Home Angiogenesis Bcr-Abl inhibitor Olverembatinib (GZD824) dimesylate

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Olverembatinib (GZD824) dimesylate Bcr-Abl inhibitor

Cat.No.S7194

Olverembatinib (GZD824) dimesylate 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.
Olverembatinib (GZD824) dimesylate Bcr-Abl inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 724.77

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Quality Control

Batch: S719401 DMSO]100 mg/mL]false]Water]100 mg/mL]false]Ethanol]Insoluble]false Purity: 99.83%
99.83

Chemical Information, Storage & Stability

Molecular Weight 724.77 Formula

C29H27F3N6O.2CH4O3S

 Storage (From the date of receipt)
CAS No. 1421783-64-3 Download SDF Storage of Stock Solutions

Synonyms HQP1351 dimesylate Smiles CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CC5=C(NN=C5)N=C4.CS(=O)(=O)O.CS(=O)(=O)O

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (137.97 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : 100 mg/mL

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
Abl (Q252H) [1]
0.15 nM
Abl (E255K) [1]
0.27 nM
Abl (M351T) [1]
0.29 nM
Abl [1]
0.34 nM
Abl (H396P) [1]
0.35 nM
Abl (Y253F) [1]
0.35 nM
Abl (T315I) [1]
0.68 nM
Abl (G250E) [1]
0.71 nM
In vitro
GZD824 potently inhibits the growth of Ba/F3 cells expressing wildtype Bcr-Abl with IC50 of 1.0 nM. Highly consistent with biochemical kinase inhibition and tight protein binding affinity, GZD824 also strongly inhibits the proliferation of Ba/F3 cells expressing Bcr-AblT315I mutant and 14 other resistance-relevant Bcr-Abl mutants. In addition, GZD824 efficiently suppresses the activation of Bcr-Abl as well as downstream Crkl and STAT5 in a concentration-dependent manner in K562 CML cells. [1]
Kinase Assay
FRET-Based Z′-Lyte Assay Detecting Peptide Substrate Phosphorylation
The kinases ABL1, ABL1(E255K), ABL1 (G250E), ABL1(T315I), and ABL1(Y253F) are P3049, PV3864, PV3865, PV3866, and PV3863 are full-length human recombinant protein expressed in insect cells and histidine-tagged. Inhibition activities of inhibitors against Abl1 and its mutants are performed in 384-well plates using the FRET-based Z′-Lyte assay system. Briefly, the kinase substrate is diluted into 5 μL of kinase reaction buffer; and the kinase is added. Compounds (10 nL) with indicated concentrations are then delivered to the reaction by using Echo liquid handler, and the mixture is incubated for 30 min at room temperature. Then 5 μL of 2X ATP solution is added to initiate the reaction, and the mixture is further incubated for 2 h at room temperature. The resulting reactions contains 10 μM (for wild-type Abl1, and mutants Y253F, Q252H, M351T, and H396P) or 5 μM (for mutants E255K, G250E, T315I) of ATP, 2 μM of Tyr2 Peptide substrate in 50 mM HEPES (PH 7.5), 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA, 0.0247 μg/mL Abl1, and inhibitors as appropriate. Then, 5 μL of development reagent is added, and the mixture is incubated for 2 h at room temperature before 5 μL of stop solution is added. Fluorescence signal ratio of 445 nm (Coumarin)/520 nm (fluorescin) is examined on an EnVision Multilabel Reader. The data are analyzed using Graphpad Prism5. The data are the mean value of three experiments.
In vivo
GZD824, at doses of 5 and 10 mg/kg/day, dose-dependently inhibits the tumor growth in the K562 tumor xenograft and the Ku812 xenograft model without mortality or significant body loss. Besides, GZD824 (20 mg/kg/day) suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-AblWT and Bcr-AblT315I. [1]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03594422 Recruiting
Gastrointestinal Stromal Tumor (GIST)|Solid Tumor Adult
Ascentage Pharma Group Inc.|HealthQuest Pharma Inc.
 July 11 2018 Phase 1

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