216974-75-3

Basic information

• Product Name: Avastin
• Synonyms: Avastin;Anti-vegf monoclonal antibody;Bevacizumab;Immunoglobulin G1, anti-(human vascular endothelial growth factor) (human-mouse monoclonal rhumab-vegf gamma1-chain), disulfide with human-mouse monoclonal rhumab-vegf light chain, dimer;Rhumab-vegf;Unii-2S9zzm9Q9v;Avastatin;Bevacituzumab
• CAS NO: 216974-75-3
• Molecular Formula: C6638H10160N1720O2108S44
• Mol File: 216974-75-3.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Avastin(CAS DataBase Reference)
• NIST Chemistry Reference: Avastin(216974-75-3)
• EPA Substance Registry System: Avastin(216974-75-3)

Safety Data

• Hazardous Substances Data: 216974-75-3(Hazardous Substances Data)

Usage

Description

Avastin, also known as Bevacizumab, is a humanized IgG1 monoclonal antibody against vascular endothelial growth factor (VEGF). It is engineered by incorporating the VEGF binding residues of the murine neutralizing antibody A.4.6.1 into the framework of the consensus human IgG1. Bevacizumab's amino acid sequence is approximately 93% human IgG and 7% murine antibody, and it is produced in a CHO cell expression system. It functions by inhibiting tumor angiogenesis and delaying disease progression.

Uses

Used in Oncology:
Avastin is used as an anticancer agent for various types of cancer. It is particularly effective against solid malignancies such as metastatic colorectal cancer, non-small cell lung cancer, renal cell carcinoma, and certain types of brain cancer. Avastin works by binding to VEGF with high affinity, preventing its interaction with tyrosine kinase receptors VEGFR1 and VEGFR2 on the surface of endothelial cells. This action inhibits cell proliferation and microvascular growth, blocking the growth of tumor xenografts and reducing the size and number of metastases.
Used in Combination Therapy:
Avastin is often used in combination with other chemotherapeutic drugs, such as fluorouracil and leucovorin, to enhance chemo-sensitivity and efficacy in resistant cases. This combination therapy has been shown to significantly increase median overall survival, progression-free survival, overall response rate, and duration of response in clinical studies.
Used in Intravenous Infusion:
The recommended dosage of Avastin is 5 mg/kg administered once every 2 weeks as an intravenous infusion until disease progression is detected. This method of administration ensures that the drug is directly introduced into the bloodstream, allowing for a controlled release and distribution throughout the body.
Used in Drug Delivery Systems:
To overcome the limitations of Avastin, such as low clearance and variability with body weight, gender, and tumor burden, novel drug delivery systems have been developed. These systems aim to improve the delivery, bioavailability, and therapeutic outcomes of the drug by employing various organic and metallic nanoparticles as carriers for Avastin delivery.
Brand name: Avastin

Originator

Genentech (US)

Clinical Use

Monoclonal antibody: Treatment of colorectal cancer Treatment of breast cancer Treatment of renal cell carcinoma Treatment of lung cancer Treatment of ovarian, fallopian tube or peritoneal cancer

Enzyme inhibitor

This humanized monoclonal antibody (MW = 149.2 kDa; CAS 216974-75- 3), known by the tradename Avastinò, is an angiogenesis inhibitor that targets vascular endothelial growth factor A (VEGF-A). Because VEGF is the key angiogenic factor in tumors, blocking VEGF signal transduction can lead to tumor growth arrest and inhibition of metastasis. The rationale for Avastin therapy is premised on findings that high VEGF expression correlates with (a) reduced overall survival, (b) disease progression, (c) greater risk of relapse, (d) lymph node involvement, and (e) malignant pleural effusion. By binding directly bind to VEGF-A, Avastin blocks its interaction with endothelial cell VEGF receptors, thereby inhibiting neovascularization and depriving cancer cells of vital nutrients and oxygen. Avastin is approved for: metastatic colorectal cancer (mCRC), when started with the first or second intravenous 5-FU–based chemotherapy for metastatic cancer; advanced-stage nonsquamous, non–small cell lung cancer (NSCLC), when administered in combination with carboplatin and paclitaxel in patients who have not received chemotherapy for their advanced disease; metastatic renal cell cancer (mRCC) when used with interferon-a; and glioblastoma multiforme (GBM) in adult patients whose cancer has progressed after prior treatment.

target

Angiogenesis is important for tumour growth and metastasis, and is an important target for new biological agents. ?Bevacizumab is a humanised recombinant antibody that prevents vascular ?endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumour growth.

Drug interactions

Potentially hazardous interactions with other drugs Bisphosphonates: increased risk of osteonecrosis of the jaw. Cytotoxics: avoid with panitumumab. Vaccines: risk of generalised infections with live vaccines - avoid.

Metabolism

Assessment of bevacizumab metabolism in rabbits following a single IV dose of 125I-bevacizumab indicated that its metabolic profile was similar to that expected for a native IgG molecule which does not bind VEGF. The metabolism and elimination of bevacizumab is similar to endogenous IgG i.e. primarily via proteolytic catabolism throughout the body, including endothelial cells, and does not rely primarily on elimination through the kidneys and liver. Binding of the IgG to the FcRn receptor results in protection from cellular metabolism and the long terminal half-life.