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Details

Stereochemistry ACHIRAL
Molecular Formula C25H22N6O2
Molecular Weight 438.4812
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SOTRASTAURIN

SMILES

CN1CCN(CC1)C2=NC(C3=C(C(=O)NC3=O)C4=CNC5=C4C=CC=C5)=C6C=CC=CC6=N2

InChI

InChIKey=OAVGBZOFDPFGPJ-UHFFFAOYSA-N
InChI=1S/C25H22N6O2/c1-30-10-12-31(13-11-30)25-27-19-9-5-3-7-16(19)22(28-25)21-20(23(32)29-24(21)33)17-14-26-18-8-4-2-6-15(17)18/h2-9,14,26H,10-13H2,1H3,(H,29,32,33)

HIDE SMILES / InChI

Molecular Formula C25H22N6O2
Molecular Weight 438.4812
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Sotrastaurin, an orally-active, first-in-class immunomodulator, is under development by Novartis for the treatment of uveal melanoma and diffuse-large B-cell lymphoma. Sotrastaurin is a low molecular mass synthetic compound that potently inhibits the PKC α, β and the θ isoforms resulting in selective NF-κB inactivation. Sotrastaurin is a potent and selective pan-PKC inhibitor, mostly for PKCθ with Ki of 0.22 nM in a cell-free assay. Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents. PKC, a family of serine/threonine protein kinases overexpressed in certain types of cancer cells, is involved in cell differentiation, mitogenesis, inflammation, and the activation and survival of lymphocytes. Sotrastaurin is currently in phase II trials by Novartis for the treatment of large B-cell lymphoma and uveal melanoma. Sotrastaurin was in Phase II of clinical development for the prevention of acute rejection after solid organ transplantation and psoriasis, but this reseach had being discontinued.

CNS Activity

Curator's Comment: Sotrastaurin does not penetrate the monkey blood-brain barrier.

Originator

Curator's Comment: # Novartis; Ohio State University

Approval Year

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Sotrastaurin, a protein kinase C inhibitor for the prevention of transplant rejection and treatment of psoriasis.
2009 Nov
Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes.
2009 Oct 22
The potent protein kinase C-selective inhibitor AEB071 (sotrastaurin) represents a new class of immunosuppressive agents affecting early T-cell activation.
2009 Sep
Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients.
2010 Mar
Novel immunosuppressive agents in kidney transplantation.
2010 May
Docetaxel Facilitates Endothelial Dysfunction through Oxidative Stress via Modulation of Protein Kinase C Beta: The Protective Effects of Sotrastaurin.
2015 May
Patents

Patents

Sample Use Guides

Uveal melanoma treatment: oral, 100-400 mg twice daily
Route of Administration: Oral
Sotrastaurin (< 10uM) treatment effectively abrogated at low nanomolar concentration markers of early T-cell activation, such as interleukin-2 secretion and CD25 expression, in primary human and mouse T cells. Sotrastaurin (200 nM) inhibits the CD3/CD28 antibody- and alloantigen-induced T-cell proliferation responses in the absence of nonspecific antiproliferative effects. Sotrastaurin (<3 uM) markedly inhibits lymphocyte function-associated antigen-1-mediated T-cell adhesion.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:38:06 GMT 2023
Edited
by admin
on Fri Dec 15 16:38:06 GMT 2023
Record UNII
7I279E1NZ8
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SOTRASTAURIN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
Sotrastaurin [WHO-DD]
Common Name English
sotrastaurin [INN]
Common Name English
AEB-071
Code English
3-(1H-Indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-1H-pyrrole-2,5-dione
Systematic Name English
1H-PYRROLE-2,5-DIONE, 3-(1H-INDOL-3-YL)-4-(2-(4-METHYL-1-PIPERAZINYL)-4-QUINAZOLINYL)-
Systematic Name English
SOTRASTAURIN [USAN]
Common Name English
AEB071
Code English
Classification Tree Code System Code
NCI_THESAURUS C2089
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL565612
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
FDA UNII
7I279E1NZ8
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
EVMPD
SUB124612
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
USAN
WW-26
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
SMS_ID
100000145826
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
MESH
C543528
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
INN
8893
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
NCI_THESAURUS
C80630
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
PUBCHEM
10296883
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
CAS
425637-18-9
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
DRUG BANK
DB12369
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
CHEBI
90531
Created by admin on Fri Dec 15 16:38:06 GMT 2023 , Edited by admin on Fri Dec 15 16:38:06 GMT 2023
PRIMARY
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ACTIVE MOIETY