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

Details

Stereochemistry ACHIRAL
Molecular Formula C29H27F3N6O
Molecular Weight 532.5606
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of OLVEREMBATINIB

SMILES

Cc1ccc(cc1C#Cc2cc3c[nH]nc3nc2)C(=O)Nc4ccc(CN5CCN(C)CC5)c(c4)C(F)(F)F

InChI

InChIKey=TZKBVRDEOITLRB-UHFFFAOYSA-N
InChI=1S/C29H27F3N6O/c1-19-3-5-22(14-21(19)6-4-20-13-24-17-34-36-27(24)33-16-20)28(39)35-25-8-7-23(26(15-25)29(30,31)32)18-38-11-9-37(2)10-12-38/h3,5,7-8,13-17H,9-12,18H2,1-2H3,(H,35,39)(H,33,34,36)

HIDE SMILES / InChI

Molecular Formula C29H27F3N6O
Molecular Weight 532.5606
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

GZD824 is a novel orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 of 0.34 nM and 0.68 nM, respectively. In vivo efficacy studies in mouse xenograft or allograft models of human leukemia demonstrated that GZD824 successfully suppressed the growth of tumors driven by native Bcr-Abl, Bcr-Abl T315I, Bcr-Abl G250E, Bcr-Abl Q252H, Bcr-Abl E255K and Bcr-Abl F317L. GZD824 also provided a significant survival benefit leukemia model mice allografted with luciferase-expressing Ba/F3 cells driven by the mutant Bcr-Abl T315I kinase. The potential for compound GZD824 to overcome all of the Bcr-Abl mutations that result in clinically acquired resistance to imatinib indicates that this novel Bcr-Abl inhibitor is a promising lead candidate for further development. GZD824 has also being shown to suppresses pre-B ALL cells through inhibition of the SRC kinase and PI3K/AKT pathways and may be a potential therapeutic agent for the management of pre-B ALL.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.34 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib.
2013 Feb 14
Patents

Patents

Sample Use Guides

GZD824 dose-dependently inhibited the growth of the K562 tumor xenograft when administrated once daily for 14 consecutive days via oral gavage. A significant reduction in tumor size was observed after only 2 days of treatment at doses of 2, 5 and 10 mg/kg/day
Route of Administration: Oral
GZD824 strongly inhibited the proliferation of Ba/F3 cells that stably expressed the most refractory Bcr-Abl T315I mutant, with an IC50 value of 7.1 nM. GZD824 strongly inhibited the growth of leukemia cells positively expressing Bcr-Abl, including K562 and Ku812 human CML cells as well as SUP-B15 human acute lymphocyte leukemia (ALL) cells, with IC50 values of 0.21, 0.13 and 2.5 nM, respectively.
Substance Class Chemical
Created
by admin
on Sat Jun 26 02:43:19 UTC 2021
Edited
by admin
on Sat Jun 26 02:43:19 UTC 2021
Record UNII
KV1M7Q3CBP
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OLVEREMBATINIB
INN  
Official Name English
BENZAMIDE, 4-METHYL-N-(4-((4-METHYL-1-PIPERAZINYL)METHYL)-3-(TRIFLUOROMETHYL)PHENYL)-3-(2-(1H-PYRAZOLO(3,4-B)PYRIDIN-5-YL)ETHYNYL)-
Common Name English
HQP1351
Code English
GZD-824
Code English
OLVEREMBATINIB [WHO-DD]
Common Name English
HQP-1351 FREE BASE
Code English
OLVEREMBATINIB [INN]
Common Name English
D-824
Code English
4-METHYL-N-(4-((4-METHYL-1-PIPERAZINYL)METHYL)-3-(TRIFLUOROMETHYL)PHENYL)-3-(2-(1H-PYRAZOLO(3,4-B)PYRIDIN-5-YL)ETHYNYL)BENZAMIDE
Systematic Name English
HQP-1351
Code English
HQP1351 FREE BASE
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 735620
Created by admin on Sat Jun 26 02:43:19 UTC 2021 , Edited by admin on Sat Jun 26 02:43:19 UTC 2021
Code System Code Type Description
PUBCHEM
51038269
Created by admin on Sat Jun 26 02:43:19 UTC 2021 , Edited by admin on Sat Jun 26 02:43:19 UTC 2021
PRIMARY
CAS
1257628-77-5
Created by admin on Sat Jun 26 02:43:19 UTC 2021 , Edited by admin on Sat Jun 26 02:43:19 UTC 2021
PRIMARY
NCI_THESAURUS
C165549
Created by admin on Sat Jun 26 02:43:19 UTC 2021 , Edited by admin on Sat Jun 26 02:43:19 UTC 2021
PRIMARY
FDA UNII
KV1M7Q3CBP
Created by admin on Sat Jun 26 02:43:19 UTC 2021 , Edited by admin on Sat Jun 26 02:43:19 UTC 2021
PRIMARY
INN
11221
Created by admin on Sat Jun 26 02:43:19 UTC 2021 , Edited by admin on Sat Jun 26 02:43:19 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
nonphosphorylated form
Kd
TARGET -> INHIBITOR
nonphosphorylated form
Kd
Related Record Type Details
ACTIVE MOIETY