Atypical drugs Flashcards
Uses and examples of Tubulin inhibitors
They treat certain cancers and gout.
E.g., vinblastine, vincristine, eribulin, and colchicine.
They target beta-tubulin in microtubule formation, to inhibit mitosis.
Cereblon inhibitors uses and example
Treat multiple myeloma.
They bind to cereblon, a nuclear protein that is part of an E3 ubiquitin ligase complex. Cereblon binds ubiquitin to lysine residues, particularly on transcription factors. Promotes proteasome-mediated degradation.
E.g., thalidomide.
Accelarates the degradation of the target proteins in multiple myeloma.
examples of Drugs with unknown MoA
Cannabidiol, sodium valproate, latanoprost, etc…
Vaccines (biopharmaceutical) mechanism of action
inactivated microbes, toxins and surface proteins that stimulate an immune response to provide protection.
Recombinant proteins (biopharmaceuticals) examples and what they treat
e.g., insulin growth hormone, etc…
Recombinant enzymes such as DNAse, glycosides, proteinases
Conestat alfa is a naturally occurring proteinase inhibitor.
Idursulfase is a recombinant enzyme used to treat hunter syndrome, by removing the build up of sulphate compounds associated with hunter syndrome.
Antibody overview and role endogenously, and for monoclonal antibodies.
Endogenously produced by B lymphocytes in response to antigens expressed by pathogens, elemental metals and foreign proteins.
Polyclonal antibodies made from multiple immune cells, and will express several antibody types.
Monoclonal antibodies generated from single immune cell: Only one antibody type produced.
The antibodies interact with natural killer T cells to release cytokines, macrophages and mast cells to trigger phagocytosis, and neutrophils to trigger phagocytosis and degranulation
Monoclonal antibodies therapeutic exploitation
Treats non-hodgkins lymphoma, colorectal cancer, head/neck cancer, and breast cancer.
Also treats inflammatory conditions such as arthritis, MS, psoriasis, hypercholesterolemia, and lupus.
Advantages: high affinity and selectivity. targets hard to treat diseases, and high half-life: infrequent dosing.
Limitations: cost, poor tissue penetration, only for EC targets, and high half life can be a limitation if adverse effects occur.
Antibody and drug conjugate example
Trastuzumab emtansine combines a monoclonal antibody and a tubulin inhibitor to treat HER2/EGFR-positive breast cancer.
emtansine is cytotoxic to the breast cancer cells and inhibits the proliferation of the cancerous cells.
drug classes to Target nucleic acids
Downregulates mRNA by antisense oligonucleotides (ASODNs) or siRNA.
ASODNs examples and mechanisms
Nusinersen is an ASODN to treat SMN1 loss-of-function mediated spinal muscular atrophy. It targets SMN2 and changes the protein encoding to more closely resemble SMN1.
Inotersen binds to mRNA, to slow the translation of transthyretin protein, which mutated forms are associated with hereditary transthyretin amyloidosis.
Volanesorsen slows the translation of apolipoprotein C-III, to treat familial chrlomicronemia syndrome, which is associated with high [triglycerides], due to high function of apolipoprotein C-III.
Ataluren suppresses the nonsense mutation of dystrophin that is associated with duchenne muscular dystrophy. This mutation prevents the correct translation of dystrophin. Ataluren allows the full encoding of the protein.
Small interfering RNA (siRNA) exploitation example and mechanism
Patisiran treats transthyretin amyloidosis. It targets a conserved region of both mutant and WT of the transthyretin gene, and interferes in the translation of the protein. Reduction in [transthyretin] treats the disease.
