U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C24H23N5O2
Molecular Weight 413.4717
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CB-5083

SMILES

CC1=CC2=C(C=CC=C2N1C3=NC(NCC4=CC=CC=C4)=C5COCCC5=N3)C(N)=O

InChI

InChIKey=RDALZZCKQFLGJP-UHFFFAOYSA-N
InChI=1S/C24H23N5O2/c1-15-12-18-17(22(25)30)8-5-9-21(18)29(15)24-27-20-10-11-31-14-19(20)23(28-24)26-13-16-6-3-2-4-7-16/h2-9,12H,10-11,13-14H2,1H3,(H2,25,30)(H,26,27,28)

HIDE SMILES / InChI

Molecular Formula C24H23N5O2
Molecular Weight 413.4717
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.fasebj.org/content/29/1_Supplement/LB137.short | https://www.ncbi.nlm.nih.gov/pubmed/26555175

CB-5083 is a novel first in class, potent orally bio-available p97 inhibitor that disrupts cellular protein homeostasis and demonstrates anti-tumor activity in solid and hematological models. CB-5083 causes rapid and sustained accumulation of poly-ubiquitin in tumor xenografts after a single administration. CB-5083 showed activity to inhibit tumor growth in multiple rodent models of human cancer. Furthermore, CB-5083 appears to exhibit greater potency over current proteasome inhibitors that further validate targeting p97 and protein homeostasis in the treatment of cancer. CB-5083 is a potent inhibitor of endoplasmic reticulum associated degradation and induces a lethal unfodled protein response. CB-5083 recently began Phase 1 testing in relapsed/refractory or refractory multiple myeloma, and advanced solid tumors.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083).
2015 Dec 24
Patents

Patents

Sample Use Guides

Mice: In mice bearing human HCT 116 colon tumor xenografts, CB-5083 (75 mg/kg, p.o.) significantly inhibits tumor growth. In mice bearing established human AMO-1 multiple myeloma and A549 lung carcinoma tumor xenografts, CB-5083 (100 mg/kg, p.o.) results in significant tumor growth inhibition.
Route of Administration: Oral
CB-5083 (2.5 uM) induced CHOP protein in A549 cells
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:27:04 GMT 2023
Edited
by admin
on Sat Dec 16 09:27:04 GMT 2023
Record UNII
591IV6UL6J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CB-5083
Common Name English
CB 5083 [WHO-DD]
Common Name English
1-(7,8-DIHYDRO-4-((PHENYLMETHYL)AMINO)-5H-PYRANO(4,3-D)PYRIMIDIN-2-YL)-2-METHYL-1H-INDOLE-4-CARBOXAMIDE
Systematic Name English
1H-INDOLE-4-CARBOXAMIDE, 1-(7,8-DIHYDRO-4-((PHENYLMETHYL)AMINO)-5H-PYRANO(4,3-D)PYRIMIDIN-2-YL)-2-METHYL-
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 483815
Created by admin on Sat Dec 16 09:27:04 GMT 2023 , Edited by admin on Sat Dec 16 09:27:04 GMT 2023
Code System Code Type Description
FDA UNII
591IV6UL6J
Created by admin on Sat Dec 16 09:27:04 GMT 2023 , Edited by admin on Sat Dec 16 09:27:04 GMT 2023
PRIMARY
NCI_THESAURUS
C118287
Created by admin on Sat Dec 16 09:27:04 GMT 2023 , Edited by admin on Sat Dec 16 09:27:04 GMT 2023
PRIMARY
PUBCHEM
73051434
Created by admin on Sat Dec 16 09:27:04 GMT 2023 , Edited by admin on Sat Dec 16 09:27:04 GMT 2023
PRIMARY
EPA CompTox
DTXSID801022542
Created by admin on Sat Dec 16 09:27:04 GMT 2023 , Edited by admin on Sat Dec 16 09:27:04 GMT 2023
PRIMARY
CAS
1542705-92-9
Created by admin on Sat Dec 16 09:27:04 GMT 2023 , Edited by admin on Sat Dec 16 09:27:04 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY