INN name :

TASOCITINIB
USAN name:

Tofacitinib, TASOCITINIB
CODE DESIGNATION :
CP-690550

CHEMICAL NAMES:

3-{(3R, 4R)-4-methyl-3-[methyl (7H-pyrrolo[2,3d] pyrimidin-4-yl)amino]piperidin1-yl}-3- oxo-propanenitrile 1-PIPERIDINE PROPANE NITRILE, 4-METHYL-3-(METHYL-7H-PYRROLO(2,3D)PYRIMIDIN-4-YLAMINO)-.BETA.-OXO-, (3R,4R)3-PIPERIDINAMINE, 1-(CYANOACETYL)-4-METHYL-N-METHYL-N-1H-PYRROLO (2,3-D)PYRIMIDIN-4-YL-, (3R,4R)Under supervision of Prof. M.A.Eldawy made by student: Michael William

CAS registry number (Chemical Abstracts Service):

477600-75-2

Innovative company &country:

Pfizer
Chemical structure :

Using chemsketch software Identifiers Class (ATC coding system): not available PubChem: CID 9926791 UNII :87LA6FU830 Synonyms :CP-690550
Under supervision of Prof. M.A.Eldawy made by student: Michael William

Peak projections: $2.6 billion (Credit Suisse) Chemical data: MOLECULAR WEIGHT:
312.369 g/mol

empirical formula is:

C16H20N6O

SMILES: emolecule: N#CCC(=O)N1CC[C@@H](C)C(C1)N(C)c1ncnc2[nH]ccc12 Pubmed: Isomeric SMILES: C[C@@H]1CCN(C[C@@H]1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N

Canonical SMILES : CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N

InChI: InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-2016/h4,7,10- 11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-13+/m1/s1

InChIKey: UJLAWZDWDVHWOW-YPMHNXCESA-N
Under supervision of Prof. M.A.Eldawy made by student: Michael William

Indication:

treatment of rheumatoid arthritis (RA), psoriasis, inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection.
Routes: Oral, topical Half-life : 25 hours

Mode of action :

The Basics of JAK/STAT Signaling

There are 3 principal components:
123-

a receptor(cytokine receptors.) a member of the Janus kinase (JAK) family, a member of the signal transducer and activator of transcription (STAT) family (transcription factors)

Once activated, the JAKs phosphorylate the STATs, when phosphorylated they move from cytoplasm into the nucleus where they bind to specific DNA sequences and drive or inhibit the suppression of target genes

Under supervision of Prof. M.A.Eldawy made by student: Michael William

tofacitinib is an inhibitor of the enzyme Janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway that transmits information outside the cell into the cell nucleus, influencing DNA transcription. Improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1dependent genes in joint tissue
Under supervision of Prof. M.A.Eldawy made by student: Michael William

pharmacophoric group :

Under supervision of Prof. M.A.Eldawy made by student: Michael William

Drawn by student Michael William using molegro virtual docking software

Under supervision of Prof. M.A.Eldawy made by student: Michael William

Drawn by student Michael William using molegro virtual docking software

Under supervision of Prof. M.A.Eldawy made by student: Michael William

Binding interaction : Hydrogen bond between glutamic acid 930 and hydrogen of 7H of pyrolopyrimidine Hydrogen bond between the hydrogen of leucine and N1 of pyrolopyrimidine Electrostatic interaction between cyanide gp and valine amino acid piperidine ,methyl,pyrolopyrimidine and leucine983,leucine855,alanine880
Under supervision of Prof. M.A.Eldawy made by student: Michael William

STRUCTURES, GENERIC NAMES, INNOVATOR BRAND NAMES OF RELATED DRUG : Methotrexate

CHEMICAL NAMES: (2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}benzoyl)amino]pentanedioic acid empirical Formula: C20H22N8O

Mol. mass: 454.44 g/mol

CAS REGISTRY NUMBER : 59-05-2

Under supervision of Prof. M.A.Eldawy made by student: Michael William

Disadvantage of methotrexate:

Not specific for the treatment of rheumatoid arthritis. (Gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis. bone marrow suppression and gastrointestinal toxicity Mechamism of action: inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known. Advantages of Tofacitinib over methotrexate: 1- More specific for treatment of rheumatoid arthritis 2- Show high safety profile in clinical trials(long-term safety record is favorable) 3- tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue 4- Tofacitinib - an oral Janus kinase inhibitor - when used in combination with methotrexate can produce significant improvements in patients with rheumatoid arthritis who have had an inadequate response to tumor necrosis factor (TNF) inhibitors. 5- orally administered treatment option for patients with an inadequate or toxic response to conventional DMARDs.

Under supervision of Prof. M.A.Eldawy made by student: Michael William

Disadvantages of Tofacitinib: increased blood cholesterol levels neutropenia In 14 October 2011 : There was one death in the 10-m pulmonary emboli - but this was judged not to be due to the study medication, Burmester said. The -year-old obese woman who had hypertension.

Under supervision of Prof. M.A.Eldawy made by student: Michael William