Neratinib API Manufacturer in India

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Neratinib API

Neratinib is a synthetic irreversible tyrosine kinase inhibitor (TKI) and antineoplastic pharmaceutical active pharmaceutical ingredient (API). It belongs to the quinoline-based kinase inhibitor class and acts primarily against the HER2 (ErbB2), EGFR (ErbB1), and HER4 (ErbB4) receptor tyrosine kinases.

Neratinib is used as an active pharmaceutical ingredient in the development and manufacture of pharmaceutical formulations for HER2-positive breast cancer. It was developed under the code HKI-272 and is marketed as an oral anticancer medicine.

Neratinib API Manufacturer in India

Neratinib is a specialized oncology pharmaceutical API relevant to targeted cancer therapy, kinase inhibitor research, pharmaceutical formulation development and analytical quality control.

The API is particularly relevant to pharmaceutical research involving HER2 signaling, epidermal growth factor receptor pathways, breast cancer and targeted antineoplastic drug development.

Chemical Information

CAS Number: 698387-09-6

Molecular Formula: C₃₀H₂₉ClN₆O₃

Molecular Weight: 557.0 g/mol

Chemical Name: (E)-N-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide

Development Code: HKI-272

Drug Class: Tyrosine Kinase Inhibitor

Therapeutic Class: Antineoplastic Agent

Therapeutic Area: Oncology

Molecule Type: Synthetic Small Molecule

Target: EGFR / HER2 / HER4

PubChem identifies Neratinib with CAS 698387-09-6, molecular formula C₃₀H₂₉ClN₆O₃ and molecular weight 557.0 g/mol.

Mechanism of Action

Neratinib is an irreversible pan-ErbB tyrosine kinase inhibitor.

Its mechanism includes:

  • Irreversible inhibition of EGFR
  • Irreversible inhibition of HER2
  • Inhibition of HER4 signaling
  • Binding to catalytic kinase domains
  • Suppression of receptor tyrosine kinase phosphorylation
  • Reduction of downstream oncogenic signaling
  • Modulation of MAPK and PI3K/AKT signaling pathways

Neratinib forms a covalent interaction with cysteine residues in the kinase domains of HER-family receptors, producing prolonged inhibition of receptor signaling.

Pharmaceutical Applications

Neratinib API is relevant to:

  • HER2-positive breast cancer formulations
  • Oncology drug development
  • Targeted cancer therapy
  • Tyrosine kinase inhibitor research
  • HER2 signaling research
  • EGFR inhibitor research
  • HER4 signaling research
  • Antineoplastic pharmaceutical development
  • Pharmaceutical formulation development
  • Pharmaceutical API manufacturing
  • Analytical and quality-control testing

Oncology Applications

Neratinib is particularly associated with HER2-positive breast cancer and has been approved as an extended adjuvant treatment for certain patients with early-stage HER2-positive breast cancer.

Its activity against HER-family receptor tyrosine kinases makes it an important molecule in targeted oncology research.

HER2 Targeting

HER2 is a receptor tyrosine kinase involved in cellular growth and proliferation. Abnormal HER2 signaling can contribute to the development and progression of certain cancers.

Neratinib irreversibly inhibits HER2 kinase activity, thereby reducing downstream signaling involved in tumor-cell proliferation and survival.

Physical Characteristics

Neratinib is a synthetic organic small molecule with molecular formula C₃₀H₂₉ClN₆O₃ and molecular weight 557.0 g/mol. PubChem reports an XLogP3-AA value of approximately 4.9 and topological polar surface area of approximately 112 Ų.

Neratinib is also commercially encountered in the maleate salt form. Neratinib Maleate has CAS 915942-22-2, while Neratinib Maleate Monohydrate has CAS 1144516-12-0. These should not be confused with the free-base Neratinib API.

Manufacturing Process

A controlled Neratinib API manufacturing process may involve:

  1. Qualification of starting materials
  2. Preparation of substituted quinoline intermediates
  3. Construction of the quinoline core
  4. Introduction of the cyano functionality
  5. Preparation of substituted aniline intermediates
  6. Controlled coupling reactions
  7. Formation of the acrylamide side chain
  8. Introduction of the dimethylamino group
  9. Purification
  10. Crystallization
  11. Filtration and washing
  12. Controlled drying
  13. Final analytical testing
  14. GMP-compliant packaging

Quality Control Testing

Typical Neratinib API testing may include:

  • Identification by IR
  • HPLC identification
  • Assay by HPLC
  • Related substances
  • Degradation products
  • Residual solvents
  • Water content
  • Residue on ignition
  • Elemental impurities
  • Particle-size distribution, where applicable
  • Stability testing

Because Neratinib contains a defined E-configured acrylamide moiety, appropriate control of chemical identity and related substances is important during API quality assessment.

Storage

Store Neratinib API in a tightly closed container under controlled pharmaceutical storage conditions, protected from excessive moisture, heat and direct light.

Commercial storage conditions should be established according to validated stability data and the applicable API specification.

Detailed Specifications

Parameter Specification
Appearance White crystalline powder or crystals
Identification IR & HPLC compliant
Assay (HPLC) 98.0% – 102.0%
Loss on Drying NMT 1.0%
Residue on Ignition NMT 0.5%
Individual Impurity NMT 0.5%
Total Impurities ≤ 1.5%
Water Content NMT 1.0%
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