Our Science

We are a clinical-stage precision oncology company focused on discovering and developing small molecule therapies optimized to target the key driver mechanisms in cancers with high unmet need. By leveraging our core competencies in cancer biology and medicinal chemistry, combined with our target class and technology platform-agnostic approach, we have built an efficient, fully-integrated drug discovery engine to identify compelling biological targets and create new chemical entities that we rapidly advance into clinical development.

PRMT5 Inhibitors 

PUBLICATIONS

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

PRMT5 Inhibition Modulates E2F1 Methylation and Gene Regulatory Networks Leading to Therapeutic Efficacy in JAK2V617F Mutant MPN

Pastore F, Bhagwat N, Krishnan A, Pastore A, Li B, Bowman RL, Xiao W, Viny AD, Karzai A, Zouak A, Park YC, Cordner K, Braunstein S, Grego A, Mehta J, Durham BH, Koche RP, Maag J, Scherle P, Vaddi K, and Levine RL.  Blood.  2019, 134(Supplement_1): 473.

DOI: 10.1182/blood-2019-127122

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

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

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

POSTERS

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.

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.

Related Publications 

The Regulation, Functions and Clinical Relevance of Arginine Methylation
Guccione E and Richard S.  Nat Rev Mol Cell Bio. 2019, 20: 642-657.

DOI:  10.1038/s41580-019-0155-x

Disordered Methionine Metabolism in MTAP/CDKN2A-deleted Cancers Leads to Dependence on PRMT5
Mavrakis KJ, McDonald III ER, Schlabach MR, Billy E, Hoffman GR, deWeck A, Ruddy DA, Venkatesan K, Yu J, McAllister G, Stump M, deBeaumont R, Ho S, Yue Y, Liu Y, Yan-Neale Y, Yang G, Lin F, Yin H, Gao H, Kipp DR, Zhao S, McNamara JT, Sprague ER, Zheng B, Lin Y, Cho YS, Gu J, Crawford K, Ciccone D, Vitari AC, Lai A, Capka V, Hurov K, Porter JA, Tallarico J, Mickanin C, Lees E, Pagliarini R, Keen N, Schmelzle T, Hofmann F, Stegmeier F, and Sellers WR. Science. 2016, 351: 1208-1213.

DOI: 10.1126/science.aad5944

Coordinated Splicing of Regulatory Detained Introns Within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma
Braun CJ, Stanciu M, Boutz PL, Patterson JC, Calligaris D, Higuchi F, Neupane R, Fenoglio S, Cahill DP, Wakimoto H, Agar NYR, Yaffe MB, Sharp PA, Hemann MT, and Lees JA.  Cancer Cell. 2017, 32: 411-426.

DOI:  10.1016/j.ccell.2017.08.018

Adenoid Cystic Carcinoma: A Review of Recent Advances, Molecular Targets, and Clinical Trials
Dillon PM, Chakraborty S, Moskaluk CA, Joshi PJ, and Thomas CY.  Head Neck.  2016, 38: 620-627.

DOI: 10.1002/hed.23925