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Poziotinib (HM781-36B)

Name: Poziotinib (HM781-36B)
Brand: Selleck Chemicals
SKU: S7358
Rating: 5 (20 reviews)

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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EGFR Signaling Pathway Map

Biological Activity

Description

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=>

Click to View More Cell Line Experimental Data

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.

References

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. Click to purchase: PEG300 Tween 80	5mg/mL

Chemical Information

Molecular Weight	491.34
Formula	C₂₃H₂₁Cl₂FN₄O₃
CAS No.	1092364-38-9
Storage	3 years	-20°C	powder
Storage	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

Download Poziotinib (HM781-36B) SDF

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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)

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