Olverembatinib Dimesylate (GZD824)

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Size	Price	Stock
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500mg	$1550	Check With Us
1g	$2325	Check With Us

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Cat #: V0675 CAS #: 1421783-64-3 Purity ≥ 98%

Description: Olverembatinib Dimesylate (GZD-824; HQP-1351; trade name in China: Nailike), the dimesylate salt of GZD824 (HQP1351), is a novel, potent, orally bioavailable Bcr-Abl inhibitor with potential antineoplastic activity. As of November 2021, Olverembatinib has been approved in China for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. It inhibits Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50s of 0.34 nM and 0.68 nM, respectively.

References: [1]. Ren X, Pan X, Zhang Z, 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. J Med Chem. 2013 Feb 14;56(3):879-94.

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Physicochemical and Storage Information
Protocol
Related Biological Data
Stock Solution Preparation
Quality Control Documentation

Molecular Weight (MW)	724.77
Molecular Formula	C29H27F3N6O.2CH4O3S
CAS No.	1421783-64-3
Storage	-20℃ for 3 years in powder formr
Storage	-80℃ for 2 years in solvent
Solubility In Vitro	DMSO: 100 mg/mL (137.9 mM)r
	Water: 100 mg/mL (137.9 mM)r
	Ethanol:<1 mg/mL
Solubility In Vivo	Saline: 20 mg/mL
SMILES Code	CN1CCN(Cc2ccc(NC(=O)c3ccc(C)c(c3)C#Cc4cnc5[nH]ncc5c4)cc2C(F)(F)F)CC1.CS(=O)(=O)O.CS(=O)(=O)O
Synonyms	GZD824 Dimesylate; Olverembatinib Dimesylate; GZD-824; HQP-1351; GZD 824 Dimesylate; GZD-824 Dimesylate; GZD824; HQP1351; GZD 824; GZD-824

Protocol	In Vitro	In vitro activity: 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. Kinase Assay: 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. Cell Assay: Cells (Ba/F3 cells expressing wildtype and mutant Bcr-Abl) in the logarithmic phase are plated in 96-well culture dishes. Twenty-four hours later, cells are treated with the corresponding compounds or vehicle control at the indicated concentration for 72 h. CCK-8 is added into the 96-well plates (10 μL/well) and incubated with the cells for 3 h. OD450 and OD650 are determined by a microplate reader. Absorbance rate (A) for each well is calculated as OD450 – OD650. The cell viability rate for each well is calculated as V% = (As – Ac)/(Ab – Ac) × 100%, and the data were further analyzed using Graphpad Prism5. The data are the mean value of the three experiments. As is the absorbance rate of the test compound well, Ac is the absorbance rate of the well without either cell or test compound, and Ab is the absorbance rate of the well with cell and vehicle control.
	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.
	Animal model	Mice xenograft or allograft tumor models using K562 and transformed Ba/F3 cells expressing native Bcr-Abl or Bcr-Abl mutants
	Formulation	Dissolved in 1% DMSO, 22.5% Cremophor, 7.5% ethanol, and 69% normal saline
	Dosages	20 mg/kg ; p.o.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Preparing Stock Solutions

Solvent volume to be added	Mass (the weight of a compound)
Mother liquor concentration	1mg	5mg	10mg	20mg
1mM	1.3797 mL	6.8987 mL	13.7975 mL	27.5950 mL
5mM	0.2759 mL	1.3797 mL	2.7595 mL	5.5190 mL
10mM	0.1380 mL	0.6899 mL	1.3797 mL	2.7595 mL
20mM	0.0690 mL	0.3449 mL	0.6899 mL	1.3797 mL

Quality Control Documentation	Select Batch Purity ≥ 98% COA MSDS NMR HPLC

The molarity calculator equation

Mass(g) = Concentration(mol/L) × Volume(L) × Molecular Weight(g/mol)

Mass

Concentration

Volume

Molecular Weight*

The dilution calculator equation

Concentration_(start) × Volume_(start) = Concentration_(final) × Volume_(final)

This equation is commonly abbreviated as: C₁ V₁ = C₂ V₂

Concentration_(start)

Volume_(start)

Concentration_(final)

Volume_(final)

Step One: Enter information below

Dosage mg/kg Average weight of animals g Dosing volume per animal µL Number of animals

Step Two: Enter the in vivo formulation

%DMSO + % + %Tween 80 + %ddH₂O

Calculation Results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in µL DMSO(Master liquid concentration mg/mL) ,Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation: Take µL DMSO master liquid, next add µL PEG300, mix and clarify, next add µL Tween 80,mix and clarify, next add µL ddH₂O,mix and clarify.

Note:

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.