OLVEREMBATINIB

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H27F3N6O
Molecular Weight	532.5595
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCN(CC2=CC=C(NC(=O)C3=CC=C(C)C(=C3)C#CC4=CC5=C(NN=C5)N=C4)C=C2C(F)(F)F)CC1

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	532.5595
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23301703

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23301703	Inhibitor 8504		0.34 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic myelogenous leukemia 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23301703	Primary		Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
8.72 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5.26 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
12.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
237 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
276 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
125 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
302 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
32.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		OLVEREMBATINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
32.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.05% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
0.07% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36582520/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		OLVEREMBATINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

PubMed

Title	Date	PubMed
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.	2013-02-14	23301703

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Wed Apr 02 01:59:52 GMT 2025` Edited by `admin` on `Wed Apr 02 01:59:52 GMT 2025`
Record UNII	KV1M7Q3CBP
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GZD-824

Preferred Name

English

OLVEREMBATINIB

Official Name

English

Olverembatinib [WHO-DD]

Common 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)-

Systematic Name

English

HQP1351

Code

English

olverembatinib [INN]

Common Name

English

OLVEREMBATINIB [USAN]

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

Classification Tree Code System Code

FDA ORPHAN DRUG

903622