Unii-fys6T7F842

Iupac Name：2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetic acid

Molecular Weight：434.46288

Modify Date.: 2022-12-13 02:07

Introduction: Treatment of rheumatoid arthritis and other chronic inflammatory diseases (monoclonal antibody). View more+

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1. Names and Identifiers

1.1 Name: Unii-fys6T7F842
1.2 Synonyms: Adalimumab Adalimumab (anti-TNF-alpha) Adalimumab Beta D2E7 Humira Immunoglobulin G1, anti-(human tumor necrosis factor) (human monoclonal D2E7 heavy chain), disulfide with human monoclonal D2E7 light chain, dimer LU200134 Unii-fys6T7F842

1.3 CAS No.: 331731-18-1

1.4 CID: 107706

1.5 EINECS(EC#): 604-279-5

1.6 Molecular Formula: C6428H9912N1694O1987S46 (isomer)

1.7 Inchi: InChI=1S/C20H22N2O7S/c1-20(2,3)19(26)29-13-8-10-14(11-9-13)30(27,28)22-16-7-5-4-6-15(16)18(25)21-12-17(23)24/h4-11,22H,12H2,1-3H3,(H,21,25)(H,23,24)

1.8 InChkey: BTGNGJJLZOIYID-UHFFFAOYSA-N

1.9 Canonical Smiles: CC(C)(C)C(=O)OC1=CC=C(C=C1)S(=O)(=O)NC1=CC=CC=C1C(=O)NCC(O)=O

1.10 Isomers Smiles: CC(C(OC1C=CC(S(=O)(=O)NC2C(C(O)=NCC(O)=O)=CC=CC=2)=CC=1)=O)(C)C

2. Properties

2.1 Density: 1.4±0.1 g/cm3 (Predicted)

2.1 Refractive index: 1.598 (Predicted)

2.1 logP: 2.96 (Predicted)

3. Use and Manufacturing

3.1 GHS Classification: Signal: Warning
GHS Hazard Statements
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

H373 (100%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Precautionary Statement Codes
P260, P314, and P501

3.2 Methods of Manufacturing: Adalimumab is produced by recombinant DNA technology in a mammalian cell expression system and is purified by a process that includes specific viral inactivation and removal steps.

3.3 Usage: Treatment of rheumatoid arthritis and other chronic inflammatory diseases (monoclonal antibody).

4. Other Information

4.0 Uses: Treatment of rheumatoid arthritis and other chronic inflammatory diseases (monoclonal antibody).

4.1 Target: Value

4.2 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 K_d 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.

4.3 Originator: Cambridge antibody technology (US)

4.4 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.

4.5 Brand name: Humira

4.6 Pharmacology: Adalimumab is a fully human, anti-TNF-α IgG1 monoclonal antibody, which blocks the interaction of TNF-α with p55 and p75 cell surface receptors.
Adalimumab is typically administered as a 20-or 40-mg dose via subcutaneous injection either weekly or every other week. The subcutaneous route of administration may be favorable to infliximab, which requires an intravenous infusion.
The terminal half-life of adalimumab ranges from 15 to 19 days and early phase I trials demonstrated no significant pharmacokinetic advantage to weight-based dosing strategies.

4.7 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.

4.8 Side effects: Injection site reactions appear to be the most commonly reported adverse event and occur in up to 10% of patients treated. In an efficacy and safety study of adalimumab for ankylosing spondylitis, the number of adverse events was higher in patients receiving subcutaneous adalimumab 40 every other week than in those receiving placebo. The percentage of patients who experienced infectious complications was higher in the patients receiving adalimumab, but this finding was not statistically significant. No occurrences of latent tuberculosis reactivation, lupus-like syndromes, congestive heart failure, or secondary malignancies were reported.In a postmarketing surveillance study of RA patients, Schiff et al.reported that adalimumab appeared to be relatively safe and well tolerated. In their study, safety data from randomized clinical trials, open-label extensions, phase IIIb trials, and postmarketing reporting of adverse events in the USA were collected. Reported adverse events included serious infections (5.1 events/100 patient-years (PYs)), lymphoma (0.12/100 PYs), tuberculosis (0.27/100 PYs), opportunistic infections (0.08 events/100 PYs), demyelinating diseases (0.08/100 PYs), systemic lupus erythematosis/lupus-like syndrome (0.10/100 PYs), and congestive heart failure (0.28/100 PYs). The incidence of lymphoma did not appear to be significantly higher in patients treated with adalimumab than in RA patients who were na?ve to anti-TNF-α therapy; however, the rate of lymphoma may be higher in RA patients compared to the general population, particularly in patients with severe RA. Adverse events reported in patients with ophthalmic inflammatory disease treated with adalimumab have included injection site reactions, herpes simplex keratitis, and elevation of liver enzymes requiring cessation of therapy.

4.9 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.

4.10 Metabolism: Most likely removed by opsonisation via the reticuloendothelial system.

4.11 Precautions: Adalimumab is contraindicated in patients with known hypersensitivity to the medication or any of its components and in patients at risk for sepsis. In addition, the medication should be avoided in patients with a history of multiple sclerosis, active infection, or malignancy.

5. Computational chemical data

Molecular Weight: 434.46288g/mol
Molecular Formula: C₆₄₂₈H₉₉₁₂N₁₆₉₄O₁₉₈₇S₄₆
Compound Is Canonicalized: True
XLogP3-AA: 3
Exact Mass: 434.11477222
Monoisotopic Mass: 434.11477222
Complexity: 731
Rotatable Bond Count: 9
Hydrogen Bond Donor Count: 3
Hydrogen Bond Acceptor Count: 8
Topological Polar Surface Area: 147
Heavy Atom Count: 30
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADceB7OABAAAAAAAAAAAAAAAAAAAAAAAAwYAAAAAAAAAABQAAAHgQQSAAADgzB2AQyz4LABgKIAiXSWHDCCBAkIgAIiJmObMgOJjqE9buGO6jk1hGY6ceYyACOAIAAAAACAAABAAAAAAQAAAAAAAAAAA==