Obinutuzumab
- Product NameObinutuzumab
- CAS949142-50-1
- CBNumberCB81518489
- MW0
- MDL NumberMFCD00211769
- MOL FileMol file
Chemical Properties
| form | Liquid |
| color | Colorless to light yellow |
Safety
| Hazardous Substances Data | 949142-50-1(Hazardous Substances Data) |
Obinutuzumab Chemical Properties,Usage,Production
Description
In November 2013, the US FDA approved the glycoengineered, type II anti-CD20 antibody obinutuzumab (also known as GA101) in combination with chlorambucil chemotherapy for the treatment of people with previously untreated chronic lymphocytic leukemia (CLL). Obinutuzumab is the first drug approved under the FDA’s breakthrough therapy designation, created in 2012 to quicken the pace of development and review of drugs for serious conditions. The Fc portion of obinutuzumab was glycoengineered to reduce fucosylation of the Fc carbohydrate, resulting in increased FcγRIIIa affinity and antibody-dependent cellular cytotoxicity (ADCC) potency. As expected for a type II antibody, obinutuzumab demonstrated lower complement-mediated cytotoxicity, more potent mediation of cell death via the nonclassical apoptosis pathway and increased ADCC as compared with rituximab in preclinical studies. In addition, obinutuzumab induced a stronger antitumor effect in mouse xenograft models of human lymphoma than rituximab and ofatumumab, supporting clinical investigation of this third generation anti-CD20 antibody.Originator
GlycArt Biotechnology AG (United States)Uses
Obinutuzumab (GA101) a Type II CD20 humanized IgG1 monoclonal antibody in development for non-Hodgkin lymphoma.brand name
Gazyvain vivo
Obinutuzumab is more active than rituximab administered at similar doses on established RL tumors. The antitumor effect of obinutuzumab against RL xenografts is dose dependent in terms of tumor growth inhibition (TGI). TGI is calculated using NCI formula at day 34 and shows values of 25, 75, and 85% for the 10, 30, and 100 mg/kg dosages of obinutuzumab, respectively. The higher doses of 30 and 100 mg/kg of obinutuzumab significantly inhibit the growth of RL tumors and result in some complete tumor remissions (10% and 30%, respectively). Tolerability of obinutuzumab with these regimens is excellent and no significant modification of body weight is observed[2]. Obinutuzumab induces a strong antitumor effect, including complete tumor remission in the SU-DHL4 model and overall superior efficacy compared with both rituximab and ofatumumab[1]. Obinutuzumab plus bendamustine achieves superior tumor growth inhibition versus rituximab plus bendamustine and shows a statistically significant effect versus the respective single treatments. Obinutuzumab plus chemotherapy is superior to the respective monotherapies[3].
References
[1] Herter S, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013 Oct;12(10):2031-42. DOI:10.1158/1535-7163.MCT-12-1182[2] Dalle S, et al. Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody -GA101. Mol Cancer Ther. 2011 Jan;10(1):178-85. DOI:10.1158/1535-7163.MCT-10-0385
[3] Herting F, et al. Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab(GA101) in combination with chemotherapy in xenograft models of human lymphoma. Leuk Lymphoma. 2014 Sep;55(9):2151-5160. DOI:10.3109/10428194.2013.856008
Obinutuzumab Suppliers
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