Poziotinib (HM781-36B)

Catalog No.S7358 Synonyms: NOV120101

For research use only.

Poziotinib (HM781-36B, NOV120101) 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.

Poziotinib (HM781-36B) Chemical Structure

CAS No. 1092364-38-9

Selleck's Poziotinib (HM781-36B) has been cited by 20 publications

Purity & Quality Control

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Biological Activity

Description Poziotinib (HM781-36B, NOV120101) 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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A431 MljPRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M1;mZlczKGi{cx?= MXjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF2M{GgZ4VtdHNiZYjwdoV{e2mwZzD3bYxlKHS7cHWgSWdHWiCrbnP1ZoF1\WRiZn;yJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUCgQUAxNjByMEmg{txONg>? MofkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5NUS0O|EoRjJ6N{W0OFcyRC:jPh?=
SKBR3 NITXfY5CdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MVS3NkBpenN? M3jNeWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1vCVlMh[2WubIOg[ZhxemW|c3nu[{B4cWymIIT5dIUhUEWUMjDpcoN2[mG2ZXSg[o9zKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSByLkCwNUDPxE1w NIXuU|E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe1OFQ4OSd-Mki3OVQ1PzF:L3G+
Ba/F3 NWfieI1PTnWwY4Tpc44h[XO|YYm= MVzJcohq[mm2aX;uJI9nKGi3bXHuJGVITlJiVEe5NG0wVDh3OGKgcZV1[W62IHX4dJJme3OnZDDpckBud3W|ZTDCZU9HOyClZXzsd{whUUN3MDC9JFAvODB{MjFOwG0v NHfZboI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe1OFQ4OSd-Mki3OVQ1PzF:L3G+
insect cells M2fQN2Z2dmO2aX;uJIF{e2G7 MoriTY5pcWKrdHnvckBw\iCJU2SteIFo\2WmIHj1cYFvKEWJRmKgZ4F1[Wy7dHnjJIRwdWGrbjDlfJBz\XO|ZXSgbY4hcW6|ZXP0JINmdGy|LDDJR|UxKD1iMD6wNFMzKM7:TT6= MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDd3NES3NUc,Ojh5NUS0O|E9N2F-
Ba/F3 MkD0SpVv[3Srb36gZZN{[Xl? NVXXRoo2UW6qaXLpeIlwdiCxZjDoeY1idiCHR1\SJHQ4QTCPIH31eIFvfCCneIDy[ZN{\WRiaX6gcY92e2ViQnGvSlMh[2WubIOsJGlEPTBiPTCwMlAxPDJizszNMi=> NFrRWpU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEe1OFQ4OSd-Mki3OVQ1PzF:L3G+
insect cells MmnnSpVv[3Srb36gZZN{[Xl? NU\vSmNtUW6qaXLpeIlwdiCxZjDHV3QufGGpZ3XkJIh2dWGwIFjFVlIh[2G2YXz5eIlkKGSxbXHpckBmgHC{ZYPz[YQhcW5iaX7z[YN1KGOnbHzzMEBKSzVyIE2gNE4xODV|IN88UU4> M{P6ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6N{W0OFcyLz5{OEe1OFQ4OTxxYU6=
NCI-H1975 MUnBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MWC3NkBpenN? M4LvU2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWgyQTd3IHPlcIx{KGW6cILld5NqdmdiRVfGVkBVPzlyTT;MPFU5WiCvdYThcpQhcW6ldXLheIVlKG[xcjC3NkBpenNiYomgUXRUKGG|c3H5MEBKSzVyIE2gNE4xODV5IN88UU4> NVLnR3RtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki3OVQ1PzFpPkK4O|U1PDdzPD;hQi=>
HS27 NV22TnExSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MXO3NkBpenN? Mnu5RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKU{K3JINmdGy|IHX4dJJme3Orbnege4lt\CC2eYDlJGhGWjJiaX7jeYJifGWmIH\vdkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCJSUWwJF0hOy56MzFOwG0v MljTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh5NUS0O|EoRjJ6N{W0OFcyRC:jPh?=
SKBR3 MWDBcpRq[2GwY3XyJIF{e2G7 M4PyVlczKGi{cx?= M2S0TmFvfGmlYX7j[ZIh[WO2aY\peJkh[WejaX7zeEBGemJvQkKgc5ZmemW6cILld5NqdmdiaIXtZY4hW0uEUkOgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCLREWwJF0hOC5yMECzJO69VS5? MoPMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|U1PTF3ND:nQmNpTU2ETEyvZV4>
A431 NHLXbZRCdnSrY3HuZ4VzKGG|c3H5 MkPTO|IhcHK| MmWyRY51cWOjbnPldkBi[3Srdnn0fUBi\2GrboP0JGVITlJib4\ldoV5eHKnc4PpcochcHWvYX6gRVQ{OSClZXzsd{Bie3Onc4Pl[EBieyClZXzsJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEeyJIhzeyCkeTDTVmIh[XO|YYmsJGlFPTBiPTCwMlAxODRizszNMi=> M{HxXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFM2PDVzNUSvK|5EcEWPQly8M4E,
Sf21 M3qycGZ2dmO2aX;uJIF{e2G7 NFTvUW0yOCCvaX7z NHjHdmZKdmirYnn0bY9vKG:oIF6teIVzdWmwYXygS3NVNXSjZ3fl[EBpfW2jbjDFS2ZTKCh4OU[geI8h\W6mIILld4llfWW|KTDlfJBz\XO|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRiU3[yNUBk\WyuczD1d4lv\yCyb3z5JEhIdHVuVInyLVQ7OSCjczDzeYJ{fHKjdHWgdJJmcW6ldXLheIVlKG[xcjCxNEBucW6|IH\vcIxwf2WmIHL5JJN2[nO2cnH0[UBi\GSrdHnvckBu\WG|dYLl[EBi\nSncjCxJIhzKGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25uIFnDOVAhRSByLkCwNVMh|ryPLh?= MkHmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|U1PTF3ND:nQmNpTU2ETEyvZV4>
NCI-H1975 MkX2RY51cWOjbnPldkBie3OjeR?= NXfDOWZPPDhiaILz M1S5c2FvfGmlYX7j[ZIh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDF7N{WgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkA1QCCqcoOgZpkh[2WubITpeIVzKG:wZTDzbI91KHOxbIX0bY9vKGG|c3H5MEBKSzVyIE2gNE4xODJ5IN88UU4> MnrGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMN|U1PTF3ND:nQmNpTU2ETEyvZV4>
Sf21 MnL3SpVv[3Srb36gZZN{[Xl? M1fYblExKG2rboO= MUHJcohq[mm2aX;uJI9nKE5vdHXycYlv[WxiR2PUMZRi\2enZDDy[YNwdWKrbnHueEBpfW2jbjDFS2ZTKFR5OUDNJI12fGGwdDDlfJBz\XO|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRiU3[yNUBk\WyuczD1d4lv\yCyb3z5JEhIdHVuVInyLVQ7OSCjczDzeYJ{fHKjdHWgdJJmcW6ldXLheIVlKG[xcjCxNEBucW6|IH\vcIxwf2WmIHL5JJN2[nO2cnH0[UBi\GSrdHnvckBu\WG|dYLl[EBi\nSncjCxJIhzKGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZQtKEmFNUCgQUAxNjByNESg{txONg>? MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyzOVQ2OTV2Lze+R4hGVUKOPD;hQi=>
Assay
Methods Test Index PMID
Western blot Cleaved caspase-3 / Cleaved caspase-9 / PARP / Bcl-2 ; pEGFR / EGFR / pHER2 / HER2 / BMX / pERK / ERK / pAKT / AKT 25761479
Growth inhibition assay Cell viability 25761479
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 Research:[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 Research:[1]
  • Animal Models: BALB/c athymic nude mice bearing N87 xenografts
  • Dosages: 0.5 mg/kg daily
  • Administration: p.o.

Solubility (25°C)

In vitro

DMSO 98 mg/mL
(199.45 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
2% DMSO+40% PEG 300+2% Tween 80+ddH2O
For best results, use promptly after mixing.

5mg/mL

Chemical Information

Molecular Weight 491.34
Formula

C23H21Cl2FN4O3

CAS No. 1092364-38-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=C(C=C2C(=C1)N=CN=C2NC3=C(C(=C(C=C3)Cl)Cl)F)OC4CCN(CC4)C(=O)C=C

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04436562 Completed Drug: [14C]-Poziotinib Healthy Spectrum Pharmaceuticals Inc May 29 2020 Phase 1
NCT03804515 Terminated Drug: 14C-labeled poziotinib Solid Tumor Spectrum Pharmaceuticals Inc June 25 2019 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

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