501437-28-1 Usage
Description
BI-D1870 is an inhibitor of p90 ribosomal S6 kinase (RSK), which is involved in various cellular processes such as growth, survival, and motility. It selectively targets the four vertebrate isoforms of RSK (RSK1-4) with IC50 values ranging from 15 to 31 nM. BI-D1870 has been shown to protect mice from experimental autoimmune encephalomyelitis, alter mTORC1 signaling in an RSK-independent manner, induce apoptosis in oral squamous cell carcinoma cells, suppress growth and induce apoptosis in pediatric medulloblastoma cell lines, and block cell proliferation and protein synthesis in dual BRAF and MEK inhibitor-resistant melanoma.
Uses
Used in Pharmaceutical Industry:
BI-D1870 is used as an inhibitor of p90 ribosomal S6 kinase (RSK) for its potential therapeutic applications in various diseases, including multiple sclerosis, cancer, and other conditions involving abnormal cell growth and survival.
Used in Cancer Research:
BI-D1870 is used as a research tool to study the role of RSK in cancer cell growth, survival, and motility. It has been shown to induce apoptosis in oral squamous cell carcinoma cells, suppress growth and induce apoptosis in pediatric medulloblastoma cell lines, and block cell proliferation and protein synthesis in dual BRAF and MEK inhibitor-resistant melanoma.
Used in Neurological Research:
BI-D1870 is used as a research tool to investigate the role of RSK in neurological disorders, such as multiple sclerosis. It has been shown to protect mice from experimental autoimmune encephalomyelitis, suggesting its potential use in developing new treatment strategies for multiple sclerosis.
Used in Cell Signaling Research:
BI-D1870 is used as a research tool to study the role of RSK in cell signaling pathways, particularly those involving mTORC1. It has been found to alter mTORC1 signaling in an RSK-independent manner, providing insights into the complex regulatory networks within cells.
Enzyme inhibitor
This cell-permeant, ATP-competitive inhibitor (FW = 391.42 g/mol; CAS
501437-28-1: Solubility = 78 mg/mL DMSO; <1 mg/mL H2O), also known
as 2-[ (3,5-difluoro-4-hydroxyphenyl) amino]-7,8-dihydro-5,7-dimethyl-8- (3-
methylbutyl) -6 (5H) -pteridinone, targets the p90 Ribosomal protein S6
Kinase a-1, 2, 3, and 4, or RSK1, RSK2, RSK3, and RSK4, with IC50 values
of 31 nM, 24 nM, 18 nM, and 15 nM, respectively. RSK isoforms are
activated by Extracellular-signal-Regulated Kinases ERK1 and ERK2 in
response to growth factors, phorbol esters and other agonists. BI-D1870
shows 10x to 100x selectivity for RSK over MST2, GSK-3β, MARK3, CK1
and Aurora B protein kinases. When tested in vitro, BI-D1870 exhibits IC50
values for inhibits RSK1, RSK2, RSK3 and RSK4 are in the 10–30 nM.
Although assumed to be a remarkably specific inhibitor of RSK isoforms,
with a >500-fold greater selectivity over nine other AGC kinases, later work
assessing the ability of BI-D1870 to protect enzyme active sites from
alkylation demonstrated that several other kinases interact with BI-D1870
. Subsequent direct activity assays confirmed that Slk, Lok and Mst1
protein kinases are inhibited by BI-D1870 and that phosphorylation of some
of their substrates is blocked by BI-D1870 in living cells. Such results
suggest that the specificity of BI-D1870 cannot be taken for certain.
References
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
Check Digit Verification of cas no
The CAS Registry Mumber 501437-28-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,0,1,4,3 and 7 respectively; the second part has 2 digits, 2 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 501437-28:
(8*5)+(7*0)+(6*1)+(5*4)+(4*3)+(3*7)+(2*2)+(1*8)=111
111 % 10 = 1
So 501437-28-1 is a valid CAS Registry Number.
InChI:InChI=1/C19H23F2N5O2/c1-10(2)5-6-26-11(3)18(28)25(4)15-9-22-19(24-17(15)26)23-12-7-13(20)16(27)14(21)8-12/h7-11,27H,5-6H2,1-4H3,(H,22,23,24)
