biochem final hell drugs

acyclovir

treat herpes simplex, inhibits viral DNA polymerase by chain termination

daunorubicin, doxorubicin (adriamycin)

“red devil” natural products used to treat cancer

4 rings, 3 aromatic flat plane shape

intercalates with DNA (slips between bases)

interferes with topoisomerase

bleomycin

natural product used to treat squamous cell carcinoma, lymphoma, head and neck tumors, and testicular cancer

halts replication by breaking up DNA with radicals

nitrogen mustard (mustargen)

use to treat cancer

primary alkyl halide is good leaving group

alkylating agent alkylates DNA at N-7 guanine and cross-link DNA

cyclophosphamide (cytoxan)

used to treat lymphomas, leukemias, multiple myeloma, neuro-and retinoblastoma, breast and ovarian cancer

alkylating drug

cisplatin

used to treat cancer, binds primarily to guanine bases in DNA strands, stopping DNA from unzipping and replicating, stopping cancer growth and causing cell death

crosslinks both inter and intrastrand

Rifampin (rifampicin)

antibiotic, inhibits bacterial RNA polymerase, binds to RNA polymerase and changes its conformation so it cannot initiate RNA synthesis

RNA polymerase does not bind rifampin, RNA synthesis is unaffected

primarily used to treat tuberculosis and leprosy

actinomycin D (dactinomycin)

used to treat Wilm’s tumor, rare form of kidney cancer

originally antibacterial agent

first chemotherapy for solid tumor

inhibits DNA replication and transcription by intercalating between bases in DNA double helix

3 flat aromatic rings

alpha-Amantin

produced by mushroom, binds to DNA polymerase II, blocking elongation, causes coma and death

puromycin

antibiotic, inhibits both prokaryotic and eukaryotic translation

mimics tyrosyl-tRNA

instead of ester bond it makes amide bonds (more stable)

-binds to A site, kicks amino acid off tRNA, terminates translation

tetracycline (doxycycline)

binds to small subunit of ribosome, prevents aminoacyl-tRNA from binding to A site

also EF-Tu hydrolyzes GTP causing bacterial site to waste energy

erythromycin, zithromax, clindamycin

binds to 50S subunit, inhibits translocation

linezolid (zyvox)

also binds to 50S subunit

neomycin (neosporin), gentamicin

aminoglycoside, binds to small subunit of ribosome, causes mistranslation

protonated amino groups bind to anionic 16S rRNA on 30S subunit (A site)

tobramycin

aminoglycoside, treat eye infections

mupirocin (bactroban)

inhibits bacterial ILE-tRNA synthetase, binds in active site

small Kd

Ricin

N-glycosidase from castor oil, removes adenine base of conserved nucleotide of 28S subunit of eukaryotic ribosome, can’t bind elongation factors

diptheria toxin

enzyme catalyzing:

eukaryotic elongation factor 2 (eEF-2) ADP-ribosylation, inhibiting translocation, death

androstendione, dianabol

anabolic steroids (androgen receptor), analogs of testosterone

agonist (increase in gene expression)

tamoxifen

estrogen receptor, antagonist

synthetic analog of estrogen that blocks binding of coactivators by producing conformational change in estrogen receptor

decreases transcription of genes regulated by estrogen, resulting in reducing growth of breast cancer cells

tamoxifen makes helix 12 change conformation, bloacking coactivator site binding, no transcription

Fulvestrant (Faslodex)

binds to estrogen receptor, blocking binding of estradiol and preventing dimerization of ER

Er monomer is degraded via ubiquitin-proteosome pathway

Leqvio (Inclisiran)

a small interfering RNA that targets PCSK9 mRNA, leading to decreased levels of LDL cholesterol in the blood

treat individuals with heterozygous familial hypercholesterolemia

Augmentin

antibiotic, penicillin derivative amoxicillin + clavulanic acid

or ampicillin + sulbactam

humalog

insulin lispro, recombinant analog of insulin

switch proline and lysine with site-directed mutagenesis

peaks faster than insulin

aspirin

inhibits cyclooxygenase (COX) enzymes, preventing production of thromboxane

inhibits activation of platelets

Xarelto (Rivaroxaban), Savaysa (Edoxaban), Eliquis (Apixaban)

inhibit Factor Xa, preventing thrombin formation and reducing blood clotting

reversible noncompetitive inhibition

low Kd

antidote factor X but serine protease mutated to alanine

Argatroban, Pradaxa

direct thrombin inhibitors used to prevent blood clots

reversible noncompetitive inhibtion

Lipirudin

alternative to heparin, recombinant form of leech hirudinthat directly inhibits thrombin, preventing clot formation.

bivalirudin is synthetic congener of hirudin

Alteplase (WT tPA), Tenecteplase (TNKase), Reteplase

are thrombolytic agents that promote the breakdown of fibrin in blood clots, enhancing clot dissolution.

produced via recombinant DNA

TNKase uses site directed mutagenesis to increase kcat/km

treat conditions caused by formation of spontaneous thrombi that can lead of myocardial infarction and thrombolytic stroke