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Purity: =99.73%
Poziotinib (formerly known as HM781-36B, NOV120101, HM781 36B) is a novel, potent, orally bioavailable, quinazoline-based, irreversible/co-valent pan-inhibitor of HER (human epidermal growth factor receptor 2) with potential antitumor activity. It has an IC50 of 3.2 nM, 5.3 nM, and 23.5 nM for HER1, HER2, and HER4 inhibition, respectively. HER2 and HER4 are also irreversibly inhibited by HM781-36B, which prevents the growth of tumor cells that overexpress these receptors. This includes EGFR (HER1 or ErbB1), including EGFR mutants. A multitude of cancer cell types frequently exhibit increased expression of EGFRs, or cell surface receptor tyrosine kinases, which are essential for cellular survival and proliferation.
| Targets |
HER1 (IC50 = 3.2 nM); HER2 (IC50 = 5.3 nM); HER4 (IC50 = 23.5 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
In Sf9 insect cells, the enzymes of EGFR, HER2, and HER4 are expressed as recombinant proteins in order to calculate the IC50 values of HM781-36B for kinase inhibition. Next, utilizing a tyrosine kinase assay kit, enzyme selectivity screening is carried out. In summary, the reactions take place in 96-well polystyrene round-bottomed plates that hold kinase buffer, which is made up of 250 μM Na3VO4, 25 mM MgCl2, 10 mM MnCl2, and 100 mM HEPES (pH 7.4). The addition of 10 ng/mL poly(Glu, Tyr), 100 μM ATP, and 100 ng/assay enzyme starts the reactions. The reactions are stopped by adding 6 mM EDTA solution, anti-phosphotyrosine antibody, PTK Green Tracer, and FP dilution buffer mixtures after a one-hour room temperature incubation period. After 30 minutes at room temperature, the fluorescence polarization values are determined using a Victor3 microplate reader. Y = bottom + (top–bottom)/(1 + 10(X-logIC50)) was the formula used to finally compute the IC50 values.
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| Cell Assay |
Using an MTT reduction assay, viable cell growth is observed. All cell lines are, in short, seeded in 96-well culture plates at a density of 3 × 103 per well, and then incubated for 24 hours at 37 °C. Next, different concentrations of HM781-36B—0.001, 0.01, 0.1, or 10 μM—are applied to the cells. A quarter of an hour is spent incubating the samples to lessen the dye after 50 micrograms of MTT is added to each well three days later. The absorbance of the converted dye in the living cells is then measured at a wavelength of 540 nm after the samples are treated with DMSO. For every analysis, six duplicate wells are utilized, and a minimum of three separate trials are carried out. The mean is represented by the data points, and the SE is shown by the bars.
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| Animal Protocol |
BALB/c athymic nude mice bearing N87 xenografts
0.5 mg/kg daily p.o. |
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| References |
| Molecular Formula |
C23H21CL2FN4O3
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| Molecular Weight |
491.34
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| Exact Mass |
490.10
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| Elemental Analysis |
C, 56.22; H, 4.31; Cl, 14.43; F, 3.87; N, 11.40; O, 9.77
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| CAS # |
1092364-38-9
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| Related CAS # |
1092364-38-9;1429757-68-5 (HCl);1352121-00-6 (x HCl);1352121-01-7 (phosphate);1352121-02-8 (sulfate);1352121-09-5 (besylate);1352121-06-2 (citrate);1352121-05-1;1352121-04-0 (malate);1352121-07-3 (fumarate)
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| Appearance |
Pale yellow solid powder
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| SMILES |
COC1=C(C=C2C(=C1)N=CN=C2NC3=C(C(=C(C=C3)Cl)Cl)F)OC4CCN(CC4)C(=O)C=C
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| InChi Key |
LPFWVDIFUFFKJU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21Cl2FN4O3/c1-3-20(31)30-8-6-13(7-9-30)33-19-10-14-17(11-18(19)32-2)27-12-28-23(14)29-16-5-4-15(24)21(25)22(16)26/h3-5,10-13H,1,6-9H2,2H3,(H,27,28,29)
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| Chemical Name |
1-[4-[4-(3,4-dichloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]prop-2-en-1-one
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| Synonyms |
HM781-36B; HM78136B; HM-78136B; NOV120101; Poziotinib; NOV-120101; NOV 120101; HM 78136B
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
2% DMSO+40% PEG 300+2% Tween 80+ddH2O: 5mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0353 mL | 10.1763 mL | 20.3525 mL | |
| 5 mM | 0.4071 mL | 2.0353 mL | 4.0705 mL | |
| 10 mM | 0.2035 mL | 1.0176 mL | 2.0353 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03066206 | Active Recruiting |
Drug: Poziotinib | EGFR Exon 20 Mutation ERBB2 Gene Mutation |
M.D. Anderson Cancer Center | February 20, 2023 | Phase 2 |
| NCT03318939 | Active Recruiting |
Drug: Poziotinib | NSCLC | Spectrum Pharmaceuticals, Inc | October 13, 2017 | Phase 2 |
| NCT02659514 | Completed | Drug: Poziotinib | Breast Cancer | Spectrum Pharmaceuticals, Inc | February 22, 2016 | Phase 2 |
| NCT03292250 | Completed | Drug: Poziotinib Drug: Nintedanib |
HNSCC Head and Neck Neoplasms |
Seoul National University Hospital |
September 10, 2017 | Phase 2 |
| NCT01455571 | Completed | Drug: HM781-36B | Advanced Solid Tumor | Hanmi Pharmaceutical Company Limited |
November 2009 | Phase 1 |
Basal level expression of the HER family and BMX, and fluorescencein situhybridization (FISH) analysis in CRC cell lines. |
The growth inhibitory effect of HM781-36B on a panel of human colorectal carcinoma cell lines.
The synergistic effect of colorectal cancer cells treated with HM781-36B in combination with chemotherapeutic drugs (oxaliplatin [L-OHP], 5-fluorouracil [5-FU], and SN-38). |
Analysis of the cell cycle and apoptosis in colorectal carcinoma cell lines after HM781-36B treatment.
Protein expression of the HER family and downstream signaling molecules in colorectal cancer cells following treatment with HM781-36B. |
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