Genomics Drugs for Final

zynteglo

• ex vivo

• for β thalassemia

• has thr-87-glu switch

• myeloablative before infusion

luxturna

• RPE65 gene mutations that cause vision deterioration

• one time therapy

• vector is adeno-associated virus of serotype 2

• in vivo

Zolgensma

• for SMA

• AAV9 virus is vector

• has SMN cDNA

• in vivo

CAR-T cell therapy

kymriah, yescarta, tecartus

• t cells that are harvested from blood, modified, reintroduced to attack cancer

eteplirsen

• blocks message of siRNA

• mopholino ASO group

• binds to dystrophin primary transcript

• exon 51 spliced out

Onpatro (patisiran)

• binds to TTR mRNA, makes complex

• complex recognized by RISC

• RISC degrades, prevents translation

• siRNA

Spinraza (nusinersen)

• modifcations

  • base has 2-O-2 methoxyethyl nucleoside

  • phosphate replaced with thioate

• binds to SMN2 and prevents exon 7 from being spliced

Certolizumab

• TNF-⍺ drug

• 2 PEG groups attached to C terminus

• Fc region removal reduces ADCC

Antibody dependent cell mediated cytotoxicity (ADCC)

• mAb binds to tumor antigen

• NK cells recognized Fc region via Fc 𝛾 receptors

  • IgG1 mAb = proinflammatory effector functions

• NK cells cause tumor cell lysis

Zaltrap

• soluble VEGF receptor fused to antibody Fc region

• trap to prevent VEGF ligands from binding to VEGF receptor

• produced via alternative splicing

  • cDNA for receptor shortened to exclude DNA for membrane part of VEGF

Trastuzumab

• mAB that binds to HER2 only

• only used in HER2 breast cancer

Pertuzumab

• target dimerization domain of HER2

• blocks ligand dependent heterodimerization of HER2

• Targets a different epitope of HER2

Kadcyla

• covalent MCC linker that connects drug DM1 to lysines in the Fc region

• antibody degradation releases DM1 which then inhibits mitosis

Lumizyme

• for Pompe’s disease

• infused over 4 hours

• BBW for hypersensitivity, cardiorespiratory failure, infusion reaction

Nexviazyme

allow vials to reach room temperature prior to reconstitution

look for discoloration or particles in solution

Novolog

• 2nd generation insulin

• aspartate replaces proline at position 28B

  • makes it rapid acting

Lantus

• 2nd generation insulin

• glycine replaces asparagine at 21A

• two extra arginine added to B chain

  • slower acting due to decreased solubility

Epoetin Alfa

• used for treatment of anemia due to chronic renal failure

Filgrastim, Pegfilgrastim

• Colony stimulating factor

• glycoprotein that stimulates bone marrow to produce and release granulocytes into the bloodstream

• 1st is dosed daily, second is every chemo cycle

Algucosidase alpha (myozyme)

• recombinant human ⍺-1,4 glucosidase

• CHO cells used here have sugar cells that are not mannose

• glycoprotein treated to remove sugars, expose mannon

• inefficient uptake here

• Pompe

Nexviazyme

• Produced in CHO cells

• recombinant human ⍺-1,4 glucosidase enzyme

• cojugated with multiple synthetic bis-mannose-6-phosphate-tetra-mannose glycans

• POST production glycoengineering

• designed to improve cellular enzyme uptake

Pombiliti

• recombinant human a-1,4 glucosidase enzyme derived from CHO cells

  • using perfusion methodology, resulting in cho derived n-glycans

  • CHO cells engineered with golgi-mannosidase —> high density mannose phosphate produced

• another post-translational glycoengineering

Miglustat (opfolda)

• used in combo with Pombiliti

• helps protein stay folded

• N-alkylated iminosugar

  • synthetic D-glucose analog

• dissociates from pombiliti after complex internalized

prevents initiation by blocking the RNA/DNA polymerase hybrid which eliminated TB

• if he uses manitin as distractor, do not pick

streptomycin

inhibit initiation and cause mRNA misread

tetracycline

bind to 30s subunit and inhibits the binding of aminoacyl-tRNA

Chloramphenicol

inhibits the peptidyl transferase activity of the 50s ribosomal subunit

erythromycin

binds to 50s subunit and inhibits translocation

cisplatin

DNA intrastrand cross linking

BRAC analysis

• testing diagnostic used to identify germline mutations in BRCA1, BRCA2

• important for determining patient’s eligibility for therapies like PARP inhibitors

Sulfasalazine

• remains inactive until it reaches gut, where azoreductase encoded by the gut microbiome cleave the N-N double bond to release active 5-ASA

• AKA need gut microbiome to activated sulfasalazine; therefore we are taking an antibiotic we can’t conver sulfasalazine

sorivudine

5-FU metabolism enzyme (DPD) is blocked by _____ metabolite (BVU) causing a toxic 5-FU buildup