SPHK1 Inhibitor

Drug Name

SPHK-INBT

Classification

Small molecule

Development Status

Preclinical

Overview

SPHK-INBT is a small molecule drug that selectively targets the functional binding sites of SphK1. The anti-tumor mechanism of SPHK-INBT is mainly by inhibiting the activity of SphK1 to block the transformation of ceramide (Cer) and sphingosine (Sph) to sphingosine-1-phosphate (S1P). Increased ceramide and sphingosine levels can reduce chemotherapeutic resistance to cancer cells and decreased S1P can reduce the proliferation, vascularization and metastasis of tumors.

Target

Sphingosine kinase 1 (SphK) is an oncogenic sphingolipid-metabolizing enzyme that catalyzes the formation of sphingosine-1-phosphate (S1P), a lipid messenger with intracellular and extracellular functions. S1P can regulate proliferation and survival and has been established as a mitogenic factor involved in processes of oncogenesis. Therefore, SphK1 represents an important target for chemotherapy.

The elevated levels in SphK1 expression have been detected in many human cancers such as breast, lung, prostate and colon cancer. Furthermore, this increased SphK1 expression has been associated with poor prognosis in patients with, for example, glioblastoma and breast cancer.

Indication

SPHK-INBT alone or combined with chemotherapy was developed to treat a variety of cancers, including breast, lung and prostate.