RGNCY-0071 (9# Jak2 inhibitor)

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Compound 9# is a selective and potent inhibitor of Jak2.  It suppresses Jak2/STAT3 signalling in peritoneal and THP-1 macrophages and directs them towards the pro-inflammatory M1-like phenotype.  9# can reverse the phenotype of TAM from M2- to M1-like by promoting IL-12 expression in ex vivo TAM cultures and in vivo tumor models.  It also inhibits the induction of Treg in vitro and in vivo by blocking Jak2 signalling.  This compound potently increases the frequency and anti-tumor activity of CD4+ and CD8+ T lymphocytes which leads to the effective suppression of tumor growth, making it an ideal candidate for cancer immunotherapy.  Jak2 IC50 = 2.35 + 0.29 µM.

SMILE:  O=C(C(F)(F)[C@@H](C(F)(F)F)N[S@](C(C)(C)C)=O)C1=CC=C(OC)C=C1

Systematic Name:  (S)-2-methyl-N-((S)-1,1,1,3,3-pentafluoro-4-(4-methoxyphenyl)-4-oxobutan-2-yl)propane-2-sulfinamide

Molecular Weight: 387.37

Formula:  C15H18F5NO3S

PMID:  28859967

Tags: Cancer, JAK2, CD4, Tumor, immunotherapy, RGNCY-0071