For a medicine to work, reaching diseased tissue is not always enough. Sometimes cells develop ways to remove the drug before it can do its job. This patent from Macau University of Science and Technology tackles that problem in rheumatoid arthritis, focusing on resistance to methotrexate, a widely used treatment. The researchers investigated ABCB5, a transporter protein that can act like a cellular pump, moving methotrexate back out of cells. Their experiments showed that when ABCB5 was overexpressed, cells accumulated less methotrexate and became more resistant to its effects. The team then explored sinomenine, a natural compound, and developed a series of new sinomenine derivatives designed to inhibit ABCB5. When combined with methotrexate, blocking this drug-efflux mechanism helped restore the medicine’s activity. One newly developed derivative, Compound 2, inhibited ABCB5 even at concentrations where sinomenine became less effective. The approach was also tested in drug-resistant arthritis models. At 30 mg/kg/day, Compound 2 combined with methotrexate reduced joint swelling and bone damage, while the same tested dose of sinomenine was less effective. MicroCT images on page 59 illustrate the differences in bone damage between treatment groups. The invention tackles a particularly frustrating barrier: when disease cells try to push an existing medicine back out, the answer may be to block the exit and give that medicine another chance to work.
When cells push a medicine back out, can another compound keep it inside?
Patent number: CN 115260098 B
Inventor(s): J. Huang, L. Liu, W. Luo, C. Qiu, W. Zhang, and C. Xia
Citation: J. Huang, L. Liu, W. Luo, C. Qiu, W. Zhang, and C. Xia, “ABCB5 抑制剂在制备多耐药性类风湿性关节炎治疗药物中的应用 [Application of ABCB5 inhibitors in preparing therapeutics for multidrug-resistant rheumatoid arthritis],” China Patent CN 115260098 B, Jun. 4, 2024.
