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Réactifs et instruments pour l'immunologie, la biologie cellulaire et la biologie moléculaire.

Olverembatinib [1257628-77-5]

Imprimer

Référence HY-15666-5mg

Conditionnement : 5mg

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Marque : MedChemExpress

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Description

Olverembatinib (GZD824) is a potent and orally active pan-Bcr-Abl inhibitor. Olverembatinib potently inhibits a broad spectrum of Bcr-Abl mutants. Olverembatinib strongly inhibits native Bcr-Abl and Bcr-Abl^T315I with IC₅₀s of 0.34 nM and 0.68 nM, respectively. Olverembatinib has antitumor activity^[1]. Olverembatinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

IC₅₀ & Target

IC50: 0.68 nM (Bcr-Abl^T315I), 0.27 nM (Bcr-Abl^E255K) , 0.71 nM (Bcr-Abl^G250E) , 0.15 nM (Bcr-Abl^Q252H), 0.35 nM (Bcr-Abl^H396P), 0.29 nM (Bcr-Abl^M351T), 0.35 nM (Bcr-Abl^Y253F), Bcr-Abl^F317L^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	IC₅₀	0.0002 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL M351T mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL M351T mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.001 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL F486S mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL F486S mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.001 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing wild type BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing wild type BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0023 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E359V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E359V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0026 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E355G mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E355G mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0027 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL F317L mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL F317L mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.003 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL Y253H mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL Y253H mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0035 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E255K mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E255K mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.004 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL F317V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL F317V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0055 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL H396R mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL H396R mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.006 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL G250E mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL G250E mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.006 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL Q252H mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL Q252H mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0071 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL T315I mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL T315I mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0073 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL L248V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL L248V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.0081 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E255V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL E255V mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.011 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL Y253F mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL Y253F mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.17 μM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
BaF3	IC₅₀	0.2 nM Compound: 10a, GZD824	Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL M351T mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against mouse BA/F3 cells expressing BCR-ABL M351T mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
HL-60	IC₅₀	348.9 nM Compound: 10a, GZD824	Cytotoxicity against human HL60 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against human HL60 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
K562	IC₅₀	0.2 nM Compound: 10a, GZD824	Cytotoxicity against human K562 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against human K562 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
K562	IC₅₀	4.5 nM Compound: 10a, GZD824	Cytotoxicity against imatinib-resistant human K562 cells expressing BCR-ABL Q252H mutant assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against imatinib-resistant human K562 cells expressing BCR-ABL Q252H mutant assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
KU812 cell line	IC₅₀	0.13 nM Compound: 10a, GZD824	Cytotoxicity against human KU812 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against human KU812 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
MOLT-4	IC₅₀	26.3 nM Compound: 10a, GZD824	Cytotoxicity against human MOLT4 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against human MOLT4 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
SUP-B15	IC₅₀	2.5 nM Compound: 10a, GZD824	Cytotoxicity against human SUP-B15 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against human SUP-B15 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]
U-937	IC₅₀	390.2 nM Compound: 10a, GZD824	Cytotoxicity against human U937 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay Cytotoxicity against human U937 cells expressing BCR-ABL assessed as growth inhibition after 72 hrs by CCK-8 assay	[PMID: 23301703]

In Vitro

Olverembatinib shows antiproliferative activity in stably transformed Ba/F3 cells whose growth was driven by native Bcr-Abl or Bcr-Abl mutants^[1].
Olverembatinib selectively and potently inhibits the proliferation of Bcr-Abl-positive leukemia cells^[1].
Olverembatinib inhibits Bcr-Abl signaling in K562 (1-20 nM; 4.0 hours) and Ba/F3 stable cell lines expressing native Bcr-Abl (0.1-100 nM; 4.0 hours) or Bcr-Abl^T315I(0.1-100 nM; 4.0 hours)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:	K562 cells
Concentration:	1 nM, 2 nM, 5 nM, 10 nM, 20nM
Incubation Time:	4.0 hours
Result:	Inhibited Bcr-Abl signaling in K562 cell lines.

In Vivo

Olverembatinib suppresses tumor growth in mice bearing allografted Ba/F3 cells expressing Bcr-Abl ^WT^[1].
Olverembatinib (1-20 mg/kg; i.g.; daily; for 10 days) significantly increases the median survival of the mice bearing allografted Ba/F3 cells expressing Bcr-Abl^T315I^[1].
Olverembatinib exhibits a good oral bioavailability (rat 48.7%) and C_max (rat 390.5 μg/L) following oral administration (rat; 25 mg/kg)^[1].
Olverembatinib exhibits terminal elimination half-lives (rat 5.6 h) due to high plasma clearance (rat 1.7 L/h/kg) following intravenous administration (rat 5 mg/kg)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	SCID nude mice, bearing allografted Ba/F3 cells expressing Bcr-Abl^T315I^[1]
Dosage:	1 mg/kg, 2 mg/kg, 5.0 mg/kg, 10 mg/kg, 20 mg/kg
Administration:	Oral gavage, daily, for 10 days
Result:	Efficiently prolonged animal survival in an allograft leukemia tumor model.

Animal Model:	Rats^[1]
Dosage:	5 mg/kg for i.v.; 25 mg/kg for oral (Pharmacokinetic Analysis)
Administration:	Intravenous injection and oral administration
Result:	Oral bioavailability (48.7%), C_max (390.5 μg/L), T_1/2 (5.6 h).

Essai clinique

Masse moléculaire

532.56

Formule

C₂₉H₂₇F₃N₆O

CAS No.

1257628-77-5

Appearance

Solid

Color

Off-white to yellow

SMILES

O=C(NC1=CC=C(CN2CCN(C)CC2)C(C(F)(F)F)=C1)C3=CC=C(C)C(C#CC4=CN=C(NN=C5)C5=C4)=C3

Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvant et solubilité

In Vitro:

DMSO : 41.67 mg/mL (78.24 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.8777 mL	9.3886 mL	18.7772 mL
5 mM	0.3755 mL	1.8777 mL	3.7554 mL
10 mM	0.1878 mL	0.9389 mL	1.8777 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.75 mg/mL (5.16 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.75 mg/mL (5.16 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.75 mg/mL (5.16 mM); Clear solution

This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 900 μL Corn oil, and mix evenly.

Pureté et documentation

Purity: 99.47%

Fiche technique (277 KB) SDS (393 KB)

COA (247 KB) LCMS (93 KB)

Instruction de manipulation (2659 KB)

Références

[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. [Content Brief]

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Référence HY-15666-5mg

Contactez votre distributeur local :

Marque : MedChemExpress

Contactez votre distributeur local :

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