The Drug Discovery Division conducts basic and translational research with a focus in oncology, infectious diseases and neuroscience. With a faculty and staff of approximately 75 scientists, we emphasize cutting-edge research on novel mechanisms and challenging targets with the goal of identifying new drugs for today’s most significant healthcare challenges.
In addition to our internal research efforts, the Division participates in many academic and industrial collaborations and research partnerships. And through the Alabama Drug Discovery Alliance, our work with investigators from the University of Alabama at Birmingham has resulted in a number of potential new drug therapies.
The Division is partially funded by multiple institutional and investigator grants from the National Institutes of Health and other federal institutions, including the Department of Defense. In addition, we have secured competitive funding from a range of private foundations including The Cystic Fibrosis Foundation, The Muscular Dystrophy Foundation, The Bright House Foundation, The Amyotrophic Lateral Sclerosis Association, and The Steven & Alexandra Cohen Foundation.
Southern Research’s Drug Discovery Division welcomes collaboration opportunities
with both academic and industrial research partners.
ADDA Discovery Pipeline
Through the Alabama Drug Discovery Alliance (ADDA), Southern Research collaborates closely with researchers at the University of Alabama at Birmingham (UAB) to leverage the strengths and capabilities of both institutions in addressing unmet medical needs. Established in 2008, the ADDA facilitates and expedites the discovery and development of new drug therapies.
Through internal and external funding sources, the ADDA advances promising discovery research originating in UAB and Southern Research labs through pre-clinical development. The alliance emphasizes research in the areas of oncology, infectious diseases, and CNS/neurological disorders, but also considers other programs in areas of unmet medical need.
Southern Research Discovery Pipeline
Therapy for Chronic Pseudomonas aeruginosa Infections
We are developing an engineered version of the filamentous Pf phage for the treatment of biofilm-related chronic P. aeruginosa infections. While highly resistant to antibiotics, P. aeruginosa biofilms are very accessible to Pf phage since Pf is normally found in biofilms. We are designing the phage to disrupt biofilms after infection. The engineered phage will destabilize the entire biofilm and induce its dispersion, making the P. aeruginosa susceptible to host immune defenses and lower-dose antibiotic treatment.
SRI-22138 for Pain
We have identified a series of opioid compounds with a greatly reduced side effect profile as compared to classic opioids such as morphine. SRI-22138 is the lead compound with strong agonism at the mu receptor subtype and strong antagonism at the delta receptor subtype. In vivo studies have shown that SRI-22138 has greatly reduced tolerance induction and abuse liability as compared to morphine.
PD1 Small Molecule Inhibitors for Oncology
Small molecule and peptide inhibitors of immune checkpoint systems offer several advantages over monoclonal antibodies, including lower cost and the potential for oral and topical uses. These advantages have the potential to increase the range of indications for these inhibitors beyond oncology. We have designed a series of peptides that inhibit PD1-PDL1 binding in a dose-dependent manner. Efforts are now underway to identify a peptide that is optimized for size, efficacy and stability.
We have also conducted a pilot high-throughput screen and identified several confirmed hits. Plans are underway to conduct a larger screen of 250,000 compounds.
Patents & Publications
DDS Patents Q3 2016
“Methods and Compositions for Inhibiting PD-1:PD-L1 Interaction”
“Benzimidazole Compounds, Use as Inhibitors of WNT Signaling Pathway in Cancers, and Methods for Preparation Thereof”
“Pyrrolopyrimidine Compounds, Use as Inhibitors of the Kinase LRRK2, and Methods for Preparation Thereof”
“Synergistic Effect of Gefitinib and MEK1 Inhibitors in Colon Cancer”
Mutyam, V.; Du, M.; Xue, X.; Keeling, K. M.; White, E. L.; Bostwick, J. R.; Rasmussen, L.; Liu, B.; Mazur, M.; Hong, J. S.; Falk, L. E.; Liang, F.; Shang, H.; Mense, M.; Suto, M. J.; Bedwell, D. M.; Rowe, S. M.
Am. J. Respir. Crit. Care Med. 2016, 194: 1092-1103
Arend, R. C., Londono-Joshi, A. I., Gangrade, A., Katre, A. A., Kurpad, C., Li, Y., Samant, R. S., Li, P. K., Landen, C. N., Yang, E. S., Hidalgo, B., Alvarez, R. D., Straughn, J. M., Forero, A., and Buchsbaum, D. J. (2016)
Schreiber, S. L.; Kotz, J. D.; Li, M.; Aube, J.; Austin, C. P.; Reed, J. C.; Rosen, H.; White, E. L.; Sklar, L. A.; Lindsley, C. W.; Alexander, B. R.; Bittker, J. A.; Clemons, P. A.; de, S. A.; Foley, M. A.; Palmer, M.; Shamji, A. F.; Wawer, M. J.; McManus, O.; Wu, M.; Zou, B.; Yu, H.; Golden, J. E.; Schoenen, F. J.; Simeonov, A.; Jadhav, A.; Jackson, M. R.; Pinkerton, A. B.; Chung, T. D.; Griffin, P. R.; Cravatt, B. F.; Hodder, P. S.; Roush, W. R.; Roberts, E.; Chung, D. H.; Jonsson, C. B.; Noah, J. W.; Severson, W. E.; Ananthan, S.; Edwards, B.; Oprea, T. I.; Conn, P. J.; Hopkins, C. R.; Wood, M. R.; Stauffer, S. R.; Emmitte, K. A.