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BMS-986195 (BMS986195) is a novel potent, selective, covalent, irreversible inhibitor of Bruton’s tyrosine kinase (BTK), >5,000-fold selective over all kinases outside of the Tec family, and selectivity ranges 9- to 1010-fold within the Tec family; potently inhibits antigen-dependent interleukin-6 production, CD86 expression and proliferation in B cells (IC50<1 nM); demonstrates robust efficacy in murine models of RA including CIA and CAIA, protecting against clinically evident disease, histologic joint damage and bone mineral density loss.

Rheumatoid Arthritis

Phase 1 Clinical




PLX5622 (PLX-5622) is a potent, selective, orally active inhibitor of CSF1R tyrosine kinase (c-Fms) activity with Ki of 5.9 nM, 60-fold less potency against KIT; dispalys least 50-fold selectivity over 4 related kinases, and over 100-fold selectivity against a panel of 230 kinases; prevents microglial plaque association and improves cognition in 3xTg-AD mice, also depletes microglia and alleviates the catatonic symptoms of Cnp mutants.

Rheumatoid Arthritis

Phase 1 Discontinued




Edicotinib (JNJ 40346527, PRV 6527) is a potent, selective, orally bioavailable CSF-1R inhibitor with IC50 of 3.2 nM; shows weak affinity for KIT and FLT3 (IC50= 20 nM and 190 nM, respectively); reduces the levels of EMT-associated genes, stem cell markers and chemoresistance genes, produces strong chemo-sensitizing effects in vitro and in vivo.

Rheumatoid Arthritis

Phase 2 Clinical




BMS-189453 (BMS189453, BMS453) is a synthetic retinoid that acts as an agonist of RARβ and an antagonist of RARα and RARγ; binds to RAR receptors and transrepresses AP-1, inhibits the growth of normal breast cells (HMEC and 184) and T47D breast cancer cells; increases p21, decrease CDK2 kinase activity, which in turn leads to hypophosphorylation of Rb and G1 arrest.

Rheumatoid Arthritis





Poseltinib (HM-71224, LY-3337641) is a potent and selective, covalent inhibitor of Btk with IC50 of 1.95 nM; also inhibits BMX, TEC, TXK, EGFR in biochemical sense (IC50=0.3-2.5 nM); effectively inhibits the phosphorylation of Btk and PLCγ2, and inhibits expression of CD40, CD69, and CD86 by activated primary human B cells with IC50 of 4.2, 4.2, and 7.7 nM, respectively; inhibited the production of TNF-α, IL-6, and IL-1β by human monocytes, and osteoclast formation by human monocytes; ameliorates arthritis in a mouse model.

Rheumatoid Arthritis

Phase 1 Clinical




Adavivint (SM-04690, SM 04690, SM04690) is a novel small molecule Wnt pathway inhibitor with EC50 of 3 nM in vitro; induces hMSC differentiation into mature, functional chondrocytes and decreases cartilage catabolic marker levels; significantly improves Osteoarthritis Research Society International (OARSI) histology scores and biomarkers in a rodent OA model.

Rheumatoid Arthritis

Phase 2 Clinical




BMS-986142 (BMS 986142) is a potent, selective and reversible BTK inhibitor with IC50 of 0.5 nM; displays 20-60-fold selectivity over Tec family kinases, >10,000-fold selectivity over JAK2; potently inhibits signaling and functional end points, including calcium flux (IC50=9 nM), production of cytokines, proliferation, and surface expression of CD86 (IC50=3-4 nM); potently inhibits BCR-stimulated expression of CD69 on B cells in human whole blood with IC50 of 90 nM; exhibits excellent in vivo properties and efficacy, and a very desirable tolerability and safety profile.

Rheumatoid Arthritis

Phase 2 Clinical

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