TL4-12

TL4-12 is a selective small molecule inhibitor of **germinal center kinase (GCK)**, also known as **MAP4K1**. It was identified as a potential therapeutic strategy for **multiple myeloma (MM)**, particularly in cases harboring **RAS mutations** (NRAS, KRAS, or BRAF), which are found in up to 50% of patients. TL4-12 works by inhibiting the kinase activity of GCK, which subsequently blocks the **MKK4/7-JNK** signaling pathway. This inhibition leads to the impaired degradation of critical survival and transcription factors, including **IKZF1**, **IKZF3**, **BCL-6**, and **c-MYC**. Preclinical studies have demonstrated that TL4-12 dose-dependently inhibits MM cell proliferation and induces apoptosis, suggesting it may also serve as an alternative therapy to overcome resistance to immunomodulatory drugs (IMiDs).