Trastuzumab Chemical Properties

storage temp. 

Store at -20°C

form 

Solid

color 

White to light yellow

InChI

InChI=1/C10H14N6O5/c11-9-14-6-3(7(20)15-9)13-10(12)16(6)8-5(19)4(18)2(1-17)21-8/h2,4-5,8,17-19H,1H2,(H2,12,13)(H3,11,14,15,20)/t2-,4-,5-,8-/s3

InChIKey

FNXPTCITVCRFRK-MIUWUGMQNA-N

SMILES

N1C2=C(NC(N)=NC2=O)N([C@H]2[C@H](O)[C@H](O)[C@@H](CO)O2)C=1N |&1:10,11,13,15,r|

Safety Information

Hazardous Substances Data

180288-69-1(Hazardous Substances Data)

Trastuzumab Usage And Synthesis

History

Trastuzumab, marketed as Herceptin, is a humanized monoclonal antibody whose history is a paradigm of breakthroughs in targeted therapy in oncology. Its development involves a close integration of basic scientific discoveries, clinical validation, and drug engineering. The story begins in the mid-1980s when Axel Ullrich, in his research team at Genentech, successfully cloned the HER2 (human epidermal growth factor receptor 2) gene, revealing its role in cell growth and proliferation. Subsequently, research by Dennis J. Slamon at UCLA showed that the HER2 gene was amplified and overexpressed in approximately 25% to 30% of breast cancer patients, and this overexpression was significantly associated with disease aggressiveness, high recurrence rates, and poor prognosis. This discovery provided a clear molecular target for targeted therapy. Subsequently, Genentech scientists, particularly H. Michael Shepard and colleagues, developed a monoclonal antibody that specifically binds to and blocks the activity of the HER2 receptor based on this target. Through drug engineering optimization, trastuzumab was finally developed, which can effectively inhibit the growth of HER2-overexpressing tumor cells. After years of clinical trials, trastuzumab was approved by the U.S. Food and Drug Administration (FDA) on September 25, 1998, for the treatment of HER2-positive metastatic breast cancer.

Uses

Trastuzumab is used to treat breast cancer. It is effective against tumors that overexpress the HER2/neu protien. As part of chemotherapy regimen for adjuvant treatment of lymph-node positive, HER2/neu positive cancer.

Indications

The introduction of herceptin (Trastuzumab) into clinical practice for the treatment of breast cancer marks a major advance in the use of monoclonal antibody cancer therapy. Herceptin is a humanized antibody directed against the HER-2 antigen that is overexpressed on the tumor cell surface in approximately 25% of breast cancer patients. HER-2/neu/erbB2 overexpression marks an aggressive estrogen receptor–negative form of breast cancer. Therefore, a therapeutic agent selective for this target is particularly valuable. Herceptin is administered by intravenous infusion and in conjunction with paclitaxel can extend survival in patients with HER-2/neu/erbB2 overexpressing metastatic breast cancer.Herceptin use is associated with infusion- related hypotension, flushing and bronchoconstriction, and skin rash but no bone marrow toxicity. Herceptin appears to sensitize patients to cardiotoxicity, an important concern in patients also receiving doxorubicin.

Definition

Herceptin (generic name: trastuzumab) is not a chemo drug, it is a targeted therapy anticancer drug.
Herceptin contains one active ingredient, trastuzumab, and is given as an intravenous (IV) infusion slowly into a vein. Herceptin Hylecta contains two active ingredients, trastuzumab and hyaluronidase-oysk, and is given as a subcutaneous injection, which is an injection that goes under the skin.

Mechanism of action

Trastuzumab is a monoclonal antibody against human epidermal growth factor receptor 2 (HER2). Trastuzumab binds to an extracellular domain of this receptor and inhibits HER2 homodimerization, thereby preventing HER2-mediated signaling. It is also thought to facilitate antibody-dependent cellular cytotoxicity, leading to the death of cells that express HER2. Its mechanism differs slightly from that of the newer agent pertuzumab; the latter inhibits hetero-dimerization of HER2 with HER3, a related growth factor receptor. Trastuzumab has been shown to bind three distinct regions of domain IV of the HER2 extracellular domain through electrostatic and hydrophobic bindings[1].

References

[1] Hamid Maadi. “Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma.” Cancers (2021).

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