Organometallic Ligands

Octapeptide analog of Somatostatin; inhibits insulin and growth hormones

Carbimazole is an imidazole antithyroid agent that is used to treat hyperthyroidism. It reduces the production of diiodotyrosine and thyroxine, as well as the uptake and concentration of inorganic iodine by the thyroid. Once it has been converted to methimazole, the thyroid peroxidase enzyme is inhibited from coupling and iodinating the tyrosine residues on thyroglobulin therefore lowering the production of the thyroid hormones T3 and T4.

Non-prostanoid IP receptor agonist

Aprepitant is a neurokinin-1 receptor antagonist. It is an antiemetic which suppresses nausea and vomiting and has proven to be especially useful alongside cancer chemotherapy and as a tool in cancer-related studies. Aprepitant binds to the neurokinin-1 receptor in the brain, preventing it from binding to substance P. This prevents substance P from stimulating nerves in the vomiting center of the brain, reducing feelings of nausea and vomiting. Aprepitant has been shown to be effective against HIV infection, with no major side effects. The use of aprepitant for HIV therapy may be limited due to its ability to cause serious liver damage when taken with other drugs that are metabolized by cytochrome P450 enzymes.

HMG-CoA reductase inhibitor

Inhibits proteosomes of class peptide epoxyketone; antineoplastic

Inhibitor of BET bromodomain; antineoplastic

Abiraterone is an anti-cancer drug that has been shown to be effective in treating prostate cancer. It works by blocking the production of testosterone by inhibiting androgen synthesis. Abiraterone does this by inhibiting CYP17A1, which converts cholesterol into pregnenolone, and then into progesterone and testosterone. Furthermore, it binds to the enzyme steroid 5-alpha reductase, which converts testosterone into dihydrotestosterone (DHT). Abiraterone is usually a last resort for patients who have stopped responding to other lines of hormone therapies, which is known as second-line therapy.

17-AAG is the first clinically tested hsp90 inhibitor that exhibits antitumor activity. Its antitumor effects are documented in vivo for various animal models, including erbB2-dependent breast cancer, prostate cancer models, and melanoma.

Activator of p53; inhibitor of NF-?B

CFTR modulator

Minoxidil is an antihypertensive agent used for the treatment of resistant hypertension that has caused organ damage. This drug has vasodilatory properties and promotes the survival of human dermal papillary cells. Therefore, this drug is also used to treat alopecia.

Thromboxane A2 synthetase inhibitor

A2A adenosine receptor antagonist

Platelet activating factor (PAF) inhibitor

ATP-competitive inhibitor of Met and VEGFR2

Adenosine-A2A receptor agonist

Inhibitor of histone deacetylases

Inhibitor of mutant B-rafV600E protein that results in decreased proliferation of cancer cells with this mutation. Treatment of metastatic melanoma in patients harboring the V600E mutation, had improved disease outcome. This antitumor activity is enhanced when combined with MEK inhibitor trametinib.

GSK-126 is a potent inhibitor of histone lysine methyl transferase 2, which is encoded by the enhancer of zeste homolog 2 gene (EZH2). The EZH2 protein regulates cell cycle as it represses the Polycomb-Repressive Complex 2 (PRC2), allowing cells to divide actively. GSK-126 inhibits the EZH2 by targeting the catalytic domain (SET) of the enzyme and therefore blocks the PCR2 repression mechanism, resulting in cell proliferation arrest. The compound has shown therapeutic potential for a variety of cancers.