BI-D1870 | p90 ribosomal S6 kinase inhibitor

BI-D1870 (501437-28-1) is an inhibitor of p90 ribosomal S6 kinase (RSK; IC₅₀’s = RSK1, 31 nM; RSK2, 24 nM; RSK3, 18 nM; RSK4, 15 nM) with selectivity over other AGC kinases.¹ It protected mice from experimental autoimmune encephalomyelitis suggesting a new strategy to treat multiple sclerosis.² BI-D1870 has also been found to alter mTORC1 signaling in an RSK-independent manner.³ BI-D1870 induced apoptosis in oral squamous cell carcinoma cells⁴, suppressed growth and induced apoptosis in pediatric medulloblastoma cell lines as well as sensitizing these lines to Sonic hedgehog agents⁵, and blocked cell proliferation and protein synthesis in dual BRAF and MEK inhibitor-resistant melanoma⁶. 

References/Citations:

1) Gopal et al. (2007), BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo; Biochem. J. 401 (Pt 1) 29
2) Takda et al. (2016), The ribosomal S6 kinase inhibitor BI-D1870 ameliorated experimental autoimmune encephalomyelitis in mice; Immunobiology 221 188
3) Roffe et al. (2015), Two widely used RSK inhibitors, BI-D1870 and SL0101, alter mTORC1 signaling in a RSK-independent manner; Cell Signal. 27 1630
4) Chiu et al. (2014), Antitumor effects of BI-D1870 on human oral squamous cell carcinoma; Cancer Chemother. Pharmacol. 73 237
5) Pambid et al. (2014), Overcoming resistance to Sonic hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma; Pediatr. Blood Cancer 61 107
6) Theodosakis et al. (2017), p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis; J. Invest. Dermatol. 137 2187