WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H201470
CAS#: 698387-09-6 (free base)
Description: Neratinib, also known as HKI-272 or PB272, is an orally available, irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor.
Hodoodo Cat#: H201470
Name: Neratinib
CAS#: 698387-09-6 (free base)
Chemical Formula: C30H29ClN6O3
Exact Mass: 556.20
Molecular Weight: 557.040
Elemental Analysis: C, 64.68; H, 5.25; Cl, 6.36; N, 15.09; O, 8.62
Related CAS #: 698387-09-6 (free base) 915942-22-2 (maleate)
Synonym: HKI272; HKI 272; HKI-272; PB272; PB 272; PB-272; Neratinib; Nerlynx
IUPAC/Chemical Name: (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide
InChi Key: JWNPDZNEKVCWMY-VQHVLOKHSA-N
InChi Code: InChI=1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+
SMILES Code: O=C(NC1=C(OCC)C=C2N=CC(C#N)=C(NC3=CC=C(OCC4=NC=CC=C4)C(Cl)=C3)C2=C1)/C=C/CN(C)C
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, 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: HKI-272 is a potent inhibitor of HER-2 and is highly active against HER-2-overexpressing human breast cancer cell lines in vitro. It also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells. HKI-272 reduces HER-2 receptor autophosphorylation in cells at doses consistent with inhibition of cell proliferation and functions as an irreversible binding inhibitor, most likely by targeting a cysteine residue in the ATP-binding pocket of the receptor. In agreement with the predicted effects of HER-2 inactivation, HKI-272 treatment of cells results in inhibition of downstream signal transduction events and cell cycle regulatory pathways.
| Biological target: | Neratinib (HKI-272) is an irreversible tyrosine kinase inhibitor with IC50s of 59 nM and 92 nM for HER2 and EGFR, respectively. |
| In vitro activity: | The efficacy of neratinib in the treatment of HER2 amplified carcinosarcoma was determined in vitro using seven primary carcinosarcoma cell lines with differential expression of HER2/neu. Two of seven (28.5%) carcinosarcoma cell lines were HER2/neu amplified. HER2/neu amplified cell lines SARARK6 and SARARK9 were significantly more sensitive to neratinib than the five non-HER2/neu amplified carcinosarcoma cell lines (mean±SEM IC50: 0.014μM±0.004 vs. 0.164μM±0.019 p=0.0003). Neratinib treatment caused a significant build up in G0/G1 phase of the cell cycle, arrest auto phosphorylation of HER2/neu and activation of S6. Reference: Gynecol Oncol. 2015 Oct;139(1):112-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587290/ |
| In vivo activity: | Neratinib’s effect in vivo was determined by establishing HER2/neu amplified xenografts of SARARK 6. When subcutaneous tumors reached at least 0.5 cm in a single dimension treatment was initiated. Of the 10 mice injected with SARARK6, a total of nine mice developed subcutaneous tumors. Of the nine mice available, 4 were considered vehicle and 5 were started on neratinib 40mg/kg 5 days weekly by oral gavage. Over the course of 40 days mice tolerated treatment with neratinib well and gained weight at a similar rate compared to vehicle treated controls (data not shown). Treatment with neratinib significantly inhibited tumor growth as early as 9 days after treatment began (p=0.012). Over the course of the treatment period neratinib significantly inhibited tumor growth with the greatest difference noted at 30 days (p |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 2.0 | 3.60 |
The following data is based on the product molecular weight 557.04 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. Ardestani A, Li S, Annamalai K, Lupse B, Geravandi S, Dobrowolski A, Yu S, Zhu S, Baguley TD, Surakattula M, Oetjen J, Hauberg-Lotte L, Herranz R, Awal S, Altenhofen D, Nguyen-Tran V, Joseph S, Schultz PG, Chatterjee AK, Rogers N, Tremblay MS, Shen W, Maedler K. Neratinib protects pancreatic beta cells in diabetes. Nat Commun. 2019 Nov 1;10(1):5015. doi: 10.1038/s41467-019-12880-5. PMID: 31676778; PMCID: PMC6825211. 2. Nagpal A, Redvers RP, Ling X, Ayton S, Fuentes M, Tavancheh E, Diala I, Lalani A, Loi S, David S, Anderson RL, Smith Y, Merino D, Denoyer D, Pouliot N. Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2+ve breast cancer metastasis. Breast Cancer Res. 2019 Aug 13;21(1):94. doi: 10.1186/s13058-019-1177-1. PMID: 31409375; PMCID: PMC6693253. |
| In vitro protocol: | 1. Ardestani A, Li S, Annamalai K, Lupse B, Geravandi S, Dobrowolski A, Yu S, Zhu S, Baguley TD, Surakattula M, Oetjen J, Hauberg-Lotte L, Herranz R, Awal S, Altenhofen D, Nguyen-Tran V, Joseph S, Schultz PG, Chatterjee AK, Rogers N, Tremblay MS, Shen W, Maedler K. Neratinib protects pancreatic beta cells in diabetes. Nat Commun. 2019 Nov 1;10(1):5015. doi: 10.1038/s41467-019-12880-5. PMID: 31676778; PMCID: PMC6825211. |
| In vivo protocol: | 1. Nagpal A, Redvers RP, Ling X, Ayton S, Fuentes M, Tavancheh E, Diala I, Lalani A, Loi S, David S, Anderson RL, Smith Y, Merino D, Denoyer D, Pouliot N. Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2+ve breast cancer metastasis. Breast Cancer Res. 2019 Aug 13;21(1):94. doi: 10.1186/s13058-019-1177-1. PMID: 31409375; PMCID: PMC6693253. |
1: Xuhong JC, Qi XW, Zhang Y, Jiang J. Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer. Am J Cancer Res. 2019 Oct 1;9(10):2103-2119. eCollection 2019. Review. PubMed PMID: 31720077; PubMed Central PMCID: PMC6834479.
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14: López-Tarruella S, Jerez Y, Márquez-Rodas I, Martín M. Neratinib (HKI-272) in the treatment of breast cancer. Future Oncol. 2012 Jun;8(6):671-81. doi: 10.2217/fon.12.66. Review. PubMed PMID: 22764764.
15: Bose P, Ozer H. Neratinib: an oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Expert Opin Investig Drugs. 2009 Nov;18(11):1735-51. doi: 10.1517/13543780903305428. Review. PubMed PMID: 19780706.
