Unii-fys6T7F842

Base Information

• Chemical Name: Unii-fys6T7F842
• CAS No.: 331731-18-1
• Molecular Formula: C6428H9912N1694O1987S46
• Molecular Weight: 434.46288
• Mol file: 331731-18-1.mol

Synonyms:Adalimumab;D 2E7; Humira

Chemical Property of Unii-fys6T7F842

Chemical Property:

• PSA: 0.00000
• LogP: 0.00000

Purity/Quality:

99% ^*data from raw suppliers

Adalimumab ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Description: Adalimumab is the first fully human neutralizing IgG1 monoclonal antibody specific for TNF-alpha and is the third TNF sequestrant marketed. It was launched in US, UK and Germany for the treatment of rheumatoid arthritis. It prevents TNF binding to p55 and p75 cell surface TNF receptors thereby decreasing leukocyte migration and acute phase reactants such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and levels of serum IL-6, MMP-1 and MMP-3. Adalimumab was developed starting with a phage-display derived murine antibody, followed by replacement of both heavy and light chains with human forms and further optimization to yield the final humanized form. In receptor binding studies, adalimumab exhibits an IC50 between 7.8×10-11 and 15.6×10-11M with a Kd of 1×10-10 M. It also binds to pro-TNFalpha on cell membranes mediating complement-dependent toxicity and to the Fc receptor mediating antibody-dependent cytotoxicity. In a human-TNF transgenic polyarthritis mouse model, adalimumab was efficacious based upon both clinical and histological readouts. Patients responding inadequately to methotrexate were co-administered methotrexate and adalimumab, which resulted in improved ACR scores in a 52-week study (ACR20: 59%; ACR50: 42%; ACR70; 23%). Radiographic analysis at six months showed decreased progression of structural joint damage (96%＞placebo) and that joint-space narrowing stabilizes after six months. Adalimumab has an ED50 of 0.3 to 0.5 mg/kg and is dosed subcutaneously once every two weeks (0.8 mL containing 40 mg). The Vdss ranged from 0.063 to 0.76 L/kg consistent with being highly localized within the vasculature. It is slowly cleared with clearance values ranging from 0.18 to 0.27 mL/min and with a terminal half-life of about 12 days. As is the case with other TNF-alpha sequestrants, injection-site irritation is the most common side effect. The risk of developing opportunistic infection, especially tuberculosis, has been noted with TNF sequestrant biologics, which has led to screening of patients to identify those at risk.
• Uses: Treatment of rheumatoid arthritis and other chronic inflammatory diseases (monoclonal antibody).
• Indications: Adalimumab has been evaluated in a number of clinical trials for RA, Crohn's disease,ankylosing spondylitis,and psoriatic arthritis. Initially evaluated as adjunctive therapy to RA patients on methotrexate, adalimumab demonstrated rapid improvement in American College of Rheumatology 20 scores at 1 week of administration. The PREMIER trial compared combination adalimumab plus methotrexate therapy with either medication given alone and found that the combination of adalimumab plus methotrexate was superior to adalimumab or methotrexate monotherapy.
• Clinical Use: Adalimumab is supplied in single-use, prefilled, glass syringes as a sterile, preservative-free, colorless solution for subcutaneous administration. The pharmacokinetics of adalimumab were linear over the dose range of 0.5 to 10.0 mg/kg following a single IV dose. The mean elimination half-life was approximately 2 weeks.
• Drug interactions: Adalimumab is currently approved for RA and psoriatic arthritis in combination with methotrexate and low-dose prednisone. Live viruses should be avoided in patients on adalimumab and its use may decrease the immunologic protection conferred by live attenuated vaccines. No clear data are available for its use in combination with other biologic agents, so this combination should be avoided until further studies have demonstrated efficacy and safety.