |
| compound 7 [pmid: 22172702] |
| 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide |
| AKOS026750574 |
| 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide |
| 79C , |
| ro5203280 |
| ro 3280 |
| HMS3653O21 |
| 4-[(9-cyclopentyl-7,7-difluoro-6,7,8,9-tetrahydro-5-methyl-6-oxo-5h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxy-n-(1-methyl-4-piperidinyl)benzamide |
| NCGC00386371-04 |
| ro3280, >=98% (hplc) |
| SW219316-1 |
| FT-0744236 |
| BCP07189 |
| EX-A2150 |
| ro-5203280 |
| SB19474 |
| CCG-269974 |
| F84977 |
| nsc-762154 |
| nsc762154 |
| AS-78052 |
| tpki-24 |
Research Excerpts
Treatment
| Excerpt | Reference | Relevance |
|---|---|---|
| "RO3280 treatment regulated several apoptosis-associated genes." | ( Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells. Cao, L; Du, XJ; Fang, F; Feng, X; Hu, SY; Jin, MF; Li, G; Li, YH; Li, YP; Li, ZH; Liu, L; Lu, J; Ni, J; Pan, J; Su, GH; Sun, LC; Tao, YF; Wang, J; Wang, NN; Wu, Y; Xiao, PF; Xu, LX; Xu, YY; Zhao, H; Zhao, WL; Zhou, HT; Zhu, XM, 2015) | 1.36 |
Bioavailability
| Excerpt | Reference | Relevance |
|---|---|---|
| "The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs." | ( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019) | 0.51 |
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
Protein Targets (37)
Potency Measurements
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| acetylcholinesterase | Homo sapiens (human) | Potency | 39.0574 | 0.0025 | 41.7960 | 15,848.9004 | AID1347395; AID1347397; AID1347398 |
| RAR-related orphan receptor gamma | Mus musculus (house mouse) | Potency | 12.5045 | 0.0060 | 38.0041 | 19,952.5996 | AID1159521; AID1159523 |
| SMAD family member 2 | Homo sapiens (human) | Potency | 50.3626 | 0.1737 | 34.3047 | 61.8120 | AID1346859; AID1346924 |
| SMAD family member 3 | Homo sapiens (human) | Potency | 50.3626 | 0.1737 | 34.3047 | 61.8120 | AID1346859; AID1346924 |
| GLI family zinc finger 3 | Homo sapiens (human) | Potency | 1.1156 | 0.0007 | 14.5928 | 83.7951 | AID1259368; AID1259369; AID1259392 |
| AR protein | Homo sapiens (human) | Potency | 4.8244 | 0.0002 | 21.2231 | 8,912.5098 | AID1259247; AID743035; AID743036; AID743042; AID743053; AID743054; AID743063 |
| caspase 7, apoptosis-related cysteine protease | Homo sapiens (human) | Potency | 22.2971 | 0.0133 | 26.9810 | 70.7614 | AID1346978 |
| estrogen receptor 2 (ER beta) | Homo sapiens (human) | Potency | 24.7035 | 0.0006 | 57.9133 | 22,387.1992 | AID1259377; AID1259378 |
| nuclear receptor subfamily 1, group I, member 3 | Homo sapiens (human) | Potency | 8.2681 | 0.0010 | 22.6508 | 76.6163 | AID1224838; AID1224839; AID1224893 |
| progesterone receptor | Homo sapiens (human) | Potency | 28.0704 | 0.0004 | 17.9460 | 75.1148 | AID1346795 |
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 16.9330 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| glucocorticoid receptor [Homo sapiens] | Homo sapiens (human) | Potency | 47.6241 | 0.0002 | 14.3764 | 60.0339 | AID720691; AID720692 |
| retinoic acid nuclear receptor alpha variant 1 | Homo sapiens (human) | Potency | 1.7639 | 0.0030 | 41.6115 | 22,387.1992 | AID1159552; AID1159553; AID1159555 |
| retinoid X nuclear receptor alpha | Homo sapiens (human) | Potency | 7.1139 | 0.0008 | 17.5051 | 59.3239 | AID1159531 |
| estrogen-related nuclear receptor alpha | Homo sapiens (human) | Potency | 9.4761 | 0.0015 | 30.6073 | 15,848.9004 | AID1224841; AID1224842; AID1224848; AID1224849; AID1259401; AID1259403 |
| farnesoid X nuclear receptor | Homo sapiens (human) | Potency | 12.0444 | 0.3758 | 27.4851 | 61.6524 | AID743217; AID743239 |
| pregnane X nuclear receptor | Homo sapiens (human) | Potency | 19.8723 | 0.0054 | 28.0263 | 1,258.9301 | AID1346982 |
| estrogen nuclear receptor alpha | Homo sapiens (human) | Potency | 1.1175 | 0.0002 | 29.3054 | 16,493.5996 | AID1259244; AID1259248; AID743069; AID743078; AID743079; AID743080; AID743091 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 23.9185 | 0.0010 | 8.3798 | 61.1304 | AID1645840 |
| peroxisome proliferator-activated receptor delta | Homo sapiens (human) | Potency | 14.1941 | 0.0010 | 24.5048 | 61.6448 | AID743215 |
| peroxisome proliferator activated receptor gamma | Homo sapiens (human) | Potency | 50.3626 | 0.0010 | 19.4141 | 70.9645 | AID743191 |
| vitamin D (1,25- dihydroxyvitamin D3) receptor | Homo sapiens (human) | Potency | 6.3403 | 0.0237 | 23.2282 | 63.5986 | AID743223 |
| caspase-3 | Homo sapiens (human) | Potency | 22.2971 | 0.0133 | 26.9810 | 70.7614 | AID1346978 |
| cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_a | Homo sapiens (human) | Potency | 12.5386 | 0.0017 | 23.8393 | 78.1014 | AID743083 |
| thyroid stimulating hormone receptor | Homo sapiens (human) | Potency | 11.3936 | 0.0016 | 28.0151 | 77.1139 | AID1259385; AID1259395 |
| Caspase-7 | Cricetulus griseus (Chinese hamster) | Potency | 3.1495 | 0.0067 | 23.4960 | 68.5896 | AID1346980 |
| caspase-3 | Cricetulus griseus (Chinese hamster) | Potency | 3.1495 | 0.0067 | 23.4960 | 68.5896 | AID1346980 |
| thyroid hormone receptor beta isoform 2 | Rattus norvegicus (Norway rat) | Potency | 0.3675 | 0.0003 | 23.4451 | 159.6830 | AID743065; AID743066; AID743067 |
| nuclear factor erythroid 2-related factor 2 isoform 1 | Homo sapiens (human) | Potency | 49.9169 | 0.0006 | 27.2152 | 1,122.0200 | AID743202 |
| Voltage-dependent calcium channel gamma-2 subunit | Mus musculus (house mouse) | Potency | 2.8070 | 0.0015 | 57.7890 | 15,848.9004 | AID1259244 |
| Cellular tumor antigen p53 | Homo sapiens (human) | Potency | 42.5694 | 0.0023 | 19.5956 | 74.0614 | AID651631; AID720552 |
| Glutamate receptor 2 | Rattus norvegicus (Norway rat) | Potency | 2.8070 | 0.0015 | 51.7393 | 15,848.9004 | AID1259244 |
| ATPase family AAA domain-containing protein 5 | Homo sapiens (human) | Potency | 2.0401 | 0.0119 | 17.9420 | 71.5630 | AID651632; AID720516 |
| Ataxin-2 | Homo sapiens (human) | Potency | 1.5785 | 0.0119 | 12.2221 | 68.7989 | AID651632 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Inhibition Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Serine/threonine-protein kinase PLK1 | Homo sapiens (human) | IC50 (µMol) | 0.0040 | 0.0001 | 0.7734 | 9.0000 | AID753523 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Activation Measurements
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Bromodomain-containing protein 4 | Homo sapiens (human) | Kd | 0.2157 | 0.0010 | 0.3691 | 8.9300 | AID1807750; AID1807751; AID1807752 |
| Bromodomain testis-specific protein | Homo sapiens (human) | Kd | 1.3633 | 0.0220 | 1.0083 | 4.8360 | AID1807754; AID1807755; AID1807756 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
Biological Processes (196)
Molecular Functions (55)
Ceullar Components (40)
Bioassays (30)
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1807756 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells by ITC analysis | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807758 | Inhibition of cell growth in HEK293T cells incubated for 72 hrs by CellTiter-blue reagent based assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807763 | Inhibition of PLK1 in HEK293T cells assessed as increase in p21 levels at 0.0001 to 10 uM incubated for 6 hrs by immunoblotting analysis | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807750 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRD4 expressed in Escherichia coli BL21 (DE3) cells by MST assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807761 | Inhibition of PLK1 in human MM1.S cells assessed as increase in p21 levels incubated for 6 hrs by immunoblotting analysis | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807753 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells assessed as change in melting temperature by DSF assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807755 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells by qPCR assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807757 | Inhibition of cell growth in human MM1.S cells incubated for 72 hrs by CellTiter-blue reagent based assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID753522 | Inhibition of PLK1 (21 to 351) (unknown origin) assessed as half life of dissociation rate using FAM-mTOR peptide as substrate | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID753517 | Volume of distribution at steady state in rat at 1 mg/kg, iv and 5 mg/kg, po | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID1807760 | Inhibition of PLK1 in human MM1.S cells assessed as reduction in c-Myc levels incubated for 6 hrs by immunoblotting analysis | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807752 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRD4 expressed in Escherichia coli BL21 (DE3) cells by ITC analysis | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID753516 | Oral bioavailability in rat at 5 mg/kg | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID753519 | Clearance in rat at 1 mg/kg, iv and 5 mg/kg, po | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID753521 | Antiproliferative activity against human HT-29 cells after 72 hrs by Cell Titer-Glo Assay | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID753518 | Half life in rat at 1 mg/kg, iv and 5 mg/kg, po | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID1807749 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRD4 expressed in Escherichia coli BL21 (DE3) cells assessed as change in melting temperature by DSF assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807754 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRDT expressed in Escherichia coli BL21 (DE3) cells by MST assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID753520 | Ratio of efflux ratio in pig LLC cells expressing MDR to efflux ratio in wild type pig LLC cells | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID753523 | Inhibition of PLK1 (unknown origin) using biotin-AGAGTVPESIHSFIGDGLV as substrate by TR-FRET assay | 2013 | Bioorganic & medicinal chemistry letters, Jun-15, Volume: 23, Issue:12 | Discovery of TAK-960: an orally available small molecule inhibitor of polo-like kinase 1 (PLK1). |
| AID1807751 | Binding affinity to recombinant human N-terminal hexaHis-tagged BRD4 expressed in Escherichia coli BL21 (DE3) cells by qPCR assay | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1807759 | Inhibition of PLK1 in HEK293T cells assessed as reduction in phosphorylation of TCTP at S46 residue at 30 to 100 nM incubated for 6 hrs by immunoblotting analysis | 2021 | Journal of medicinal chemistry, 11-11, Volume: 64, Issue:21 | Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors. |
| AID1345608 | Human FER tyrosine kinase (Fer family) | 2012 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2 | Identification of novel, potent and selective inhibitors of Polo-like kinase 1. |
| AID1345775 | Human polo like kinase 1 (Polo-like kinase (PLK) family) | 2012 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2 | Identification of novel, potent and selective inhibitors of Polo-like kinase 1. |
| AID1345801 | Human TTK protein kinase (TTK family) | 2012 | Bioorganic & medicinal chemistry letters, Jan-15, Volume: 22, Issue:2 | Identification of novel, potent and selective inhibitors of Polo-like kinase 1. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
Research
Studies (10)
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 6 (60.00) | 24.3611 |
| 2020's | 4 (40.00) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
Market Indicators
Research Demand Index: 17.29
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 moderate demand-to-supply ratio for research on this compound.
| This Compound (17.29) All Compounds (24.57) |
Study Types
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 1 (10.00%) | 5.53% |
| Reviews | 0 (0.00%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 9 (90.00%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||