Drug intelligence / Profile preview

cilostazol + methotrexate

Development stage
Phase 3
Lead developer
Otsuka Pharmaceutical
Modality
Small Molecules
Administration
Oral
01

Overview

Cilostazol + methotrexate is a combination therapy being investigated for the treatment of rheumatoid arthritis (RA). This combination works through complementary mechanisms to suppress inflammation and prevent joint damage. Cilostazol is a quinolinone derivative that functions as an antiplatelet agent and vasodilator, primarily through phosphodiesterase 3 inhibition which increases cAMP levels. Methotrexate (MTX) is a well-established disease-modifying antirheumatic drug (DMARD). When used together, they effectively suppress proliferation and enhance apoptosis of synovial fibroblasts while significantly reducing inflammatory cytokine production including TNF-α, IL-1β, IL-6, and MCP-1 in an additive manner. The combination therapy has shown promise in both laboratory studies with synovial fibroblasts from RA patients and in mouse models of collagen-induced arthritis.

02

Targets

DHFR (Dihydrofolate reductase)PDE3IL1B (Interleukin-1 beta)IL-6 (Interleukin 6)CCL2 (C-C motif chemokine 2)NF-κBTNFA (Tumor necrosis factor alpha (soluble))

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