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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=C2C(N)=O)N1C3=NC4=C(COCC4)C(NCC5=CC=CC=C5)=N3

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

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
11.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
CB-5083 (2.5 uM) induced CHOP protein in A549 cells