Posters
April, 2023
SMARCA2 degraders promote differentiation and inhibit proliferation in AML models
Anjana Agarwal, Koichi Ito, Olusola Peace Osinubi, KomaliVykuntam, Norman Fultang, Neha Bhagwat, Diane Heiser, Kris Vaddi, Peggy Scherle
April, 2023
Development of Pharmacodynamic Assays for Quantifying SMARCA2 Protein Degradation and Target Gene Expression in Response to a SMARCA2 Degrader (PRT3789)
Andrew Moore, Carly Bachner, Lalitha Srinivasan, Pradeep Kurup, Alex Grego, Caroline Vitkovitsky, Koichi Ito, Neha Bhagwat, Peggy Scherle
April, 2023
A Phase 1, Open-Label, Dose-Escalation Study of PRT1419, a Selective Induced MCL-1 Inhibitor, in Patients With Advanced/Metastatic Solid Tumors
Gerald S. Falchook, Manish R. Patel, Meredith McKean, Alexander Philipovskiy, Neha Bhagwat, Rachel Chiaverelli, William Sun, Michael Fossler, William Novotny, Michael Kurman, Sarah Rowe, Deborah Hunter, Mohammed Milhem
April, 2023
The Brain Penetrant CDK4/6 Inhibitor, PRT3645, is Highly Effective in Combination with Targeted Therapies in Preclinical Models of NSCLC, CRC and HER2-positive Breast Cancer
Yue Zou, Srijita Dhar, Kirsten Gallagher, Andrew Buesking, Sarah Pawley, Ryan Holmes, Xiaowei Wu, Katarina Rohlfing, Min Wang, Joseph Rager, Tom Emm, Stefan Ruepp, Miles Cowart, Jing Ni, Jean Zhao, Bruce Ruggeri, Andrew Combs, Kris Vaddi, Sandy Geeganage, Ashish Juvekar, Sang Hyun Lee, Peggy Scherle
April, 2023
Selective and orally bioavailable SMARCA2 targeted degraders induce synthetic lethality in SMARCA4-deficient solid tumor
Koichi Ito, Artem Shvartsbart, Joseph Rager, Anjana Agarwal, Michael Hulse, KomaliVykuntam, Min Wang, Justin Kurian, Miles Cowart, Joy Cote, Monisha Sivakumar, Jack Carter, Jessica Burtell, Alex Grego, Andrew Moore, Neha Bhagwat, Stefan Ruepp, Tom Emm, Liang Lu, Philip Pitis, Corey Basch, KlareBersch, Song Mei, Raul Leal, John Rose, Danielle Roth, ChaoyiXu, GanfengCao, Kris Vaddi, Sandy Geeganage, Bruce Ruggeri, Andrew Combs, Peggy Scherle
April, 2023
Combination therapy with selective SMARCA2 (BRM) degraders for treatment of SMARCA4 (BRG1)-deficient cancers
Michael Hulse, Margot Elkins, Jessica Burtell, KomaliVykuntam, Philip Pitis, Liang Lu, Kris Vaddi, Andrew Combs, Koichi Ito, Peggy Scherle
April, 2023
MCL1 inhibitor PRT1419 Demonstrates Antitumor Activity in PBRM1-altered Clear Cell Renal Cancer and Synergizes with Standard of Care Agents
Norman Fultang, Ashley M. Schwab, Brian Vidal Torres, Alexander Grego, Stephanie Rodgers, Diane Heiser, Kris Vaddi, Neha Bhagwat, Peggy Scherle
April, 2023
A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT2527, a CDK9 Inhibitor in Adult Patients With Advanced Solid Tumors
Jason T. Henry, Douglas Orr, Atrayee Basu-Mallick, Alex Spira, Christine Lihou, William Sun, Neelesh Sharma, Peggy Scherle, Rachel Chiaverelli, Manish R. Patel
December, 2022
PRT2527, a Novel, Highly Selective Cyclin-Dependent Kinase 9 (CDK9) Inhibitor, Has Potent Anti-Leukemic Activity in Preclinical Models of Lymphoid Malignancies
Neha Bhagwat, Bruce Ruggeri, Yang Zhang, YaronMosesson, Clare Killick-Cole, Veena Jagannathan, Peggy Scherle
March, 2022
PRT2527, a novel highly selective cyclin-dependent kinase 9 (CDK9) inhibitor, is active in preclinical models of prostate cancer
Elisa Federici, Gianluca Civenni, Aleksandra Kokanovic, Giada Sandrini, Luca Guarrera, Simone Mosole, Alessia Cacciatore, Valeria Uboldi, Manuel Lessi, Giovanni Papa, Domenico Albino, Elisa Storelli, Jessica Merulla, Andrea Rinaldi, Marco Bolis, Yang Zhang, Kris Vaddi, Peggy Scherle, Bruce Ruggeri, Giuseppina M. Carbone, Carlo V. Catapano
March, 2022
Brain Penetrant CDK4/6 Inhibitor PRT3645 Demonstrates Anti-tumor Activity and Enhances Survival in Glioblastoma and Breast Cancer Brain Metastasis Models
Ashish Juvekar, Yang Zhang, Andrew Buesking, Min Wang, Dave Rominger, Joseph Rager, Stefan Ruepp, Kirsten Gallagher, Yue Zou, Miles Cowart, Xiaowei Wu, Sarah Pawley, Ryan Holmes, William Gowen-MacDonald, Kris Vaddi, Andrew Combs, Bruce Ruggeri, Peggy Scherle
March, 2022
Preclinical Characterization of PRT3789, a Potent and Selective SMARCA2 Targeted Degrader
Michael Hulse, Anjana Agarwal, Min Wang, Jack Carter, Monisha Sivakumar, Brian Vidal, Justin Brown, Andrew Moore, Alexander Grego, Neha Bhagwat, Joseph Rager, Liang Lu, Corey Basch, Klare Bersch, Chaofeng Dai, Philip Pitis, Andrew Combs, Bruce Ruggeri, Kris Vaddi, Peggy Scherle, Koichi Ito
March, 2022
Combination of the MCL1 Inhibitor PRT1419 and SMARCA2 Degrader PRT3789 Shows Combinatorial Benefit in SMARCA4-Deleted Lung Cancer
Norman Fultang, Neha Bhagwat, Diane Heiser, Alexander Grego, Michael Hulse, Venkat Thodima, Koichi Ito, Kris Vaddi, Bruce Ruggeri, Peggy Scherle
December, 2021
A Phase 1 Dose Escalation Study of Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor PRT543 in Patients With Myeloid Malignancies
Manish R. Patel, Varun Monga, Shekeab Jauhari, Don Ambrose Stevens, Lucia Masarova, Meredith McKean, David Mauro, John Viscusi, Peggy Scherle, Neha Bhagwat, Andrew Moore, William Sun, Rachel Chiaverelli, Eric Mintah, Rajneesh Nath, Eytan Stein, Neil Palmisiano, Grerk Sutamtewagul, Srdan Verstovsek. 63rd ASH Annual Meeting and Exposition; December 11-14, 2021.
October, 2021
A phase 1 dose-escalation study of protein arginine methyltransferase 5 (PRMT5) inhibitor PRT543 in patients with advanced solid tumors and lymphoma
Meredith McKean, Manish R Patel, Robert Wesolowski, Renata Ferrarotto, Eytan M. Stein, Alexander N Shoushtari, David Mauro, John Viscusi, Peggy Scherle, Neha Bhagwat, William Sun, Rachel Chiaverelli, Eric Mintah, Shekeab Jauhari, Laura Finn, Neil D. Palmisiano, Robert A Baiocchi. AACR-NCI-EORTC Annual Meeting 2021; October 7-10, 2021.
October, 2021
A phase 1 dose-escalation study of protein arginine methyltransferase 5 (PRMT5) brain-penetrant inhibitor PRT811 in patients with advanced solid tumors, including recurrent high-grade gliomas
Gerald S. Falchook, Jon Glass, Varun Monga, Pierre Giglio, David Mauro, John Viscusi. Peggy Scherle, Neha Bhagwat, William Sun, Rachel Chiaverelli, Eric Mintah, Lydia Clements, Tanner M. Johanns, Meredith McKean. AACR-NCI-EORTC Annual Meeting 2021; October 7-10, 2021.
October, 2021
PRT2527 is a potent and selective CDK9 inhibitor that demonstrates anti-cancer activity in preclinical models of hematological malignancies and solid tumors with MYC amplification
Yang Zhang, Liang Lu, Min Wang, Dave Rominger, Stefan Ruepp, Kirsten Gallagher, William Gowen-MacDonald, Chaofeng Dai, Miles Cowart, Andrew Combs, Carlo Catapano, Bruce Ruggeri, Peggy Scherle, Kris Vaddi. AACR-NCI-EORTC Annual Meeting 2021; October 7-10, 2021.
April, 2021
Potent SMARCA2 targeted protein degraders induce genetic synthetic lethality in SMARCA4 deleted cancer
Koichi Ito, Anjana Agarwal, Philip Pitis, Min Wang, Jack Carter, Miles Cowart, Chaofeng Dai, William Gowen-MacDonald, Eliza Elliot, Brian Vidal, Jacob Spruance, Hsin-Yao Tang, Bruce Ruggeri, Liang Lu, Andrew Combs, Hong Lin, Peggy Scherle. AACR Annual Meeting 2021; April 10-15, 2021.
April, 2021
Preclinical Characterization of PRT1419, a Potent, Selective and Orally Bioavailable Inhibitor of MCL1
Neha Bhagwat, Alexander Grego, William Gowen-MacDonald, Min Wang, Miles Cowart, Xiaowei Wu, Dave Rominger, Joseph Rager, Tom Emm, Venkat Thodima, Raul Leal, Karl Blom, Jincong Zhuo, Andrew Combs, Bruce Ruggeri, Peggy Scherle, Kris Vaddi. AACR Annual Meeting 2021; April 10-15, 2021.
April, 2021
PRMT5 inhibition regulates alternative splicing and DNA damage repair pathways in SF3B1 R625C/G expressing uveal melanoma cells
Koichi Ito, Venkat Thodima, Jack Carter, Neha Bhagwat, Alexander Grego, Monisha Sivakumar, Joseph Rager, Mizue Terai, Takami Sato, Omar Abdel-Wahab, Bruce Ruggeri, Peggy Scherle, Kris Vaddi. AACR Annual Meeting 2021; April 10-15, 2021.
April, 2021
PRMT5 inhibition epigenetically regulates DNA repair pathways in cancer cells and sensitizes to chemotherapy and PARP inhibition
Koichi Ito, Jack Carter, Venkat Thodima, Mu Xu, Monisha Sivakumar, Neha Bhagwat, Joseph Rager, Jacob Spruance, Lin Zhang, Bruce Ruggeri, Peggy Scherle, Kris Vaddi. AACR Annual Meeting 2021; April 10-15, 2021.
April, 2021
PRMT5 inhibition downregulates MYB and NOTCH1 signaling, key molecular drivers of Adenoid Cystic Carcinoma
Jack Carter, Koichi Ito, Venkat Thodima, Neha Bhagwat, Joseph Rager, Andrew Moore, Nicole Spardy Burr, Jeffrey Kaufman, Kris Vaddi, Bruce Ruggeri, Peggy Scherle. AACR Annual Meeting 2021; April 10-15, 2021.
June, 2020
Preclinical Characterization of PRT543, a Potent and Selective Inhibitor of Protein Arginine Methyltransferase 5 (PRMT5), with Broad Antitumor Activity in In Vitro and In Vivo Models.
Bhagwat N, Zhang Y, Lin H, Wang M, Rominger D, Emm T, Chugani-Mahtani D, Angelis D, Shetty R, Leal R, Gowen-MacDonald W, Grego A, Luengo J, Manshouri T, Pastore F, Levine RL, Verstovsek S, Ruggeri B, Scherle P, and Vaddi K. AACR Virtual Annual Meeting II; June 22-24, 2020.
June, 2020
Discovery of PRT811, a Potent, Selective, and Orally Bioavailable Brain Penetrant PRMT5 Inhibitor for the Treatment of Brain Tumors.
Zhang Y, Lin H, Wang M, Angelis D, Hawkins M, Rominger D, Emm T, Thodima V, Luengo J, Ruggeri B, Scherle P, and Vaddi K. AACR Virtual Annual Meeting II; June 22-24, 2020.
Publications
November, 2020
PRMT5 Inhibition Modulates E2F1 Methylation and Gene Regulatory Networks Leading to Therapeutic Efficacy in JAK2V617F Mutant MPN
Pastore F, Bhagwat N, Pastore A, Radzisheuskaya A, Karzai A, Krishnan A, Li B, Bowman RL, Xiao W, Viny AD, Zouak A, Park YC, Cordner KB, Braunstein S, Maag JLV, Grego A, Mehta J, Wang M, Lin H, Durham BH, Koche RP, Rampal RK, Helin K, Scherle P, Vaddi K, and Levine RL. Cancer Discovery. 2020.
DOI: 10.1158/2159-8290.CD-20-0026
March, 2020
PRMT5 Regulates T Cell Interferon Response and is a Target for Acute Graft-Versus-Host Disease
Snyder K, Zitzer NC, Gao Y, Choe HK, Sell NE, Neidemire-Colley L, Ignaci A, Kale C, Devine RD, Abad MG, Pietrzak M, Wang M, Lin H, Zhang YW, Behbehani GK, Jackman JE, Garzon R, Vaddi K, Baiocchi RA, and Ranganathan P.
JCI Insight. 2020.
DOI: 10.1172/jci.insight.131099
October, 2019
Discovery of Potent and Selective Covalent Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors
Lin H, Wang M, Zhang YW, Tong S, Leal RA, Shetty R, Vaddi K and Luengo JI. ACS Med. Chem. Lett. 2019, 10: 1033-1038.
DOI: 10.1021/acsmedchemlett.9b00074
June, 2019
Nucleoside Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors
Lin H and Luengo JI. Bioorg. Med Chem Lett. 2019, 29: 1264-1269.
DOI: 10.1016/j.bmcl.2019.03.042