Structure-guided discovery of a dual JAK2/RAGE modulator reveals a computationally driven strategy for targeting convergent oncogenic signaling in renal cell carcinoma. (PubMed, J Comput Aided Mol Des) - Oct 16, 2026 - "It inhibited JAK2 in an ATP-competitive manner (IC₅₀ = 60.23 nM; ruxolitinib IC₅₀ = 1.69 nM), with ATP-dependent shifts (35.04 → 74.09 → 305.6 nM) and thermal stabilization (ΔTm +1.50 °C)...It suppressed STAT3 (IC₅₀ 412.3-813.2 nM) and NF-κB (IC₅₀ 435.7-1031 nM) signaling, reduced IL-6/IL-8 secretion, induced caspase-3/7 activation (EC₅₀ 662.4-862.9 nM), and inhibited migration (up to 83%). Collectively, RJS6641 functions as a JAK2 inhibitor with additional modulation of RAGE-associated signaling, leading to coordinated suppression of STAT3/NF-κB pathways and anti-tumor effects in RCC, supporting further in vivo and selectivity evaluation."
Journal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CASP3 • CASP7 • CXCL8 • IL6 • JAK2
|
|
Mesfer Mohammad-Al-Shahrani; Mohammad Abohassan; Prasanna Rajagopalan
|