Crisnatol

Crisnatol (BW-A770U) is an experimental anticancer 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.^[1] A Phase I clinical trial 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.^[2]

Crisnatol

Clinical data
ATC code	none
Identifiers
IUPAC name 2-(Chrysen-6-ylmethylamino)-2-methylpropane-1,3-diol
CAS Number	96389-68-3 Y
PubChem CID	57062
ChemSpider	51449 Y
UNII	2J71UR51UE
CompTox Dashboard (EPA)	DTXSID10242217
Chemical and physical data
Formula	C23H23NO2
Molar mass	345.442 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(CO)(CO)NCc1cc2c3ccccc3ccc2c4c1cccc4
InChI InChI=InChI=1S/C23H23NO2/c1-23(14-25,15-26)24-13-17-12-22-18-7-3-2-6-16(18)10-11-21(22)20-9-5-4-8-19(17)20/h2-12,24-26H,13-15H2,1H3 Y Key:SBRXTSOCZITGQG-UHFFFAOYSA-N Y

Mechanism of action

Crisnatol is a synthetic aromatic amine and a potent anticancer compound. It functions by intercalating into DNA and inhibiting topoisomerase activity, which leads to DNA damage and prevents cancer cells from proliferating. It primarily targets solid tumors and shows a higher affinity for melanoma and glioma cells. Due to its lipophilic properties, crisnatol can effectively penetrate the blood-brain barrier, making it a potential treatment for brain tumors.^[3]

Clinical trials

Crisnatol has undergone several Phase I and II clinical trials aimed at determining its pharmacokinetics, safety profile, and efficacy against various types of solid tumors. Early studies demonstrated dose-limiting toxicities, primarily neurotoxicity 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.^[4]

More recent trials have explored combinations of crisnatol with other anticancer agents, such as cisplatin, to enhance its efficacy and minimize resistance.^[5]

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.^[6]

References

1. U.S. patent 4,719,046
2. Villalona-Calero MA, Petit T, Kuhn J, Cobb P, Kraynak M, Eckhardt SG, et al. (November 1999). "A phase I and pharmacological study of protracted infusions of crisnatol mesylate in patients with solid malignancies". Clinical Cancer Research. 5 (11): 3369–78. PMID 10589747.
3. Veal, G.J. (1999). "DNA intercalation and topoisomerase inhibition by crisnatol". Anti-Cancer Drugs. 10 (4): 367–375. doi:10.1097/00001813-199904000-00006. PMID 10231547.
4. Villalona-Calero MA, Petit T, Kuhn J, et al. (1999). "A phase I and pharmacological study of protracted infusions of crisnatol mesylate in patients with solid malignancies". Clinical Cancer Research. 5 (11): 3369–78. PMID 10589747.
5. Levine, E.G. (2000). "Crisnatol in combination therapy with cisplatin: A pharmacokinetic and phase II study". Investigational New Drugs. 18 (3): 239–246. doi:10.1023/A:1006499628198. PMID 10809156.
6. Haase, G.M. (2012). "Potential applications of crisnatol in brain tumor therapy". Current Cancer Drug Targets. 12 (8): 899–909. doi:10.2174/156800912803251197. PMID 22894893.