Poziotinib

Catalog No.S7358 Batch:S735805

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Technical Data

Formula

C23H21Cl2FN4O3
Molecular Weight 491.34 CAS No. 1092364-38-9
Solubility (25°C)* In vitro DMSO 98 mg/mL (199.45 mM)
Water Insoluble
Ethanol 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.)

Preparing Stock Solutions

Biological Activity

Description Poziotinib is an irreversible pan-HER inhibitor with IC50 of 3.2 nM, 5.3 nM and 23.5 nM for HER1, HER2, and HER4, respectively. Poziotinib also induces apoptosis and G1 cell cycle arrest. Phase 2.
Targets
HER1 [1]
(Cell-free assay)		 HER2 [1]
(Cell-free assay)		 HER4 [1]
(Cell-free assay)
3.2 nM 5.3 nM 23.5 nM
In vitro Poziotinib specifically inhibits the cell growth in HER2 amplified gastric cancer cells, and inhibits the phosphorylation of EGFR and key components of downstream signaling cascades such as STAT3, AKT and ERK. Poziotinib also induces apoptosis and G1 cell cycle arrest by activating the mitochondrial pathway in HER2 amplified gastric cancer cells. Furthermore, Poziotinib also exerts synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells. [1]
In vivo In nude mice bearing N87 human gastric cancer xenografts, Poziotinib (0.5 mg/kg p.o.) alone significantly inhibits the growth of tumors, and coadministraion of Poziotinib and 5-FU causes more effective tumor inhibition. [1] In addition, HM781-36B shows excellent antitumor activity in a variety of EGFR- and HER-2-dependent tumor xenograft models, including erlotinib-sensitive HCC827 NSCLC cells, erlotinib-resistant NCI-H1975 NSCLC cells, HER-2 overexpressing Calu-3 NSCLC cells, NCI-N87 gastric cancer cells, SK-Ov3 ovarian cancer cells and EGFR-overexpressing A431 epidermoid carcinoma cancer cells. [2]

Protocol (from reference)

Kinase Assay:[1]
  • Enzyme activity assay

    To determine the IC50 values of HM781-36B for kinase inhibition, enzymes of EGFR, HER2, and HER4 are expressed as recombinant proteins in Sf9 insect cells. Enzyme selectivity screening is then performed using a tyrosine kinase assay kit. Briefly, the reactions are performed in 96 well polystyrene round-bottomed plates containing kinase buffer composed of 100 mM HEPES (pH 7.4), 25 mM MgCl2, 10 mM MnCl2 and 250 μM Na3VO4. The reactions are initiated by the addition of 100 ng/assay enzyme, 100 μM ATP, and 10 ng/mL poly(Glu, Tyr). After 1 h of incubation at room temperature, the reactions are terminated by adding 6 mM EDTA solution and then anti-phosphotyrosine antibody, PTK Green Tracer, and FP dilution buffer mixtures. The fluorescence polarization values are then measured after 30 min at room temperature using a Victor3 microplate reader. Finally, the IC50 values were calculated using the following equation: Y = bottom + (top–bottom)/(1 + 10(X-logIC50)).
Cell Assay:[1]
  • Cell lines

    Gastric cancer cell lines (SNU-1, 5, 16, 216, 484, 601, 620, 638, 668, 719, N87 and AGS)

  • Concentrations

    ~10 μM

  • Incubation Time

    72 hours

  • Method

    Viable cell growth is determined by an MTT reduction assay. Briefly, all cell lines are seeded at a density of 3 × 103 per well in 96-well culture plates and then incubated at 37 °C for 24 h. The cells are then treated with 0.001, 0.01, 0.1, or 10 μM of HM781-36B. Three days later, 50 μg of MTT are added to each well and the samples are then incubated for 4 h to reduce the dye. Next, the samples are treated with DMSO, after which the absorbance of the converted dye in the living cells is measured at a wavelength of 540 nm. Six replicate wells are used for each analysis, and at least three independent experiments are conducted. Data points shown represent the mean while bars represent the SE.
Animal Study:[1]
  • Animal Models

    BALB/c athymic nude mice bearing N87 xenografts

  • Dosages

    0.5 mg/kg daily

  • Administration

    p.o.

Selleck's Poziotinib has been cited by 36 publications

Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists [ iScience, 2024, 27(2):108839] PubMed: 38303712
Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis [ Int J Mol Sci, 2024, 25(7)3992] PubMed: 38612799
Protocol for identifying properties of ERBB receptor antagonists using the barcoded ERBBprofiler assay [ STAR Protoc, 2024, 5(2):102987] PubMed: 38635397
Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis [ bioRxiv, 2024, 2024.02.19.581073] PubMed: 38529509
Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion [ J Thorac Oncol, 2023, S1556-0864(23)00797-9] PubMed: 37666482
HER4 and EGFR activate cell signaling in NRG1 fusion-driven cancers: implications for HER2/HER3-specific vs. pan-HER targeting strategies [ J Thorac Oncol, 2023, S1556-0864(23)00802-X] PubMed: 37678511
SMYD5 is a novel epigenetic gatekeeper of the mild hypothermia response [ bioRxiv, 2023, 2023.05.11.540170] PubMed: 37333301
Clinical Relevance of Patient-Derived Organoid of Surgically Resected Lung Cancer as an In Vitro Model for Biomarker and Drug Testing [ JTO Clin Res Rep, 2023, 4(9):100554] PubMed: 37681218
SMYD5 is a novel epigenetic gatekeeper of the mild hypothermia response [ bioRxiv, 2023, 2023.05.11.540170] PubMed: 37333301
Clinical Relevance of Patient-Derived Organoid of Surgically Resected Lung Cancer as an In Vitro Model for Biomarker and Drug Testing [ JTO Clin Res Rep, 2023, 4(9):100554] PubMed: 37681218

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