Poziotinib HCl | CAS#1429757-68-5

MedKoo Cat#: 533571 | Name: Poziotinib HCl

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 HCl

CAS#1429757-68-5 (HCl)

Theoretical Analysis

MedKoo Cat#: 533571

Name: Poziotinib HCl

CAS#: 1429757-68-5 (HCl)

Chemical Formula: C23H22Cl3FN4O3

Exact Mass: 526.0742

Molecular Weight: 527.80

Elemental Analysis: C, 52.34; H, 4.20; Cl, 20.15; F, 3.60; N, 10.62; O, 9.09

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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

Poziotinib hydrochloride; Poziotinib HCl; HM781-36B; HM78136B; HM-78136B; HM 78136B; NOV120101; NOV-120101; NOV 120101; Poziotinib

IUPAC/Chemical Name

1-[4-[4-(3,4-Dichloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]prop-2-en-1-one hydrochloride

InChi Key

OMYSOLOMWJFVNK-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H21Cl2FN4O3.ClH/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);1H

SMILES Code

C=CC(N1CCC(OC2=CC3=C(NC4=CC=C(Cl)C(Cl)=C4F)N=CN=C3C=C2OC)CC1)=O.[H]Cl

Appearance

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

Shelf Life

>3 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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Poziotinib, also known as HM781-36B and NOV120101, is an orally bioavailable, quinazoline-based pan epidermal growth factor receptor (EGFR or HER) inhibitor.

In vitro activity:

Mechanistic studies indicated that poziotinib increases the intracellular accumulation of the ABCB1 transporter substrates, paclitaxel and doxorubicin, and the ABCG2 transporter substrates, mitoxantrone and SN-38, by inhibiting their substrate efflux function. Accumulation assay results suggested that poziotinib binds reversibly to the ABCG2 and ABCB1 transporter. Furthermore, western blot experiments indicated that poziotinib, at 0.6 μM, significantly downregulates the expression of the ABCG2 but not the ABCB1 transporter protein, suggesting that the ABCG2 reversal effect produced by poziotinib is due to transporter downregulation and inhibition of substrate efflux. Poziotinib concentration-dependently stimulated the ATPase activity of both ABCB1 and ABCG2, with EC50 values of 0.02 μM and 0.21 μM, respectively, suggesting that it interacts with the drug-substrate binding site. Reference: Cancers (Basel). 2020 Nov 4;12(11):3249. https://pubmed.ncbi.nlm.nih.gov/33158067/

In vivo activity:

To further assess the efficacy of poziotinib in the metastatic setting, this study analyzed by ex vivo BL imaging the lungs and ovaries from L755S-bearing mice that had been treated for 7 weeks (Fig. 3E). Surprisingly, in the experimental model, neratinib was ineffective in reducing ovary metastasis. However, mice treated with poziotinib alone or in combination with fulvestrant had no evidence of lung or ovary metastasis (Fig. 3F; Table 3). To analyze the short term in vivo efficacy of poziotinib, this study generated HER2 L755S MIND xenografts (MM134) and monitored primary tumors until radiance reached 1 × 109 by BL imaging. This study analyzed signaling of these tumors by immunoblotting and found that poziotinib reduced the levels of phospho-HER2, phospho-Akt, phospho-p44/42 MAPK, phospho-mTOR, and phospho-S6, suggesting that poziotinib can inhibit L755S-induced orthotopic tumor growth, oncogenic signaling, and ovary metastasis even with a short duration of treatment (Supplementary Fig. S7E). Taken together, these data clearly suggest that poziotinib may be useful for the treatment of HER2-mutant metastatic ILC. Reference: Cancer Res. 2022 Aug 16;82(16):2928-2939. https://pubmed.ncbi.nlm.nih.gov/35736563/

Preparing Stock Solutions

The following data is based on the product molecular weight 527.80 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.

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. Zhang Y, Wu ZX, Yang Y, Wang JQ, Li J, Sun Z, Teng QX, Ashby CR Jr, Yang DH. Poziotinib Inhibits the Efflux Activity of the ABCB1 and ABCG2 Transporters and the Expression of the ABCG2 Transporter Protein in Multidrug Resistant Colon Cancer Cells. Cancers (Basel). 2020 Nov 4;12(11):3249. doi: 10.3390/cancers12113249. PMID: 33158067; PMCID: PMC7694178. 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. 3. Kalra R, Chen CH, Wang J, Salam AB, Dobrolecki LE, Lewis A, Sallas C, Yates CC, Gutierrez C, Karanam B, Anurag M, Lim B, Ellis MJ, Kavuri SM. Poziotinib Inhibits HER2-Mutant-Driven Therapeutic Resistance and Multiorgan Metastasis in Breast Cancer. Cancer Res. 2022 Aug 16;82(16):2928-2939. doi: 10.1158/0008-5472.CAN-21-3106. PMID: 35736563; PMCID: PMC9379360. 4. Wang J, Chen F, Jiang H, Xu J, Meng D, Geng P, Dai D, Hu J, Zhou Y, Zhou Q, Wang S. Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes In Vivo and in an In Vitro Cocktail Method. Front Pharmacol. 2021 Jan 5;11:593518. doi: 10.3389/fphar.2020.593518. PMID: 33746741; PMCID: PMC7970697.

In vitro protocol:

In vivo protocol:

1. Kalra R, Chen CH, Wang J, Salam AB, Dobrolecki LE, Lewis A, Sallas C, Yates CC, Gutierrez C, Karanam B, Anurag M, Lim B, Ellis MJ, Kavuri SM. Poziotinib Inhibits HER2-Mutant-Driven Therapeutic Resistance and Multiorgan Metastasis in Breast Cancer. Cancer Res. 2022 Aug 16;82(16):2928-2939. doi: 10.1158/0008-5472.CAN-21-3106. PMID: 35736563; PMCID: PMC9379360. 2. Wang J, Chen F, Jiang H, Xu J, Meng D, Geng P, Dai D, Hu J, Zhou Y, Zhou Q, Wang S. Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes In Vivo and in an In Vitro Cocktail Method. Front Pharmacol. 2021 Jan 5;11:593518. doi: 10.3389/fphar.2020.593518. PMID: 33746741; PMCID: PMC7970697.