enzymes are powerful biological catalysts that are essential for the proper maintenance and propagation of any organism. these properties make them excellent candidates as therapeutic targets to combat diseases of either genetic or pathogenic origin. in this regard, one goal of molecular medicine is to develop and implement effective agents that can modulate the activity of various enzymes involved in essential biological pathways. the process of developing and characterizing these small molecules, i.e., rational drug design, often requires a priori knowledge of the enzyme in question....
There continues to be an explosion of research on issues
of pharmacologic relevance to primary eye care delivery.
New ophthalmic formulations are being developed, new
diagnostic methods introduced,and new medications and
delivery systems are available that were unheard of a
decade ago. It is important that these new concepts be
introduced to students and practitioners alike.
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Kinetic modeling of tricarboxylic acid cycle and glyoxylate bypass in Mycobacterium tuberculosis, and its application to assessment of drug targets
Adequate aqueous solubility of new chemical entities (NCEs) is one of the key
properties required for successful pharmaceutical formulation development.
Solubility is generally defi ned as the concentration of the compound in a solution
which is in contact with an excess amount of the solid compound when the concentration
and the solid form do not change over time (Sugano et al. 2007 ) .
Many protein substrates of caspases are cleaved at noncanonical sites in
comparison to the recognition motifs reported for the three caspase sub-groups. To provide insight into the specificity and aid in the design of
drugs to control cell death, crystal structures of caspase-7 were determined
in complexes with six peptide analogs (Ac-DMQD-Cho, Ac-DQMD-Cho,
Ac-DNLD-Cho, Ac-IEPD-Cho, Ac-ESMD-Cho, Ac-WEHD-Cho) that
span the major recognition motifs of the three subgroups.
Liver microsomal preparations are routinely used to predict
drug interactions that can occurin vivo as a result of inhi-bition of cytochrome P450 (CYP)-mediated metabolism.
However, the concentration of free drug (substrate and
inhibitor)at its intrahepatic site of action, a variable that
cannot be directly measured, may be significantly different
from that in microsomal incubation systems.
The structural and kinetic effects of amprenavir (APV), a clinical HIV pro-tease (PR) inhibitor, were analyzed with wild-type enzyme and mutants
with single substitutions of V32I, I50V, I54V, I54M, I84V and L90M that
are common in drug resistance. Crystal structures of the APV complexes at
resolutions of 1.02–1.85 A
reveal the structural changes due to the muta-tions.
p38 Mitogen-activated protein kinase alpha (p38 MAPKa) is a member of
the MAPK family. It is activated by cellular stresses and has a number
of cellular substrates whose coordinated regulation mediates inflammatory
responses. In addition, it is a useful anti-inflammatory drug target that has
a high specificity for Ser-Pro or Thr-Pro motifs in proteins and contains a
number of transcription factors as well as protein kinases in its catalog
of known substrates.
(t1/2) and the apparent volume of distribution Vapp (p. 28) by the equation: Vapp t1/2 = In 2 x –––– Cltot The smaller the volume of distribution or the larger the total clearance, the shorter is the half-life. In the case of drugs renally eliminated in unchanged form, the half-life of elimination can be calculated from the cumulative excretion in urine; the final total amount eliminated corresponds to the amount absorbed.
Cancer Cell Biology The treatment of most human cancers with conventional cytoreductive agents has been unsuccessful due to the Gompertzian-like growth kinetics of solid tumors (i.e., tumor growth is exponential in small tumors, with increasing doubling times as tumors expand; since conventional chemotherapeutic agents target proliferating cells, noncycling cells in large tumors are relatively resistant). Genetic instability is inherent in most cancer cells and predisposes to the development of intrinsic and acquired drug resistance. Thus, although tumors arise from a single cell (i.e.
Highly active, small-molecule furin inhibitors are attractive drug candidates
to fend off bacterial exotoxins and viral infection. Based on the 22-residue,
active Lys fragment of the mung bean trypsin inhibitor, a series of furin
inhibitors were designed and synthesized, and their inhibitory activity
towards furin and kexin was evaluated using enzyme kinetic analysis.