GZD824 Dimesylate(HQP1351)

Catalog No.S7194

GZD824 Dimesylate(HQP1351) Chemical Structure

Molecular Weight(MW): 724.77

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.

Size Price Stock Quantity  
USD 170 In stock
USD 570 In stock
Bulk Discount
Bulk Inquiry

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Cited by 2 Publications

1 Customer Review

  • B. Western blot analysis of phosphorylated Akt, S6 and CrkL in T-ALL cell lines treated for 4 h with 2 μM Imatinib or Nilotinib or 0.1 μM GZD824. Twenty-five μg of protein were blotted to each lane. β-Actin documented equal lane loading. Imatinib, Nilotinib and GZD824 were abbreviated in IMA, NIL and GZD.

    Oncotarget, 2016, 7(48):79842-79853. GZD824 Dimesylate(HQP1351) purchased from Selleck.

Purity & Quality Control

Choose Selective Bcr-Abl Inhibitors

Biological Activity

Description 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.
Targets
Abl (Q252H) [1] Abl (E255K) [1] Abl (M351T) [1] Abl [1] Abl (H396P) [1]
0.15 nM 0.27 nM 0.29 nM 0.34 nM 0.35 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]
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]

Protocol

Kinase Assay:[1]
+ Expand

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.
Cell Research:[1]
+ Expand
  • Cell lines: Ba/F3 cells expressing wildtype and mutant Bcr-Abl
  • Concentrations: 0-50 μM
  • Incubation Time: 72 hours
  • Method: Cells 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Mice xenograft or allograft tumor models using K562 and transformed Ba/F3 cells expressing native Bcr-Abl or Bcr-Abl mutants.
  • Formulation: 1% DMSO, 22.5% Cremophor, 7.5% ethanol, and 69% normal saline
  • Dosages: ~20 mg/kg
  • Administration: oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (137.97 mM)
Water 100 mg/mL (137.97 mM)
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
Saline
For best results, use promptly after mixing. 		20 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 724.77
Formula

C29H27F3N6O.2CH4O3S
CAS No. 1421783-64-3
Storage powder
in solvent
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03883100 Not yet recruiting Chronic Myeloid Leukemia - Accelerated Phase Ascentage Pharma Group Inc. March 2019 Phase 2
NCT03882281 Not yet recruiting Chronic Myeloid Leukemia Chronic Phase Ascentage Pharma Group Inc. March 2019 Phase 1
NCT03883087 Not yet recruiting Chronic Myeloid Leukemia Chronic Phase Ascentage Pharma Group Inc. March 2019 Phase 2
NCT03883100 Not yet recruiting Chronic Myeloid Leukemia - Accelerated Phase Ascentage Pharma Group Inc. March 2019 Phase 2
NCT03882281 Not yet recruiting Chronic Myeloid Leukemia Chronic Phase Ascentage Pharma Group Inc. March 2019 Phase 1
NCT03883087 Not yet recruiting Chronic Myeloid Leukemia Chronic Phase Ascentage Pharma Group Inc. March 2019 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field
selleck catalog

Bcr-Abl Signaling Pathway Map

Related Bcr-Abl Products0

  • PX-478 2HCl New

    PX-478 2HCl is an orally active, and selective hypoxia-inducible factor-1α (HIF-1α) inhibitor. Phase 1.

  • Defactinib (VS-6063, PF-04554878) New

    Defactinib (VS-6063, PF-04554878) is a selective, and orally active FAK inhibitor. Phase 2.

  • SU6656 New

    SU 6656 is a selective Src family kinase inhibitor with IC50 of 280 nM, 20 nM, 130 nM, and 170 nM for Src, Yes, Lyn, and Fyn, respectively.

  • Imatinib Mesylate (STI571)

    Imatinib Mesylate (STI571) is an orally bioavailability mesylate salt of Imatinib, which is a multi-target inhibitor of v-Abl, c-Kit and PDGFR with IC50 of 0.6 μM, 0.1 μM and 0.1 μM in cell-free or cell-based assays, respectively.

  • Ponatinib (AP24534)

    Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM in cell-free assays, respectively.

  • Nilotinib (AMN-107)

    Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells.

    Features:A selective inhibitor of native and mutant Bcr-Abl.

  • Bafetinib (INNO-406)

    Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM in cell-free assays, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit. Phase 2.

    Features:Dual Bcr-Abl/Lyn inhibitor.

  • Degrasyn (WP1130)

    Degrasyn (WP1130) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT).

    Features:WP1130 has an advantage over imatinib mesylate in that its activity is not inhibited by a variety of Abl kinase mutations, including T315I.

  • Rebastinib (DCC-2036)

    Rebastinib (DCC-2036) is a conformational control Bcr-Abl inhibitor for Abl1(WT) and Abl1(T315I) with IC50 of 0.8 nM and 4 nM, also inhibits SRC, LYN, FGR, HCK, KDR, FLT3, and Tie-2, and low activity to seen towards c-Kit. Phase 1.

    Features:A conformational control inhibitor of Abl1 and T315I Abl1.

  • GNF-2

    GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl, shows no activity to Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells.

Tags: buy GZD824 Dimesylate(HQP1351) | GZD824 Dimesylate(HQP1351) supplier | purchase GZD824 Dimesylate(HQP1351) | GZD824 Dimesylate(HQP1351) cost | GZD824 Dimesylate(HQP1351) manufacturer | order GZD824 Dimesylate(HQP1351) | GZD824 Dimesylate(HQP1351) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID