7-Hydroxystaurosporine

Identification

Name
7-Hydroxystaurosporine
Accession Number
DB01933  (EXPT03167)
Type
Small Molecule
Groups
Experimental, Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
KRX-0601 / NSC-638850 / UCN 01 / UCN-01
Categories
UNII
7BU5H4V94A
CAS number
112953-11-4
Weight
Average: 482.5304
Monoisotopic: 482.19540534
Chemical Formula
C28H26N4O4
InChI Key
PBCZSGKMGDDXIJ-HQCWYSJUSA-N
InChI
InChI=1S/C28H26N4O4/c1-28-25(35-3)15(29-2)12-18(36-28)31-16-10-6-4-8-13(16)19-21-22(27(34)30-26(21)33)20-14-9-5-7-11-17(14)32(28)24(20)23(19)31/h4-11,15,18,25,27,29,34H,12H2,1-3H3,(H,30,33)/t15-,18-,25-,27-,28+/m1/s1
IUPAC Name
(2S,3R,4R,6R,18R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1²,⁶.0⁷,²⁸.0⁸,¹³.0¹⁵,¹⁹.0²⁰,²⁷.0²¹,²⁶]nonacosa-8,10,12,14,16,19,21,23,25,27-decaene-16,18-diol
SMILES
[H][[email protected]]1(O)N=C(O)C2=C3C4=CC=CC=C4N4C3=C3N(C5=CC=CC=C5C3=C12)[[email protected]@]1(C)O[[email protected]]4([H])C[[email protected]@]([H])(NC)[[email protected]@]1([H])OC

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
U3-phosphoinositide-dependent protein kinase 1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of 7-Hydroxystaurosporine.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with 7-Hydroxystaurosporine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of 7-Hydroxystaurosporine.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with 7-Hydroxystaurosporine.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with 7-Hydroxystaurosporine.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of 7-Hydroxystaurosporine.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of 7-Hydroxystaurosporine.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
72271
PubChem Substance
46508077
ChemSpider
65225
BindingDB
17054
ChEMBL
CHEMBL1236539
Therapeutic Targets Database
DCL001064
HET
UCN
PDB Entries
1nvq / 1okz / 1pkd

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAccelerated Phase Chronic Myelogenous Leukemia / Adult Acute Megakaryoblastic Leukemia (M7) / Adult Acute Minimally Differentiated Myeloid Leukemia (M0) / Adult Acute Monoblastic Leukemia (M5a) / Adult Acute Monocytic Leukemia (M5b) / Adult Acute Myeloblastic Leukemia With Maturation (M2) / Adult Acute Myeloblastic Leukemia Without Maturation (M1) / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Acute Myelomonocytic Leukemia (M4) / Adult Acute Promyelocytic Leukemia (M3) / Adult Erythroleukemia (M6a) / Adult Pure Erythroid Leukemia (M6b) / Blastic Phase Chronic Myelogenous Leukemia / Myelodysplastic/Myeloproliferative Neoplasms / Previously Treated Myelodysplastic Syndromes / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Relapsing Chronic Myelogenous Leukemia / Secondary Acute Myeloid Leukemia / T-cell Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Adult Acute Myeloid Leukemia1
1CompletedTreatmentAdenocarcinoma of the Pancreas / Recurrent Pancreatic Cancer / Stage II Pancreatic Cancer / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer1
1CompletedTreatmentAdvanced Adult Primary Liver Cancer / Carcinoma of the Appendix / Estrogen Receptor-negative Breast Cancer / Extensive Stage Small Cell Lung Cancer / Gastrointestinal Stromal Tumors / HER2-Negative Breast Cancer / Metastatic Gastrointestinal Carcinoid Tumor / Ovarian Sarcoma / Ovarian Stromal Cancer / Progesterone Receptor-negative Breast Cancer / Recurrent Adenoid Cystic Carcinoma of the Oral Cavity / Recurrent Adult Primary Liver Cancer / Recurrent Anal Cancer / Recurrent Basal Cell Carcinoma of the Lip / Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor / Recurrent Breast Cancer / Recurrent Cervical Cancer / Recurrent Colon Cancer / Recurrent Endometrial Carcinoma / Recurrent Esophageal Cancer / Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity / Recurrent Extrahepatic Bile Duct Cancer / Recurrent Gallbladder Cancer / Recurrent Gastric Cancer / Recurrent Gastrointestinal Carcinoid Tumor / Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity / Recurrent Lymphoepithelioma of the Nasopharynx / Recurrent Lymphoepithelioma of the Oropharynx / Recurrent Metastatic Squamous Neck Cancer With Occult Primary / Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity / Recurrent Mucoepidermoid Carcinoma of the Oral Cavity / Recurrent Non-small Cell Lung Cancer / Recurrent Ovarian Epithelial Cancer / Recurrent Ovarian Germ Cell Tumor / Recurrent Pancreatic Cancer / Recurrent Prostate Cancer / Recurrent Rectal Cancer / Recurrent Salivary Gland Cancer / Recurrent Small Cell Lung Cancer / Recurrent Small Intestine Cancer / Recurrent Squamous Cell Carcinoma of the Hypopharynx / Recurrent Squamous Cell Carcinoma of the Larynx / Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity / Recurrent Squamous Cell Carcinoma of the Nasopharynx / Recurrent Squamous Cell Carcinoma of the Oropharynx / Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Recurrent Verrucous Carcinoma of the Larynx / Recurrent Verrucous Carcinoma of the Oral Cavity / Small Intestine Adenocarcinoma / Small Intestine Leiomyosarcoma / Small Intestine Lymphoma / Stage IV Adenoid Cystic Carcinoma of the Oral Cavity / Stage IV Anal Cancer / Stage IV Basal Cell Carcinoma of the Lip / Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor / Stage IV Breast Cancer / Stage IV Colon Cancer / Stage IV Endometrial Carcinoma / Stage IV Esophageal Cancer / Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity / Stage IV Gastric Cancer / Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity / Stage IV Lymphoepithelioma of the Nasopharynx / Stage IV Lymphoepithelioma of the Oropharynx / Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity / Stage IV Mucoepidermoid Carcinoma of the Oral Cavity / Stage IV Non-Small Cell Lung Cancer / Stage IV Ovarian Epithelial Cancer / Stage IV Ovarian Germ Cell Tumor / Stage IV Pancreatic Cancer / Stage IV Prostate Cancer / Stage IV Rectal Cancer / Stage IV Salivary Gland Cancer / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IV Squamous Cell Carcinoma of the Nasopharynx / Stage IV Squamous Cell Carcinoma of the Oropharynx / Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity / Stage IV Verrucous Carcinoma of the Larynx / Stage IV Verrucous Carcinoma of the Oral Cavity / Stage IVA Cervical Cancer / Stage IVB Cervical Cancer / Triple-Negative Breast Cancer (TNBC) / Unresectable Extrahepatic Bile Duct Cancer / Unresectable Gallbladder Cancer / Unspecified Adult Solid Tumor, Protocol Specific / Untreated Metastatic Squamous Neck Cancer With Occult Primary1
1CompletedTreatmentCancer, Breast / Malignant Lymphomas / Neoplasms / Prostatic Neoplasms1
1CompletedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
1CompletedTreatmentLeukemias / Malignant Lymphomas1
1CompletedTreatmentLeukemias / Malignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1CompletedTreatmentMalignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific5
1TerminatedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentLeukemias / Malignant Lymphomas1
2CompletedTreatmentCancer, Ovarian / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentExtensive Stage Small Cell Lung Cancer / Recurrent Small Cell Lung Cancer1
2CompletedTreatmentLymphoma, Large-Cell, Ki-1 / T-Cell Lymphomas1
2CompletedTreatmentMalignant Neoplasm of Pancreas1
2TerminatedTreatmentRecurrent Melanoma / Stage IV Melanoma1
2Unknown StatusTreatmentRenal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0592 mg/mLALOGPS
logP2.78ALOGPS
logP2.35ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)7.42ChemAxon
pKa (Strongest Basic)9.56ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area93.17 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity133.92 m3·mol-1ChemAxon
Polarizability51.41 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.608
Blood Brain Barrier-0.9237
Caco-2 permeable-0.5545
P-glycoprotein substrateSubstrate0.6904
P-glycoprotein inhibitor INon-inhibitor0.6076
P-glycoprotein inhibitor IINon-inhibitor0.7074
Renal organic cation transporterNon-inhibitor0.8762
CYP450 2C9 substrateNon-substrate0.7188
CYP450 2D6 substrateNon-substrate0.8225
CYP450 3A4 substrateSubstrate0.71
CYP450 1A2 substrateNon-inhibitor0.7904
CYP450 2C9 inhibitorNon-inhibitor0.8677
CYP450 2D6 inhibitorNon-inhibitor0.8983
CYP450 2C19 inhibitorNon-inhibitor0.825
CYP450 3A4 inhibitorNon-inhibitor0.7542
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7792
Ames testNon AMES toxic0.6281
CarcinogenicityNon-carcinogens0.8714
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5979 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9993
hERG inhibition (predictor II)Non-inhibitor0.8151
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Indolocarbazoles
Alternative Parents
Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Isoindolones / Indoles / Oxanes / Benzenoids / Pyrroles / Heteroaromatic compounds / Secondary carboxylic acid amides / Amino acids and derivatives
show 9 more
Substituents
Indolocarbazole / Pyrrolo[2,3-a]carbazole / Pyrroloindole / Isoindolone / Indole / Isoindoline / Isoindole or derivatives / Benzenoid / Oxane / Heteroaromatic compound
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB...
Gene Name
PDPK1
Uniprot ID
O15530
Uniprot Name
3-phosphoinositide-dependent protein kinase 1
Molecular Weight
63151.305 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Drug created on June 13, 2005 07:24 / Updated on November 09, 2017 03:06