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DARPins (designed ankyrin repeat proteins) are a novel class of binding molecules with the potential to overcome limitations of monoclonal antibodies, hence allowing novel therapeutic approaches. DARPins are small, single domain proteins (14 kDa) which can be selected to bind any given target protein with high affinity and specificity. These characteristics make them ideal agonistic, antagonistic or inhibitory drug candidates. Furthermore, DARPins can be engineered to carry various effector functions or combine multiple binding specificities, enabling completely new drug formats. Taken together, DARPins are a prominent member of the next generation of protein therapeutics with the potential to surpass existing antibody drugs. For details visit http://www.drugdiscoverytoday.com/echoice/feb2009/Stumpp.pdf Cortesy Dr. Tariq Salman Subscribe to Drugs Information Center by Email

ZEFTERA the only approved antibiotic in its class (cephalosporin) by Health Canada to demonstrate efficacy against Methicillin-resistant Staphylococcus aureus (MRSA), a growing public health concern in both hospital and community settings.ZEFTERA is specially designed to tightly bind to and inhibit targets in both gram-positive (including MRSA) and gram-negative bacteria. The approval of ZEFTERA for the treatment of complicated skin and skin structure infections, including non-limb threatening diabetic foot infections without concomitant osteomyelitis, was based on results of two Phase III, double-blind, randomized, multi-centre, global trials involving 817 patients with cSSSI 2,3. The second Phase III trial included patients with non-limb threatening diabetic foot infections (mild, moderate or severe)3. Pathogens identified at baseline in this subpopulation included MSSA (38 per cent), MRSA (13 per cent), E. cloacae (9 per cent), and P.mirabilis (7 per cent). The results demonstrat...

Integrase is a viral enzyme that is essential for HIV type 1 (HIV-1) replication; it catalyzes the insertion of proviral DNA into the host-cell genome. Raltegravir is an integrase inhibitor and specifically inhibits proviral DNA-strand transfer, with potent in vitro activity against HIV-1. In most patients with highly drug-resistant HIV, the resistance develops because of sequential exposure to HIV drugs in the context of incomplete virologic suppression. The genetic barrier to drug resistance for several of the most important HIV agents is low, requiring only a single point mutation to confer loss of activity. Drug-resistant virus can also be transmitted from person to person, although the transmission of strains resistant to multiple classes of drugs is rare. Subscribe to Drugs Information Center by Email

Major classes of agents employed in immunosuppressive therapy: Corticosteroids Cytotoxic Agents T-cell suppressive agents Antibodies Mechanism of action: Cytotoxic Agents- suppress bone marrow function 1. Cyclophosphamide: a. Primarily suppresses B-cell production; lowers humoral immunity b. Used to treat severe rheumatoid arthritis c. Not normally used for graft rejection 2. Azathioprine a. Primarily suppresses T-cell production b. Used for graft rejection c. Normally used in combination with corticosteroids 3. Mycophenolate Mofetil (CELLCEPT) a. Mechanism of action: inhibits inosine monophosphate dehydrogenase; an enzyme required for de novo purine synthesis b. Selective because T and B cells rely on de novo pathway c. Suppresses lymphocyte proliferation and B-cell antibody production d. Can be used to inhibit transplant rejection T-Cell Suppressor Agents 1. Cyclosporine and Tacrolimus a. Mechanism of action: block proliferative response of T-cells to antigen by inhibiting calcineuri...

Infliximab is a chimeric IgG 1K monoclonal antibody. Its approximate molecular weight is 149,100 daltons. It is composed of human constant and murine variable regions. Infliximab binds specifically to human TNF-α. Biological effects of infliximab TNF-α induces proinflammatory cytokines that include IL-1 and IL-6. These cytokines enhance leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, and induction of acute phase and other liver proteins. Infliximab neutralizes the biological activity of TNF-α by binding with high affinity to the soluble and transmembrane forms of TNF-α and inhibits binding of TNF-α with its receptors. A related cytokine that utilizes the same receptors as TNF-α, TNF-beta (lymphotoxin α) is not neutralized by infliximab. It has been found to downregulate IL-18 but not IL-12 and IL-13. It upregulates the expression of CX...