Genzyme Corporation

Oxana Beskrovnaya

Seng H Cheng

Andrew Charles Good

John Marshall

Bradford Hirth

Yibin Xiang

Cassandra Celatka

Ronald K Scheule

Markus Metz

Zhong Zhao

Elyse Bourque

Thomas A Natoli

Elina Makino

Katherine Jancsics

Herve Husson

Mario A Cabrera-Salazar

Renato Skerlj

John P Leonard

Renato Tony Skerlj

Sarah Moreno

Nikolai Bukanov

Nikolay O Bukanov

John Leonard

Andrew Good

Thomas Natoli

The invention relates to inhibitors of glucosylceramide synthase (GCS) of the Formula I: represented by the following structural formula or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.

Glucosylceramide synthase inhibitors

The invention relates to inhibitors of glucosylceramide synthase (GCS), such as Compound of Formula I, shown below, as defined herein, useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer. 

Provided herein are methods for determining the efficacy of treatment for polycystic kidney disease (PKD) in a patient, diagnosing PKD in a patient, staging PKD in a patient, and monitoring PKD in a patient. These methods include determining a single or multiple levels of one or more markers selected from the group of Proliferating Cell Nuclear Antigen (PCNA), cyclin D1, cyclin D3, MAPKERK kinase 1 (MEK), ribosomal protein S6 (S6), phosphorylated ribosomal protein S6 (pS6), extracellular signal-regulated kinase (ERK), phosphorylated extracellular signal-regulated kinase (pERK), protein kinase B (Akt), phosphorylated protein kinase B (pAkt), caspase-2, total S6, and retinoblastoma binding protein (RBBP). Also provided are kits that include at least three antibodies that specifically bind to one or more of these markers.

Biomarkers of polycystic kidney disease and uses thereof

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Southborough, MA, United States of America

Oxana Beskrovnaya