GNF-5

Catalog No.S7526 Batch:S752601

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Technical Data

Formula

C20H17F3N4O3
Molecular Weight 418.37 CAS No. 778277-15-9
Solubility (25°C)* In vitro DMSO 83 mg/mL (198.38 mM)
Ethanol 20 mg/mL (47.8 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description GNF-5 is a selective and allosteric Bcr-Abl inhibitor with IC50 of 220 nM.
Targets
Bcr-Abl [1]
220 nM
In vitro GNF-5, when used in combination with imatinib or nilotinib, suppresses the emergence of resistance mutations in vitro, and displays additive inhibitory activity in biochemical and cellular assays against Bcr-Abl T315I mutant. [1] GNF-5 shows potent antiproliferative activity with EC50 of 430 nM and 580 nM against wt-Bcr-Abl and E255K mutant Bcr-Abl transformed cells, respectively. [2]
In vivo GNF-5 (100 mg/kg ) displays efficacy on wild-type and T315I Bcr-Abl dependent proliferation in xenograft and bone marrow transplantation models. Moreover, a combination of GNF-5 (75 mg/kg) with nilotinib (50 mg/kg) results in improved overall survival in a T315I Bcr-Abl BMT model. [1]

Protocol (from reference)

Kinase Assay:[1]
  • Kinetic characterization of Abl inhibition

    The ATP/NADH-coupled assay system in a 96-well format is used to determine the initial velocity of Abl tyrosine kinase catalyzed peptide phosphorylation. The reaction mixture contained 20 mM Tris-HCl, (pH 8.0), 50 mM NaCl, 10 mM MgCl2, 2 mM PEP [2-(Phosphonooxy)- 2-propenoic acid) and 20 μg Abl peptide substrate (EAIYAAPFAKKK), fixed or varied (to determine inhibitor kinetic parameters) concentration of inhibitor applied, 1/50 of the final reaction mixture volume of PK/LDH enzyme (pyruvate kinase/lactic dehydrogenase enzymes from rabbit muscle), 160 μM NADH, 0.16 μM Abl, and ATP added last to start the reaction. Absorbance data are collected every 20s at 340 nm using a SpectraMax M5 Microplate Reader.

Cell Assay:[2]
  • Cell lines

    Ba/F3.p210 cells

  • Concentrations

    ~10 μM

  • Incubation Time

    48 hours

  • Method

    Ba/F3.p210 cells are obtained by transfecting the IL-3-dependent murine hematopoietic Ba/F3 cell line with a pEYK vector containing p210BCR-ABL and Bcr-Abl mutations. All cell lines are cultured with 5% CO2 at 37 °C in RPMI 1640 with 10% fetal bovine serum (FBS) and supplemented with 1% l-glutamine. Parental Ba/F3 cells are similarly cultured with 10% WEHI-conditioned medium as a source of IL-3. Transfected cell lines are cultured in media supplemented with 25 μg/mL zeocin. The 48 h cell proliferation studies are obtained using the CellTiter-Glo assay.
Animal Study:[1]
  • Animal Models

    Ba/F3.p210 xenograft mouse model

  • Dosages

    ~100 mg/kg bid

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Leukemia, 2017, 31(5):1096-1107]

Data from [Data independently produced by , , Oncotarget, 2017, 8(24):38717-38730]

Selleck's GNF-5 has been cited by 15 publications

Structural mechanism of a drug-binding process involving a large conformational change of the protein target [ Nat Commun, 2023, 14(1):1885] PubMed: 37019905
Src stimulates Abl-dependent phosphorylation of the guanine exchange factor Net1A to promote its cytosolic localization and cell motility [ J Biol Chem, 2023, S0021-9258(23)01915-4] PubMed: 37271338
Abl kinases can function as suppressors of tumor progression and metastasis [ Front Oncol, 2023, 13:1241056] PubMed: 37746268
Abl kinases can function as suppressors of tumor progression and metastasis [ Front Oncol, 2023, 10.3389/fonc.2023.1241056] PubMed: 37746268
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] PubMed: 34997030
Imatinib can act as an Allosteric Activator of Abl Kinase [ J Mol Biol, 2021, 434(2):167349] PubMed: 34774565
ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice [ Gastroenterology, 2020, S0016-5085(20)30334-6] PubMed: 32171747
Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling [ Nat Commun, 2020, 11(1):5463] PubMed: 33122628
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004] PubMed: 31740922
Abl and Arg mediate cysteine cathepsin secretion to facilitate melanoma invasion and metastasis [ Sci Signal, 2018, 11(518)eaao0422] PubMed: 29463776

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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