Med Chem - Psoriasis Biologics

Question 1

name 5 biologics for psoriasis

Answer 1

alefacept
efalizumab
ixekizumab
ustekinumab
deucravacitinib

Question 2

alefacept MOA

Answer 2

fusion protein that binds CD2 on T cells, preventing T cell activation

Question 3

how is alefacept administered?

Answer 3

IM injections

Question 4

efalizumab MOA

Answer 4

monoclonal antibody

targets LFA1 on T cells (lymphocyte function associated antigen), blocking T cell from binding to iCAM1 (intracellular adhesion molecule

Question 5

how is efalizumab administered

Answer 5

subq injections

Question 6

Ixekizumab MOA

Answer 6

monoclonal antibody that binds IL-17a cytokine, preventing it from binding to the IL-17a receptor on the T cell surface — inhibits inflammation

Question 7

ixekizumab is indicated for….

Answer 7

moderate-severe plaque psoriasis

Question 8

which monoclonal antibody used in psoriasis is a fully human mab?

Answer 8

ustekinumab (stelara)

Question 9

explain the MOA of ustekinumab

Answer 9

binds the p40 subunit of 2 CYTOKINES - IL-12 and IL-23!! blocks BOTH from binding to their receptors and causing T cell activation

Question 10

how is ustekinumab given?
what is it indicated for?

Answer 10

both plaque and psoriatic arthritis

given as SUBQ injections

Question 11

if something has the prefix “Ar” what does this mean about it’s chemistry

Answer 11

(r)

Question 12

if something has pure “s” stereochemistry what might its prefix be

Answer 12

Es

Question 13

what is deucravacitinib indicated for

Answer 13

plaque psoriasis

Question 14

what does TYK2 stand for

Answer 14

tyrosine kinase 2 enzyme

belongs to JAK kinase family

Question 15

why is deucravacitinib deuterated

Answer 15

gives it HIGH SELECTIVITY for allosteric inhibition of TYK2

Question 16

TYK2 inhibition by deucravacitinib leads to what?

Answer 16

blocking IL-12 and IL-23 signaling

Question 17

explain the mechanism of action of deucravacitinib

Answer 17

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

Question 18

explain the difference between JAK1-3 inhibitors and TYK2 inhibitor (deucravacitinib) as far as the site that they bind

Answer 18

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