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

Jump to

Quality Control

Batch: Purity: 99.37%

99.37

Related Targets	VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2 c-Kit
Other EGFR Products	Lazertinib (YH25448) Sunvozertinib Icotinib Hydrochloride AG-490 AG-1478 Canertinib (CI-1033) Rociletinib (CO-1686) WZ4002 Genistein PD153035

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
A431	Antiproliferative assay	72 hrs	Antiproliferative activity against human A431 cells expressing wild type EGFR incubated for 72 hrs by MTS assay, IC50 = 0.0009 μM.	28754471
SKBR3	Antiproliferative assay	72 hrs	Antiproliferative activity against human SKBR3 cells expressing wild type HER2 incubated for 72 hrs by MTS assay, IC50 = 0.001 μM.	28754471
Ba/F3	Function assay		Inhibition of human EGFR T790M/L858R mutant expressed in mouse Ba/F3 cells, IC50 = 0.0022 μM.	28754471
insect cells	Function assay		Inhibition of GST-tagged human EGFR catalytic domain expressed in insect cells, IC50 = 0.0032 μM.	28754471
Ba/F3	Function assay		Inhibition of human EGFR T790M mutant expressed in mouse Ba/F3 cells, IC50 = 0.0042 μM.	28754471
insect cells	Function assay		Inhibition of GST-tagged human HER2 catalytic domain expressed in insect cells, IC50 = 0.0053 μM.	28754471
NCI-H1975	Antiproliferative assay	72 hrs	Antiproliferative activity against human NCI-H1975 cells expressing EGFR T790M/L858R mutant incubated for 72 hrs by MTS assay, IC50 = 0.0057 μM.	28754471
HS27	Antiproliferative assay	72 hrs	Antiproliferative activity against human HS27 cells expressing wild type HER2 incubated for 72 hrs by MTS assay, GI50 = 3.83 μM.	28754471
SKBR3	Anticancer assay	72 hrs	Anticancer activity against Erb-B2 overexpressing human SKBR3 cells assessed as cell growth inhibition after 72 hrs by SRB assay, ID50 = 0.0003 μM.	ChEMBL
A431	Anticancer assay	72 hrs	Anticancer activity against EGFR overexpressing human A431 cells assessed as cell growth inhibition after 72 hrs by SRB assay, ID50 = 0.0004 μM.	ChEMBL
Sf21	Function assay	10 mins	Inhibition of N-terminal GST-tagged human EGFR (696 to end residues) expressed in baculovirus infected Sf21 cells using poly (Glu,Tyr)4:1 as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by fluorescence polarization, IC50 = 0.0013 μM.	ChEMBL
NCI-H1975	Anticancer assay	48 hrs	Anticancer activity against human NCI-H1975 cells assessed as cell growth inhibition after 48 hrs by celltiter one shot solution assay, IC50 = 0.0027 μM.	ChEMBL
Sf21	Function assay	10 mins	Inhibition of N-terminal GST-tagged recombinant human EGFR T790M mutant expressed in baculovirus infected Sf21 cells using poly (Glu,Tyr)4:1 as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by fluorescence polarizat, IC50 = 0.0044 μM.	ChEMBL
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 98 mg/mL (199.45 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	491.34	Formula	C₂₃H₂₁Cl₂FN₄O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1092364-38-9	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	HM781-36B, NOV120101			Smiles	COC1=C(C=C2C(=C1)N=CN=C2NC3=C(C(=C(C=C3)Cl)Cl)F)OC4CCN(CC4)C(=O)C=C

Mechanism of Action

Targets/IC₅₀/Ki	HER1 (Cell-free assay) 3.2 nM HER2 (Cell-free assay) 5.3 nM HER4 (Cell-free assay) 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. This compound also induces apoptosis and G1 cell cycle arrest by activating the mitochondrial pathway in HER2 amplified gastric cancer cells. Furthermore, it also exerts synergistic effects with chemotherapeutic agents in both HER2 amplified and HER2 non-amplified gastric cancer cells.
Kinase Assay	Enzyme activity assay
Kinase Assay	To determine the IC50 values of Poziotinib 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)).
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 this compound and 5-FU causes more effective tumor inhibition. In addition, this compound 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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/21306821/ [2] https://pubmed.ncbi.nlm.nih.gov/21732342/

Applications

Methods	Biomarkers	Images	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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04436562	Completed	Healthy	Spectrum Pharmaceuticals Inc	May 29 2020	Phase 1
NCT03804515	Terminated	Solid Tumor	Spectrum Pharmaceuticals Inc	June 25 2019	Phase 1

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Poziotinib (HM781-36B) EGFR inhibitor

Chemical Structure

Molecular Weight: 491.34