| Drug General Information |
| Drug ID |
D01UMT
|
| Former ID |
DCL000366
|
| Drug Name |
Ro 31-7453
|
| Synonyms |
Bisindolylmaleimide deriv. 44; MKC-1; Ro-31-7453; 3-(1-methylindol-3-yl)-4-(1-methyl-6-nitroindol-3-yl)pyrrole-2,5-dione
|
| Drug Type |
Small molecular drug
|
| Indication |
Solid tumours [ICD9: 140-199, 210-229; ICD10:C00-D48]
|
Phase 2 |
[1]
|
|---|
| Therapeutic Class |
Anticancer Agents
|
| Company |
Hoffmann La Roche
|
| Structure |
|
Download
2D MOL
3D MOL
|
| Formula |
C22H16N4O4
|
| Canonical SMILES |
CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=CN(C5=C4C=CC(=C5<br />)[N+](=O)[O-])C
|
| InChI |
1S/C22H16N4O4/c1-24-10-15(13-5-3-4-6-17(13)24)19-20(22(28)23-21(19)27)16-11-25(2)18-9-12(26(29)30)7-8-14(16)18/h3-11H,1-2H3,(H,23,27,28)
|
| InChIKey |
OVSKGTONMLKNPZ-UHFFFAOYSA-N
|
| CAS Number |
CAS 443912-18-3
|
| PubChem Compound ID |
|
| PubChem Substance ID |
8032392, 11060233, 14854715, 39300319, 52196594, 87550963, 103239096, 113907473, 128868698, 134339016, 135362948, 140926865, 142220978, 180389253, 198944951, 225112161, 226910178, 242839743, 252215829
|
| Target and Pathway |
| Target(s) |
Cell division protein kinase 4 |
Target Info |
Inhibitor |
[2]
|
|---|
| Cell division protein kinase 2 |
Target Info |
Inhibitor |
[2]
|
| Cell division control protein 2 homolog |
Target Info |
Inhibitor |
[2]
|
|
KEGG Pathway
|
Cell cycle
|
|
p53 signaling pathway
|
|
PI3K-Akt signaling pathway
|
|
Tight junction
|
|
T cell receptor signaling pathway
|
|
Hepatitis B
|
|
Measles
|
|
HTLV-I infection
|
|
Pathways in cancer
|
|
Viral carcinogenesis
|
|
Pancreatic cancer
|
|
Glioma
|
|
Melanoma
|
|
Bladder cancer
|
|
Chronic myeloid leukemia
|
|
Small cell lung cancer
|
|
Non-small cell lung cancerhsa04068:FoxO signaling pathway
|
|
Oocyte meiosis
|
|
Progesterone-mediated oocyte maturation
|
|
Herpes simplex infection
|
|
Epstein-Barr virus infection
|
|
Prostate cancer
|
|
Small cell lung cancerhsa04110:Cell cycle
|
|
Gap junction
|
|
NetPath Pathway
|
TCR Signaling Pathway
|
|
EGFR1 Signaling Pathway
|
|
RANKL Signaling PathwayNetPath_11:TCR Signaling PathwayNetPath_21:RANKL Signaling Pathway
|
|
PANTHER Pathway
|
p53 pathway
|
|
p53 pathway feedback loops 2
|
|
Pathway Interaction Database
|
Regulation of nuclear SMAD2/3 signaling
|
|
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
|
|
Validated targets of C-MYC transcriptional activation
|
|
ATF-2 transcription factor network
|
|
FOXM1 transcription factor network
|
|
Regulation of retinoblastoma proteinsmad2_3nuclearpathway:Regulation of nuclear SMAD2/3 signaling
|
|
Signaling events mediated by PRL
|
|
p73 transcription factor network
|
|
E2F transcription factor network
|
|
ATR signaling pathway
|
|
mTOR signaling pathway
|
|
IL2-mediated signaling events
|
|
FoxO family signaling
|
|
BARD1 signaling events
|
|
p53 pathway
|
|
Regulation of retinoblastoma proteinp73pathway:p73 transcription factor network
|
|
PLK1 signaling events
|
|
AP-1 transcription factor network
|
|
Retinoic acid receptors-mediated signaling
|
|
Reactome
|
Oxidative Stress Induced Senescence
|
|
Senescence-Associated Secretory Phenotype (SASP)
|
|
Oncogene Induced Senescence
|
|
RMTs methylate histone arginines
|
|
Transcriptional regulation of white adipocyte differentiation
|
|
Ubiquitin-dependent degradation of Cyclin D1
|
|
Cyclin D associated events in G1
|
|
Meiotic recombinationR-HSA-1538133:G0 and Early G1
|
|
Activation of ATR in response to replication stress
|
|
Regulation of APC/C activators between G1/S and early anaphase
|
|
SCF(Skp2)-mediated degradation of p27/p21
|
|
DNA Damage/Telomere Stress Induced Senescence
|
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Processing of DNA double-strand break ends
|
|
G2 Phase
|
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Orc1 removal from chromatin
|
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Cyclin E associated events during G1/S transition
|
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Cyclin A/B1 associated events during G2/M transition
|
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p53-Dependent G1 DNA Damage Response
|
|
Cyclin A:Cdk2-associated events at S phase entry
|
|
Meiotic recombination
|
|
Factors involved in megakaryocyte development and platelet productionR-HSA-110056:MAPK3 (ERK1) activation
|
|
E2F mediated regulation of DNA replication
|
|
G0 and Early G1
|
|
Cyclin B2 mediated events
|
|
Golgi Cisternae Pericentriolar Stack Reorganization
|
|
Cdc20:Phospho-APC/C mediated degradation of Cyclin A
|
|
Phosphorylation of the APC/C
|
|
Phosphorylation of Emi1
|
|
Condensation of Prophase Chromosomes
|
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MASTL Facilitates Mitotic Progression
|
|
Resolution of Sister Chromatid Cohesion
|
|
Condensation of Prometaphase Chromosomes
|
|
Regulation of PLK1 Activity at G2/M Transition
|
|
Activation of NIMA Kinases NEK9, NEK6, NEK7
|
|
Loss of Nlp from mitotic centrosomes
|
|
Recruitment of mitotic centrosome proteins and complexes
|
|
Loss of proteins required for interphase microtubule organization?from the centrosome
|
|
Recruitment of NuMA to mitotic centrosomes
|
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Depolymerisation of the Nuclear Lamina
|
|
Anchoring of the basal body to the plasma membrane
|
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MAPK6/MAPK4 signaling
|
|
G1/S-Specific Transcription
|
|
G2/M DNA replication checkpoint
|
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Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
|
|
WikiPathways
|
DNA Damage Response
|
|
G1 to S cell cycle control
|
|
Ovarian Infertility Genes
|
|
PPAR Alpha Pathway
|
|
Bladder Cancer
|
|
S Phase
|
|
Transcriptional Regulation of White Adipocyte Differentiation
|
|
Meiotic Recombination
|
|
Retinoblastoma (RB) in Cancer
|
|
Spinal Cord Injury
|
|
Integrated Pancreatic Cancer Pathway
|
|
Prostate Cancer
|
|
Signaling Pathways in Glioblastoma
|
|
TSH signaling pathway
|
|
Integrated Breast Cancer Pathway
|
|
Integrated Cancer pathway
|
|
Mitotic G1-G1/S phases
|
|
Cell Cycle
|
|
miRNA Regulation of DNA Damage ResponseWP707:DNA Damage Response
|
|
ID signaling pathway
|
|
DNA Replication
|
|
M/G1 Transition
|
|
Aryl Hydrocarbon Receptor
|
|
ATM Signaling Pathway
|
|
Oncostatin M Signaling Pathway
|
|
Synthesis of DNA
|
|
Regulation of DNA replication
|
|
Mitotic G2-G2/M phases
|
|
Factors involved in megakaryocyte development and platelet production
|
|
APC/C-mediated degradation of cell cycle proteins
|
|
Cell Cycle Checkpoints
|
|
TGF beta Signaling Pathway
|
|
MAP kinase activation in TLR cascade
|
|
RAF/MAP kinase cascade
|
|
Mitotic Prophase
|
|
Mitotic Prometaphase
|
|
BMI1
|
|
Regulation of Microtubule Cytoskeleton
|
|
miRNA Regulation of DNA Damage Response
|
| References |
| REF 1 | A phase 2 study of oral MKC-1, an inhibitor of importin-beta, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer. Invest New Drugs. 2012 Aug;30(4):1614-20. |
|---|
| REF 2 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. |
|---|
