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MedKoo Cat#: 333023 | Name: Neratinib maleate
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Description:

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

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.

Chemical Structure

Neratinib maleate
Neratinib maleate
CAS#915942-22-2 (maleate)

Theoretical Analysis

MedKoo Cat#: 333023

Name: Neratinib maleate

CAS#: 915942-22-2 (maleate)

Chemical Formula: C34H33ClN6O7

Exact Mass: 0.0000

Molecular Weight: 673.12

Elemental Analysis: C, 60.67; H, 4.94; Cl, 5.27; N, 12.49; O, 16.64

Price and Availability

Size Price Availability Quantity
200mg USD 250.00 2 Weeks
500mg USD 450.00 2 Weeks
1g USD 750.00 2 Weeks
2g USD 1,250.00 2 Weeks
5g USD 2,450.00 2 Weeks
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Related CAS #
698387-09-6 (free base) 915942-22-2 (maleate)
Synonym
HKI272; HKI 272; HKI-272; PB272; PB 272; PB-272; Neratinib; Neratinib maleate; 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 maleate
InChi Key
VXZCUHNJXSIJIM-MEBGWEOYSA-N
InChi Code
InChI=1S/C30H29ClN6O3.C4H4O4/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;5-3(6)1-2-4(7)8/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38);1-2H,(H,5,6)(H,7,8)/b9-7+;2-1-
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.O=C(O)/C=C\C(O)=O
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:
Neratinib (HKI-272) maleate is an orally available, irreversible, highly selective HER2 and EGFR inhibitor with IC50s of 59 nM and 92 nM.
In vitro activity:
It was noted that Neratinib notably mitigated cell viability and proliferation, cut down Ki67 and proliferating cell nuclear antigen expression. Moreover, Neratinib hindered cell cycle at G0/G1 phase whereas exacerbated apoptosis. ROS, MDA and Fe2+ activities were elevated by Neratinib, coupled with the reduced glutathione peroxidase 4, ferritin heavy chain 1 expression and enhanced acyl-CoA synthetase long-chain family member 4 expression. Reference: Drug Dev Res. 2022 Nov;83(7):1641-1653. https://pubmed.ncbi.nlm.nih.gov/36031759/
In vivo activity:
This study elucidated the anti-fibrotic effects of neratinib in hepatic stellate cells (HSCs) and in vivo mouse models of CCl4-induced liver fibrosis. In vivo study results indicated that neratinib inhibited the inflammatory response, HSC differentiation, and collagen accumulation induced by CCl4. Moreover, the anti-fibrotic effects of neratinib were not associated with the HER2 signaling pathways. Reference: Sci Rep. 2020 Sep 8;10(1):14756. https://pubmed.ncbi.nlm.nih.gov/32901093/

Preparing Stock Solutions

The following data is based on the product molecular weight 673.12 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. Ma H, Liu Y, Miao Z, Cheng S, Zhu Y, Wu Y, Fan X, Yang J, Li X, Guo L. Neratinib inhibits proliferation and promotes apoptosis of acute myeloid leukemia cells by activating autophagy-dependent ferroptosis. Drug Dev Res. 2022 Nov;83(7):1641-1653. doi: 10.1002/ddr.21983. Epub 2022 Aug 28. PMID: 36031759. 2. Qiu J, Jiang T, Yang G, Gong Y, Zhang W, Zheng X, Hong Z, Chen H. Neratinib exerts dual effects on cartilage degradation and osteoclast production in Osteoarthritis by inhibiting the activation of the MAPK/NF-κB signaling pathways. Biochem Pharmacol. 2022 Nov;205:115155. doi: 10.1016/j.bcp.2022.115155. Epub 2022 Jul 9. PMID: 35820500. 3. Park YJ, An HT, Park JS, Park O, Duh AJ, Kim K, Chung KH, Lee KC, Oh Y, Lee S. Tyrosine kinase inhibitor neratinib attenuates liver fibrosis by targeting activated hepatic stellate cells. Sci Rep. 2020 Sep 8;10(1):14756. doi: 10.1038/s41598-020-71688-2. PMID: 32901093; PMCID: PMC7479613. 4. 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 vitro protocol:
1. Ma H, Liu Y, Miao Z, Cheng S, Zhu Y, Wu Y, Fan X, Yang J, Li X, Guo L. Neratinib inhibits proliferation and promotes apoptosis of acute myeloid leukemia cells by activating autophagy-dependent ferroptosis. Drug Dev Res. 2022 Nov;83(7):1641-1653. doi: 10.1002/ddr.21983. Epub 2022 Aug 28. PMID: 36031759. 2. Qiu J, Jiang T, Yang G, Gong Y, Zhang W, Zheng X, Hong Z, Chen H. Neratinib exerts dual effects on cartilage degradation and osteoclast production in Osteoarthritis by inhibiting the activation of the MAPK/NF-κB signaling pathways. Biochem Pharmacol. 2022 Nov;205:115155. doi: 10.1016/j.bcp.2022.115155. Epub 2022 Jul 9. PMID: 35820500.
In vivo protocol:
1. Park YJ, An HT, Park JS, Park O, Duh AJ, Kim K, Chung KH, Lee KC, Oh Y, Lee S. Tyrosine kinase inhibitor neratinib attenuates liver fibrosis by targeting activated hepatic stellate cells. Sci Rep. 2020 Sep 8;10(1):14756. doi: 10.1038/s41598-020-71688-2. PMID: 32901093; PMCID: PMC7479613. 2. 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.
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. 2: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548937/ PubMed PMID: 31644242. 3: Booth LA, Roberts JL, Dent P. The role of cell signaling in the crosstalk between autophagy and apoptosis in the regulation of tumor cell survival in response to sorafenib and neratinib. Semin Cancer Biol. 2019 Oct 20. pii: S1044-579X(19)30024-0. doi: 10.1016/j.semcancer.2019.10.013. [Epub ahead of print] Review. PubMed PMID: 31644944. 4: Miles J, White Y. Neratinib for the Treatment of Early-Stage HER2-Positive Breast Cancer. J Adv Pract Oncol. 2018 Nov-Dec;9(7):750-754. Epub 2018 Nov 1. Review. PubMed PMID: 31249722; PubMed Central PMCID: PMC6570523. 5: Collins DM, Conlon NT, Kannan S, Verma CS, Eli LD, Lalani AS, Crown J. Preclinical Characteristics of the Irreversible Pan-HER Kinase Inhibitor Neratinib Compared with Lapatinib: Implications for the Treatment of HER2-Positive and HER2-Mutated Breast Cancer. Cancers (Basel). 2019 May 28;11(6). pii: E737. doi: 10.3390/cancers11060737. Review. PubMed PMID: 31141894; PubMed Central PMCID: PMC6628314. 6: Deeks ED. Neratinib: First Global Approval. Drugs. 2017 Oct;77(15):1695-1704. doi: 10.1007/s40265-017-0811-4. Review. PubMed PMID: 28884417. 7: Kourie HR, El Rassy E, Clatot F, de Azambuja E, Lambertini M. Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib. Onco Targets Ther. 2017 Jul 10;10:3363-3372. doi: 10.2147/OTT.S122397. eCollection 2017. Review. PubMed PMID: 28744140; PubMed Central PMCID: PMC5513878. 8: Echavarria I, López-Tarruella S, Márquez-Rodas I, Jerez Y, Martin M. Neratinib for the treatment of HER2-positive early stage breast cancer. Expert Rev Anticancer Ther. 2017 Aug;17(8):669-679. doi: 10.1080/14737140.2017.1338954. Epub 2017 Jun 26. Review. PubMed PMID: 28649882. 9: Chan A. Neratinib in HER-2-positive breast cancer: results to date and clinical usefulness. Ther Adv Med Oncol. 2016 Sep;8(5):339-50. doi: 10.1177/1758834016656494. Epub 2016 Jul 10. Review. PubMed PMID: 27583026; PubMed Central PMCID: PMC4981294. 10: Tiwari SR, Mishra P, Abraham J. Neratinib, A Novel HER2-Targeted Tyrosine Kinase Inhibitor. Clin Breast Cancer. 2016 Oct;16(5):344-348. doi: 10.1016/j.clbc.2016.05.016. Epub 2016 May 29. Review. PubMed PMID: 27405796. 11: Kourie HR, Chaix M, Gombos A, Aftimos P, Awada A. Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations. Expert Opin Drug Metab Toxicol. 2016 Aug;12(8):947-57. doi: 10.1080/17425255.2016.1198317. Epub 2016 Jun 27. Review. PubMed PMID: 27284682. 12: Segovia-Mendoza M, González-González ME, Barrera D, Díaz L, García-Becerra R. Efficacy and mechanism of action of the tyrosine kinase inhibitors gefitinib, lapatinib and neratinib in the treatment of HER2-positive breast cancer: preclinical and clinical evidence. Am J Cancer Res. 2015 Aug 15;5(9):2531-61. eCollection 2015. Review. PubMed PMID: 26609467; PubMed Central PMCID: PMC4633889. 13: Feldinger K, Kong A. Profile of neratinib and its potential in the treatment of breast cancer. Breast Cancer (Dove Med Press). 2015 Jun 9;7:147-62. doi: 10.2147/BCTT.S54414. eCollection 2015. Review. PubMed PMID: 26089701; PubMed Central PMCID: PMC4467661. 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.