Crisnatol (BW-A770U) is an experimental

anticancer An anticarcinogen (also known as a carcinopreventive agent) is a substance that counteracts the effects of a carcinogen or inhibits the development of cancer. Anticarcinogens are different from anticarcinoma agents (also known as anticancer or ant ...

agent known for its potential in inhibiting the growth of various solid tumors. Research has indicated that crisnatol acts as a DNA- intercalating agent, thereby disrupting the replication process in cancer cells. A Phase I

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

was conducted to assess its safety profile, pharmacokinetics, and potential efficacy in patients with solid malignancies. This study highlighted the drug’s ability to inhibit tumor growth, although associated toxicities were observed, necessitating further research to optimize its therapeutic window.

Mechanism of action

Crisnatol is a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

aromatic amine In organic chemistry, an aromatic amine is an organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be a ...

and a potent anticancer compound. It functions by intercalating into DNA and inhibiting

topoisomerase DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues in ...

activity, which leads to DNA damage and prevents cancer cells from proliferating. It primarily targets solid tumors and shows a higher affinity for

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

and

glioma A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...

cells. Due to its lipophilic properties, crisnatol can effectively penetrate the blood-brain barrier, making it a potential treatment for

brain tumors A brain tumor (sometimes referred to as brain cancer) occurs when a group of cells within the brain turn cancerous and grow out of control, creating a mass. There are two main types of tumors: malignant (cancerous) tumors and benign (non-cancero ...

Clinical trials

Crisnatol has undergone several Phase I and II clinical trials aimed at determining its

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

, safety profile, and efficacy against various types of

solid tumors A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

. Early studies demonstrated dose-limiting toxicities, primarily

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

and hematologic toxicity, which necessitated further research to optimize dosing schedules. In one Phase I trial, crisnatol mesylate was administered as a protracted infusion in patients with advanced solid malignancies, revealing a manageable toxicity profile and some evidence of tumor regression. More recent trials have explored combinations of crisnatol with other anticancer agents, such as

cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...

, to enhance its efficacy and minimize resistance.

Potential applications and challenges

Despite its promise, crisnatol faces challenges due to its side effects, which include neurotoxicity and dose-limiting hematologic toxicities. Research continues to focus on optimizing its therapeutic index and exploring potential applications in combination therapies. The ability of crisnatol to cross the blood-brain barrier has led to interest in its use against brain cancers, although further studies are needed to fully establish its efficacy and safety in this context.{{cn, date=February 2025

References

Secondary amines Diols Primary alcohols