ACT-1004-1239

WW-12, which was derived from the chemical modifications of conolidine, became a novel small-molecule pain modulator by activating ACKR3, which in turn boosted endogenous opioid peptides for the classical opioid receptors.ACKR3 antagonist ACT-1004-1239 from Idorsia Pharmaceuticals Ltd. has demonstrated the ability to treat cancer, acute lung injury/ARDS, and autoimmune diseases, including multiple sclerosis. The outcomes of these clinical trials will direct the development and indications of future ACKR3 modulators.

In general, we identified a novel positive feedback loop between CXCR7 and the Hippo/YAP axis, and blockade of CXCR7 could be a plausible strategy for gastric cancer.

These results confirm the dual mode of action of ACT-1004-1239 in a therapeutic setting in murine models of MS, providing both an immunomodulatory effect by reducing neuroinflammation and promyelination by accelerating myelin repair.

The first in class CXCR7 antagonist ACT-1004-1239 demonstrated properties in favor of further clinical development in inflammatory demyelinating diseases such as MS.

In vitro, ACT-1004-1239 promoted the maturation of OPCs into myelinating oligodendrocytes. These results provide evidence that ACT-1004-1239 both reduces neuroinflammation and enhances myelin repair substantiating the rationale to explore its therapeutic potential in a clinical setting.