Indiana State University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Indiana University

Richard W Fitch

John W Daly

John J Turchi

Thomas F Spande

Herman J C Yeh

H Martin Garraffo

The invention provides novel nicotinic acetylcholine receptor agonists, for example, phantasmidine and derivatives thereof, for example a compound of formula I. Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acetylcholine receptor agonists. 

Nicotinic acetylcholine receptor agonists

Replication protein A (RPA) is a single-strand DNA-binding protein with essential roles in DNA replication, recombination and repair. Small molecule inhibitors (SMIs) with the ability to disrupt RPA binding activity to ssDNA have been identified and assessed using both lung and ovarian cancer cell lines. Lung cancer cell lines demonstrated increased apoptotic cell death following treatment with the SMI MCI13E, with IC50 values of &#x2dc;5 &#x3bc;M. The A2780 ovarian cancer cell line and the p53-null lung cancer cell line HI 299 were particularly sensitive to MCI13E treatment with ICvalues below 3 &#x3bc;M. Sequential treatment with MCI13E and cisplatin resulted in synergism, suggesting that decreasing RPA's DNA binding activity via a SMI may disrupt RPA's role in cell cycle regulation. Thus, RPA SMIs hold the potential to be used as single agent chemotherapeutics or in combination with current chemotherapeutic regimens to increase their efficacy.

Small molecule inhibitors of replication protein A that also act synergistically with cisplatin

The invention provides novel nicotinic acetylcholine receptor agonists, for example, phantasmidine and derivatives thereof, for example a compound of formula (I). Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acetylcholine for agonists. 

Growing community of inventors

Terre Haute, IN, United States of America

Richard W Fitch