Med Chem - Psoriasis Biologics Flashcards
name 5 biologics for psoriasis
alefacept
efalizumab
ixekizumab
ustekinumab
deucravacitinib
alefacept MOA
fusion protein that binds CD2 on T cells, preventing T cell activation
how is alefacept administered?
IM injections
efalizumab MOA
monoclonal antibody
targets LFA1 on T cells (lymphocyte function associated antigen), blocking T cell from binding to iCAM1 (intracellular adhesion molecule
how is efalizumab administered
subq injections
Ixekizumab MOA
monoclonal antibody that binds IL-17a cytokine, preventing it from binding to the IL-17a receptor on the T cell surface — inhibits inflammation
ixekizumab is indicated for….
moderate-severe plaque psoriasis
which monoclonal antibody used in psoriasis is a fully human mab?
ustekinumab (stelara)
explain the MOA of ustekinumab
binds the p40 subunit of 2 CYTOKINES - IL-12 and IL-23!! blocks BOTH from binding to their receptors and causing T cell activation
how is ustekinumab given?
what is it indicated for?
both plaque and psoriatic arthritis
given as SUBQ injections
if something has the prefix “Ar” what does this mean about it’s chemistry
(r)
if something has pure “s” stereochemistry what might its prefix be
Es
what is deucravacitinib indicated for
plaque psoriasis
what does TYK2 stand for
tyrosine kinase 2 enzyme
belongs to JAK kinase family
why is deucravacitinib deuterated
gives it HIGH SELECTIVITY for allosteric inhibition of TYK2
TYK2 inhibition by deucravacitinib leads to what?
blocking IL-12 and IL-23 signaling
explain the mechanism of action of deucravacitinib
TYK2 has 2 components - a regulatory domain with an allosteric site and a catalytic domain with an active site
deucravactinib has high selectivity for the allosteric site on the regulatory domain of TYK2
binding here causes a conformational change in the active site of TYK2 in the catalytic domain. this conformational change makes ATP no longer able to bind to the active site of TYK2 — preventing the action of the enzyme
leads to blockade of IL-12 and IL-23 signaling
explain the difference between JAK1-3 inhibitors and TYK2 inhibitor (deucravacitinib) as far as the site that they bind
traditional JAK1-3 inhibitors bind the active site of TYK2 on the catalytic portion
deucravacitinib, however, binds the allosteric site on the regulatory domain, changing the configuration of the active site on the catalytic domain and preventing ATP from binding
