Enzastaurin

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Enzastaurin
Accession Number
DB06486
Type
Small Molecule
Groups
Investigational
Description

Enzastaurin, an investigational, targeted, oral agent, will be evaluated at more than 100 sites worldwide for the treatment of relapsed glioblastoma multiforme (GBM), an aggressive and malignant form of brain cancer.

Structure
Thumb
Synonyms
Not Available
External IDs
LY-317615 / LY317615
Product Ingredients
IngredientUNIICASInChI Key
Enzastaurin HydrochlorideKX7K68Z2UH359017-79-1UUADYKVKJIMIPA-UHFFFAOYSA-N
Categories
UNII
UC96G28EQF
CAS number
170364-57-5
Weight
Average: 515.617
Monoisotopic: 515.232125194
Chemical Formula
C32H29N5O2
InChI Key
AXRCEOKUDYDWLF-UHFFFAOYSA-N
InChI
InChI=1S/C32H29N5O2/c1-35-19-25(23-9-2-4-11-27(23)35)29-30(32(39)34-31(29)38)26-20-37(28-12-5-3-10-24(26)28)22-13-16-36(17-14-22)18-21-8-6-7-15-33-21/h2-12,15,19-20,22H,13-14,16-18H2,1H3,(H,34,38,39)
IUPAC Name
3-(1-methyl-1H-indol-3-yl)-4-(1-{1-[(pyridin-2-yl)methyl]piperidin-4-yl}-1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione
SMILES
CN1C=C(C2=CC=CC=C12)C1=C(C(=O)NC1=O)C1=CN(C2CCN(CC3=CC=CC=N3)CC2)C2=CC=CC=C12

Pharmacology

Indication

Investigated for use/treatment in brain cancer, lymphoma (non-hodgkin's), and lung cancer.

Pharmacodynamics
Not Available
Mechanism of action

Enzastaurin is an oral serine-threonine kinase inhibitor that is designed to suppress tumor growth through multiple mechanisms. Preclinical data indicate it may reduce the cell's ability to reproduce (cell proliferation), increase the natural death of the tumor cells (apoptosis), and inhibit tumor- induced blood supply (angiogenesis). Enzastaurin has been shown to inhibit signaling through the PKC-B and PI3K/AKT pathways. These pathways have been shown to be activated in a wide variety of cancers. In addition to glioblastoma, enzastaurin is also being studied in multiple other tumor types, including non-Hodgkin's lymphoma, colorectal cancer, non-small cell lung cancer, pancreatic cancer, and mantle cell lymphoma.

TargetActionsOrganism
UProtein kinase C beta typeNot AvailableHumans
UAurora kinase BNot AvailableHumans
UAurora kinase ANot AvailableHumans
UCyclin-dependent kinase 15Not AvailableHumans
USerine/threonine-protein kinase Chk1Not AvailableHumans
USerine/threonine-protein kinase Chk2Not AvailableHumans
URAC-alpha serine/threonine-protein kinaseNot AvailableHumans
UPhosphatidylinositol 3-kinase regulatory subunit alphaNot AvailableHumans
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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
ChemSpider
153463
BindingDB
50128285
ChEBI
91368
ChEMBL
CHEMBL300138
Wikipedia
Enzastaurin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableMalignant Lymphomas / Tumors, Solid1
1CompletedOtherMalignant Lymphomas / Tumors, Solid1
1CompletedTreatmentAdults / Tumors, Solid1
1CompletedTreatmentBrain and Central Nervous System Tumors / Neuroblastomas1
1CompletedTreatmentLeukemia, Lymphocytic1
1CompletedTreatmentRecurrent Gliomas1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1Unknown StatusTreatmentBrain and Central Nervous System Tumors1
1, 2CompletedTreatmentGlioblastoma Multiforme (GBM) / Glioblastomas / Gliosarcoma1
1, 2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Solid Tumours1
2Active Not RecruitingTreatmentCancer, Breast1
2CompletedPreventionLung Cancers1
2CompletedTreatmentAbdominal wall neoplasm / Cancer of the Ovary / Fallopian Tube Neoplasms1
2CompletedTreatmentCancer of the Ovary / Carcinoma NOS / Neoplasms1
2CompletedTreatmentCancer of the Ovary / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCarcinoma, Colorectal / Colorectal Cancers / Colorectal Tumors1
2CompletedTreatmentColonic Neoplasms1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL)1
2CompletedTreatmentFollicular Lymphoma (FL)1
2CompletedTreatmentGlioblastoma Multiforme (GBM)1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancer Small Cell Lung Cancer (SCLC)1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentLymphoma, B-Cell / T-Cell Lymphomas1
2CompletedTreatmentLymphoma, Large Cell, Diffuse1
2CompletedTreatmentMalignancies / Neoplasms1
2CompletedTreatmentMalignant Gliomas1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMantle Cell Lymphoma (MCL)1
2CompletedTreatmentMetastatic Renal Cell Carcinoma1
2CompletedTreatmentMultiple Myeloma (MM) / Waldenström's Macroglobulinemia (WM)1
2CompletedTreatmentNeoplasms, Breast1
2CompletedTreatmentNeoplasms, Pancreatic1
2CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentProstate Cancer2
2CompletedTreatmentRecurrent Glioblastoma1
2Not Yet RecruitingTreatmentGlioblastomas1
2TerminatedTreatmentCancer, Breast1
2WithdrawnTreatmentLung Cancers1
2WithdrawnTreatmentProstate Cancer1
3CompletedPreventionNon Hodgkin Lymphoma (NHL)1
3CompletedTreatmentGlioblastomas1
3RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1

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 Solubility0.00903 mg/mLALOGPS
logP4.86ALOGPS
logP3.96ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)9.71ChemAxon
pKa (Strongest Basic)7.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.16 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity151.61 m3·mol-1ChemAxon
Polarizability56.74 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 n-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
N-alkylindoles
Direct Parent
N-alkylindoles
Alternative Parents
Indoles / 2-pyridylmethylamines / Aralkylamines / Maleimides / Benzenoids / Piperidines / N-methylpyrroles / Heteroaromatic compounds / Dicarboximides / Pyrrolines
show 8 more
Substituents
N-alkylindole / Indole / 2-pyridylmethylamine / Maleimide / Aralkylamine / N-methylpyrrole / Piperidine / Pyridine / Substituted pyrrole / Benzenoid
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosom...
Gene Name
PRKCB
Uniprot ID
P05771
Uniprot Name
Protein kinase C beta type
Molecular Weight
76868.45 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in...
Gene Name
AURKB
Uniprot ID
Q96GD4
Uniprot Name
Aurora kinase B
Molecular Weight
39310.195 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role i...
Gene Name
AURKA
Uniprot ID
O14965
Uniprot Name
Aurora kinase A
Molecular Weight
45809.03 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at 'Thr-34'.
Gene Name
CDK15
Uniprot ID
Q96Q40
Uniprot Name
Cyclin-dependent kinase 15
Molecular Weight
49022.64 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also nega...
Gene Name
CHEK1
Uniprot ID
O14757
Uniprot Name
Serine/threonine-protein kinase Chk1
Molecular Weight
54433.115 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also...
Gene Name
CHEK2
Uniprot ID
O96017
Uniprot Name
Serine/threonine-protein kinase Chk2
Molecular Weight
60914.26 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, ...
Gene Name
AKT1
Uniprot ID
P31749
Uniprot Name
RAC-alpha serine/threonine-protein kinase
Molecular Weight
55686.035 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transmembrane receptor protein tyrosine kinase adaptor activity
Specific Function
Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for t...
Gene Name
PIK3R1
Uniprot ID
P27986
Uniprot Name
Phosphatidylinositol 3-kinase regulatory subunit alpha
Molecular Weight
83597.675 Da

Drug created on March 19, 2008 10:34 / Updated on June 04, 2019 06:24