LIT-927

LIT-927 is a locally and orally active CXCL12 neutraligand with anti-inflammatory effect, with a Ki of 267 nM for CXCL12 binding to its specific receptor CXCR4[1] .

LIT-927 is a locally and orally active CXCL12 neutraligand with anti-inflammatory effect, with a Ki of 267 nM for CXCL12 binding to CXCR4. Compounds 50, 57 (LIT-927), 65, and 67 are the most potent and soluble cyclic neutraligands identified in vitro and are representative of four novel chemotypes: pyrazoline, pyrimidinone, benzofuranone, and chromanone. LIT-927 is bound to a wide and accessible pocket, which is incompatible with the observed nanomolar binding affinities of our neutraligands[1].

LIT-927 (compound 57) reduces eosinophil recruitment in a murine model of allergic airway hypereosinophilia, LIT-927 is the only one to display inhibitory activity following oral administration. Combined with a high binding selectivity for CXCL12 over other chemokines, LIT-927 represents a powerful pharmacological tool to investigate CXCL12 physiology in vivo and to explore the activity of chemokine neutralization in inflammatory and related diseases[1].

Reference:

[1]. Regenass P, et al. Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia. J Med Chem. 2018 Sep 13;61(17):7671-7686.