XL139 (BMS-833923)

XL139 (BMS-833923) is a small molecule inhibitor of Smoothened (SMO), a component of the hedgehog (Hh) signaling pathway. The Hh signaling pathway plays a critical role in cell differentiation and proliferation. Dysregulation of this pathway contributes to uncontrolled growth of some tumors and resistance to chemotherapy treatments.1,2 The Hh pathway may be a regulator of cancer stem cells (CSCs), which are discrete tumor cell populations that display self-renewal and tumorigenic properties2. A number of human cancers are associated with mutations in the Hh pathway, overexpression of pathway components, or CSCs with Hh pathway activation1,2. Signaling through the Hh pathway involves Smoothened (SMO), a receptor associated with initiation of growth signals, and Patched 1, a receptor that inhibits signaling by SMO1,2.

Co-developed with BMS.

Related Clinical Trials

Phase Clinical Trial Status
Phase 1b A Study of BMS-833923 With Cisplatin and Capecitabine in Inoperable, Metastatic Gastric, Gastroesophageal, or Esophageal Adenocarcinomas Recruiting
Phase 1b A Study of BMS-833923 With Carboplatin and Etoposide Followed by BMS-833923 Alone in Subjects With Extensive-Stage Small Cell Lung Cancer Recruiting
Phase 1b Multiple Ascending Dose (MAD) Combination in Subjects With Multiple Myeloma Recruiting
Phase 1 A Phase 1 Study of BMS-833923 (XL139) in Subjects With Advanced or Metastatic Cancer Recruiting

 

  1. Rubin LL and de Sauvage FJ.  Targeting the hedgehog pathway in cancer.  Nat RevDrug Discov. 2006; 5 (12):1026-1033.
  2. Sims-Mourtada J, Izzo JG, Ajani J, et al.  Sonic hedgehog promotes multiple drug resistance by regulation of drug transport.  Oncogene.  2007; 26 (38):5674-5679.