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MedKoo Cat#: 205846 | Name: Poziotinib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Poziotinib , also known as HM781-36B and NOV120101, is an orally bioavailable, quinazoline-based pan epidermal growth factor receptor (EGFR or HER) inhibitor with potential antineoplastic activity. HM781-36B irreversibly inhibits EGFR (HER1 or ErbB1), including EGFR mutants, HER2, and HER4, thereby inhibiting the proliferation of tumor cells that overexpress these receptors. EGFRs, cell surface receptor tyrosine kinases, are often upregulated in a variety of cancer cell types and play key roles in cellular proliferation and survival.

Chemical Structure

Poziotinib
Poziotinib
CAS#1092364-38-9 (free base)

Theoretical Analysis

MedKoo Cat#: 205846

Name: Poziotinib

CAS#: 1092364-38-9 (free base)

Chemical Formula: C23H21Cl2FN4O3

Exact Mass: 490.0975

Molecular Weight: 491.34

Elemental Analysis: C, 56.22; H, 4.31; Cl, 14.43; F, 3.87; N, 11.40; O, 9.77

Price and Availability

Size Price Availability Quantity
10mg USD 110.00 Ready to ship
25mg USD 220.00 Ready to ship
50mg USD 400.00 Ready to ship
100mg USD 700.00 Ready to ship
200mg USD 1,050.00 Ready to Ship
500mg USD 2,250.00 Ready to ship
1g USD 2,950.00 Ready to ship
2g USD 5,250.00 Ready to Ship
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Related CAS #
1092364-38-9 (free base) 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 (maleate) 1352121-04-0 (malate) 1352121-07-3 (fumarate)
Synonym
HM781-36B; HM78136B; HM-78136B; HM 78136B; NOV120101; NOV-120101; NOV 120101; Poziotinib
IUPAC/Chemical Name
1-(4-((4-((3,4-dichloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)prop-2-en-1-one
InChi Key
LPFWVDIFUFFKJU-UHFFFAOYSA-N
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)
SMILES Code
C=CC(N1CCC(OC2=CC3=C(NC4=CC=C(Cl)C(Cl)=C4F)N=CN=C3C=C2OC)CC1)=O
Appearance
Pale yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
Poziotinib (HM781-36B) is a pan-HER inhibitor, which effectively inhibits EGFRwt, HER-2 and HER-4 with IC50s of 3.2, 5.3 and 23.5 nM, respectively.
In vitro activity:
Poziotinib, a pan-human epidermal growth factor receptor (HER) inhibitor, decreased sphere formation, viability, and proliferation, and induced G1 cell cycle arrest and apoptosis in ovarian CSCs (cancer stem cells). In addition, poziotinib suppressed stemness and disrupted downstream signaling of Wnt/β-catenin, Notch, and Hedgehog pathways, which contribute to many characteristics of CSCs. Interestingly, HER4 was overexpressed in ovarian CSCs and Poziotinib reduced the phosphorylation of STAT5, AKT, and ERK, which are regulated by HER4. Reference: Biochem Biophys Res Commun. 2020 May 21;526(1):158-164. https://www.sciencedirect.com/science/article/abs/pii/S0006291X20305271?via%3Dihub
In vivo activity:
The in vivo activity of HM781-36B was assessed in xenograft mice models with various EGFR-dependent cancer cell lines. Daily oral treatments of HM781-36B at 0.3 mg/kg/day or 1 mg/kg/day for 10 days resulted in a dramatic reduction of tumor size with an 83% maximum inhibition rate (mIR, IR = [1 − (relative tumor growth in treated group/relative tumor growth in control group)] × 100) at 0.3 mg/kg/day without body-weight loss. The effect of HM781-36B on HCC827 tumor endothelium was evaluated by immunohistochemistry and a significant reduction in the expression level of pEGFR, pAKT and pERK was observed upon treatment with HM781-36B (0.3 mg/kg/day) for 10 days (Fig. 3b). Reference: Int J Cancer. 2012 May 15;130(10):2445-54. https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.26276
Solvent mg/mL mM
Solubility
DMSO 20.0 40.70
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 491.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Cha MY, Lee KO, Kim M, Song JY, Lee KH, Park J, Chae YJ, Kim YH, Suh KH, Lee GS, Park SB, Kim MS. Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models. Int J Cancer. 2012 May 15;130(10):2445-54. doi: 10.1002/ijc.26276. Epub 2011 Aug 24. PMID: 21732342. 2. Lee H, Kim JW, Choi DK, Yu JH, Kim JH, Lee DS, Min SH. Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway. Biochem Biophys Res Commun. 2020 May 21;526(1):158-164. doi: 10.1016/j.bbrc.2020.03.046. Epub 2020 Mar 20. PMID: 32201081.
In vitro protocol:
1. Cha MY, Lee KO, Kim M, Song JY, Lee KH, Park J, Chae YJ, Kim YH, Suh KH, Lee GS, Park SB, Kim MS. Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models. Int J Cancer. 2012 May 15;130(10):2445-54. doi: 10.1002/ijc.26276. Epub 2011 Aug 24. PMID: 21732342. 2. Lee H, Kim JW, Choi DK, Yu JH, Kim JH, Lee DS, Min SH. Poziotinib suppresses ovarian cancer stem cell growth via inhibition of HER4-mediated STAT5 pathway. Biochem Biophys Res Commun. 2020 May 21;526(1):158-164. doi: 10.1016/j.bbrc.2020.03.046. Epub 2020 Mar 20. PMID: 32201081.
In vivo protocol:
1. Cha MY, Lee KO, Kim M, Song JY, Lee KH, Park J, Chae YJ, Kim YH, Suh KH, Lee GS, Park SB, Kim MS. Antitumor activity of HM781-36B, a highly effective pan-HER inhibitor in erlotinib-resistant NSCLC and other EGFR-dependent cancer models. Int J Cancer. 2012 May 15;130(10):2445-54. doi: 10.1002/ijc.26276. Epub 2011 Aug 24. PMID: 21732342.
1: Park S, Park S, Kim TM, Kim S, Koh J, Lim J, Yi K, Yi B, Ju YS, Kim M, Keam B, Kim JS, Jeon YK, Kim DW, Kim YT, Heo DS. Resistance mechanisms of EGFR tyrosine kinase inhibitors, in EGFR exon 20 insertion-mutant lung cancer. Eur J Cancer. 2024 Jul 4;208:114206. doi: 10.1016/j.ejca.2024.114206. Epub ahead of print. PMID: 38981315. 2: Seo D, Lim JH. Targeted Therapies for EGFR Exon 20 Insertion Mutation in Non- Small-Cell Lung Cancer. Int J Mol Sci. 2024 May 29;25(11):5917. doi: 10.3390/ijms25115917. PMID: 38892105; PMCID: PMC11172945. 3: Park J, Lee B, Song JY, Sung M, Kwon MJ, Kim CR, Lee S, Shin YK, Choi YL. Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine. Pathology. 2024 Aug;56(5):653-661. doi: 10.1016/j.pathol.2024.02.012. Epub 2024 May 6. PMID: 38811262. 4: Yang G, Liu R, Tang X. Dacomitinib exhibits promising activity against the rare HER2 exon 20 insertion M774delinsWLV in lung cancer: A case report and literature review. Heliyon. 2024 Apr 26;10(9):e30312. doi: 10.1016/j.heliyon.2024.e30312. PMID: 38707278; PMCID: PMC11068806. 5: Ippolitov D, Lin YH, Spence J, Glogowska A, Thanasupawat T, Beiko J, Del Bigio MR, Xu X, Wang A, Calvo R, Kapoor A, Marugan JJ, Henderson MJ, Klonisch T, Hombach-Klonisch S. Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis. bioRxiv [Preprint]. 2024 Feb 22:2024.02.19.581073. doi: 10.1101/2024.02.19.581073. PMID: 38529509; PMCID: PMC10962705. 6: Nasrazadani A, Marti JLG, Lathrop K, Restrepo A, Leu SY, Bhat G, Brufsky A. Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens. Breast Cancer Res Treat. 2024 May;205(1):29-37. doi: 10.1007/s10549-023-07236-z. Epub 2024 Jan 23. PMID: 38261228. 7: Kobayashi IS, Shaffer W, Viray H, Rangachari D, VanderLaan PA, Kobayashi SS, Costa DB. The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors. JTO Clin Res Rep. 2023 Nov 27;5(1):100614. doi: 10.1016/j.jtocrr.2023.100614. PMID: 38229766; PMCID: PMC10788275. 8: Sun X, Wu Y, Xu F, Liu C. Screening of potent RIPK3 inhibitors to attenuate necroptosis and inflammation in mouse traumatic brain injury models. Exp Neurol. 2024 Feb;372:114633. doi: 10.1016/j.expneurol.2023.114633. Epub 2023 Dec 5. PMID: 38061556. 9: Bellur S, Khosla AA, Ozair A, Kotecha R, McDermott MW, Ahluwalia MS. Management of Brain Metastases: A Review of Novel Therapies. Semin Neurol. 2023 Dec;43(6):845-858. doi: 10.1055/s-0043-1776782. Epub 2023 Nov 27. PMID: 38011864. 10: Alamery S, AlAjmi A, Wani TA, Zargar S. In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes. Medicina (Kaunas). 2023 Oct 30;59(11):1923. doi: 10.3390/medicina59111923. PMID: 38003971; PMCID: PMC10673591. 11: Kalra R, Lim B, Ellis MJ, Kavuri SM. The uncharted role of HER2 mutant alleles in breast cancer. Oncotarget. 2023 Oct 31;14:904-907. doi: 10.18632/oncotarget.28489. PMID: 37921670; PMCID: PMC10624202. 12: Keam B, Hong MH, Shin SH, Heo SG, Kim JE, Ahn HK, Lee YG, Park KU, Yun T, Lee KW, Kim SB, Lee SC, Kim MK, Cho SH, Oh SY, Park SG, Hwang S, Nam BH, Kim S, Kim HR, Yun HJ; KCSG TRIUMPH Investigators. Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial. J Clin Oncol. 2024 Feb 10;42(5):507-517. doi: 10.1200/JCO.22.02786. Epub 2023 Sep 12. PMID: 37699162. 13: Sentana-Lledo D, Academia E, Viray H, Rangachari D, Kobayashi SS, VanderLaan PA, Costa DB. EGFR exon 20 insertion mutations and ERBB2 mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates. Transl Lung Cancer Res. 2023 Jul 31;12(7):1590-1610. doi: 10.21037/tlcr-23-98. Epub 2023 Jul 5. PMID: 37577308; PMCID: PMC10413034. 14: Takakura T, Yamamoto N. [Treatment of Non-Small Cell Lung Cancer with HER2 Alterations]. Gan To Kagaku Ryoho. 2023 Jul;50(7):768-772. Japanese. PMID: 37496218. 15: Borm FJ, Smit EF. Poziotinib for HER2 Exon 20-Mutated NSCLC: Addition or Burden to the Therapeutic Arsenal? J Thorac Oncol. 2023 Aug;18(8):964-966. doi: 10.1016/j.jtho.2023.05.002. PMID: 37479324. 16: Marín A, Mamun AA, Patel H, Akamatsu H, Ye D, Sudhan DR, Eli L, Marcelain K, Brown BP, Meiler J, Arteaga CL, Hanker AB. Acquired Secondary HER2 Mutations Enhance HER2/MAPK Signaling and Promote Resistance to HER2 Kinase Inhibition in Breast Cancer. Cancer Res. 2023 Sep 15;83(18):3145-3158. doi: 10.1158/0008-5472.CAN-22-3617. PMID: 37404061; PMCID: PMC10530374. 17: Wang S, Xia M, Wang Y, Lu Z, Geng P, Dai D, Zhou Y, Wu Q. Inhibitory effect of Schisandrin on the pharmacokinetics of poziotinib in vivo and in vitro by UPLC-MS/MS. Thorac Cancer. 2023 May;14(14):1276-1285. doi: 10.1111/1759-7714.14870. Epub 2023 Mar 27. PMID: 36973912; PMCID: PMC10175034. 18: Cornelissen R, Prelaj A, Sun S, Baik C, Wollner M, Haura EB, Mamdani H, Riess JW, Cappuzzo F, Garassino MC, Heymach JV, Socinski MA, Leu SY, Bhat G, Lebel F, Le X; ZENITH20-4 Investigators. Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open- Label, Phase 2 Trial (Cohort 4). J Thorac Oncol. 2023 Aug;18(8):1031-1041. doi: 10.1016/j.jtho.2023.03.016. Epub 2023 Mar 21. PMID: 36958688. 19: David GM, Maria Del Pilar BC, Cristina MR. New therapies in non-small cell lung cancer with EGFR exon 20 insertion mutations. J Oncol Pharm Pract. 2023 Jun;29(4):934-943. doi: 10.1177/10781552231162545. Epub 2023 Mar 14. PMID: 36916182. 20: Cui Y, Wang R, Wei Y, Hou F, Li H, Jiang Y, Sun Y, Fu S, Zuo L, Wang X, Li M, Li J, Liu N, Zhang K, Wei M, Yang G. Structure optimization and discovery of novel compound for the treatment of insertion mutations within exon 20 of EGFR and HER2. Bioorg Med Chem. 2023 Mar 1;81:117202. doi: 10.1016/j.bmc.2023.117202. Epub 2023 Feb 11. PMID: 36804726.