Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by injection into a vein, under the skin, or into the cerebrospinal fluid. There is a liposomal formulation for which there is tentative evidence of better outcomes in lymphoma involving the meninges.
Fluorouracil, sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream it is used for actinic keratosis, basal cell carcinoma, and skin warts.
The chiral pool is a "collection of abundant enantiopure building blocks provided by nature" used in synthesis. In other words, a chiral pool would be a large quantity of common organic enantiomers. Contributors to the chiral pool are amino acids, sugars, and terpenes. Their use improves the efficiency of total synthesis. Not only does the chiral pool contribute a premade carbon skeleton, their chirality is usually preserved in the remainder of the reaction sequence.
Arsenic trioxide is an inorganic compound with the formula As
2O
3. As an industrial chemical, its major uses include the manufacture of wood preservatives, pesticides, and glass. It is sold under the brand name Trisenox among others when used as a medication to treat a type of cancer known as acute promyelocytic leukemia. For this use it is given by injection into a vein.
Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. It is given by injection into a vein.
Podophyllotoxin (PPT) is the active ingredient in Podofilox, which is a medical cream that is used to treat genital warts and molluscum contagiosum. It is not recommended in HPV infections without external warts. It can be applied either by a healthcare provider or the person themselves.
Epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials, epothilones have better efficacy and milder adverse effects than taxanes.
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction.
Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells. Topoisomerase inhibitors influence these essential cellular processes. Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism. These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single- and double stranded DNA breaks they cause can lead to apoptosis and cell death. Because of this ability to induce apoptosis, topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells.
Polyketide synthases (PKSs) are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share striking similarities with fatty acid biosynthesis.
Ixabepilone is a pharmaceutical drug developed by Bristol-Myers Squibb as a chemotherapeutic medication for cancer.
A mitotic inhibitor, microtubule inhibitor, or tubulin inhibitor, is a drug that inhibits mitosis, or cell division, and is used in treating cancer, gout, and nail fungus. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow through continuous division that eventually spread through the body (metastasize). Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics, where they stop cell division at a stage where chromosomes can be easily examined.
Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of Camptotheca acuminata, a tree native to China used in traditional Chinese medicine. It has been used clinically more recently in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today: topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also been found in other plants including Chonemorpha fragrans.
Eribulin, sold under the brand name Halaven among others, is an anti-cancer medication used to treat breast cancer and liposarcoma.
Kosan Biosciences, Inc., was a pharmaceutical company which dealt with cancer therapeutics medications. The company was working on advancing two new classes of anticancer agents through clinical development: heat shock protein 90 (Hsp90) inhibitors and epothilones.
Omacetaxine mepesuccinate, formerly named as homoharringtonine or HHT, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML).
The Enders SAMP/RAMP hydrazone alkylation reaction is an asymmetric carbon-carbon bond formation reaction facilitated by pyrrolidine chiral auxiliaries. It was pioneered by E. J. Corey and Dieter Enders in 1976, and was further developed by Enders and his group. This method is usually a three-step sequence. The first step is to form the hydrazone between (S)-1-amino-2-methoxymethylpyrrolidine (SAMP) or (R)-1-amino-2-methoxymethylpyrrolidine (RAMP) and a ketone or aldehyde. Afterwards, the hydrazone is deprotonated by lithium diisopropylamide (LDA) to form an azaenolate, which reacts with alkyl halides or other suitable electrophiles to give alkylated hydrazone species with the simultaneous generation of a new chiral center. Finally, the alkylated ketone or aldehyde can be regenerated by ozonolysis or hydrolysis.
Ting-Chao Chou is a Chinese American theoretical biologist, pharmacologist, cancer researcher and inventor. His 353 scientific papers have been cited in 40,108 times in over 1,469 biomedical journals as of October 15, 2022. He derived the median-effect equation (MEE) from the physico-chemical principle of the mass-action law, and introduced the median-effect plot in 1976. With Paul Talalay of the Johns Hopkins University School of Medicine, he derived the combination index equation (CIE) for multiple drug effect interactions, and introduced the concept of combination index (CI) for quantitative definition of synergism (CI<1), additive effect (CI=1), and antagonism (CI>1) using computerized simulations. This article has received 7,731 citations internationally in a broad spectrum of journals. Since all terms of MEE and CIE are dimensionless relativity ratio thus generally applicable regardless in vitro, in animals and in clinical trials, or physical states, resulting in econo-green bioresearch and new drug evaluation and bio-development. This integrated theory and algorithms allow conducting small number of dose-data points, conservation of laboratory animals and reducing the number of patients in clinical trials. Consequently, this allows saving time and cost and resources as well as increasing efficiency and cost-effectiveness in medical, pharmaceutical research and new drug development with automated computer simulation. With colleagues, T.C. Chou is inventor/co-inventor of 40 U.S. Patents, mainly for anticancer agents. He was induced to Johns Hopkins Society of Scholars in 2019.
Triphenylethylene (TPE) is a simple aromatic hydrocarbon that possesses weak estrogenic activity. Its estrogenic effects were discovered in 1937. TPE was derived from structural modification of the more potent estrogen diethylstilbestrol, which is a member of the stilbestrol group of nonsteroidal estrogens.
Diverted total synthesis in chemistry is a strategy in drug discovery aiming at organic synthesis of natural product analogues rather than the natural product itself. The target can be the modification of a natural product or the modification of an intermediate. In this sense it differs from other strategies such as total synthesis and semisynthesis. The purpose can be gaining a scientific understanding of the biological activity of the original natural product or the discovery of new drugs with the same biological activity but simpler to produce. The concept was introduced by Samuel J. Danishefsky in 2006. Notable examples of this strategy are the potential drug ixabepilone which is an analogue of the natural product epothilone B and carfilzomib which is derived from epoxomicin and eravacycline derived from tetracycline. Cabergoline is derived from a number of ergot alkaloids one of which is lysergic acid and Simvastatin is based on Lovastatin.
