Maab Sultan

Submitted: 28 January 2026 You are already at the latest version Melanoma is one of the deadliest cancers and remains a major clinical challenge, especially in advanced stages where conventional therapies often show limited effectiveness. For example, one of the issues that melanoma patients face in clinics is acquired resistance to BRAF inhibitor therapy. We have previously reported that targeting spliceosomal proteins with small molecules results in apoptosis in melanomas.

Submitted: 09 September 2025 Posted: 11 September 2025 You are already at the latest version Melanoma is the most aggressive and deadliest form of skin cancer, and the current treatments of mel-anoma have many limitations, which necessitates discovering new compounds and targets for melanoma. Two probes, 2155-14 and 2155-18, were identified to induce apoptotic cell death, autophagy, and immune signaling modulation through hnRNPH1/H2-dependent mechanisms.

3. Results Synthesis and characterization of 2155-14 and 2155-18. The pyrrolidine diketopiperazine compounds, 2155-14 (JC-395) and 2155-18 (JC-408), were synthesized by standard solid phase synthesis with MBHA resins. Amino acids were coupled to amine on the resin using Boc-AA-OH or Fmoc-AA-OH (4 eq.), HOBt (4 eq.), and HATU (4 eq.) in DMF containing 10% DIEA at 25 °C, and the Boc or Fmoc group was deprotected by 55% TFA in DCM or 20% piperidine in DMF at 25 °C, respectively.