406208-42-2 Usage
Uses
ACHP is an IkB kinase inhibitor, which has dose-dependently inhibited cell growth with inhibition of phosphorylation of IκBα/p65 and NF-κB DNA-binding, down-regulation of NF-κB target genes and induced apoptosis in human myeloma cell lines.
Biological Activity
achp is an iκb kinase inhibitor. nuclear factor-kb (nf-kb) involved in cell survival and proliferation of multiple myeloma has been well established.
in vitro
achp is selective for ikkα and ikkβ over ikk3, syk and mapkkk4 (ic50 > 20 μm), dna binding activity of nf-κb is inhibited. achp is an effective blockade nf-κb pathway in multiple myeloma cell lines, and induces cell growth arrest and apoptosis. it was observed that nf-kb is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. in addition, it was found the phosphorylation of p65 subunit of nf-kb besides the phosphorylation of ikba and the activation of nf-kb dna binding and that various target genes of nf-kb including bcl-xl, xiap, c-iap1, cyclin d1, and il-6 are up-regulated. 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinenitrile (achp) is a novel ikb kinase inhibitor. treatment of myeloma cells with achp showed the cell growth was efficiently inhibited (ic50 values ranging from 18 to 35 mmol/l) concomitantly with inhibition of the phosphorylation of ikba/p65 and nf-kb dna-binding, down-regulation of the nf-kb target genes, and then induction of apoptosis. in addition, the treatment of achp potentiated the cytotoxic effects of vincristine and melphalan (l-phenylalanine mustard), conventional antimyeloma drugs. these findings suggest that by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of nf-kb, ikb kinase inhibitors such as achp can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents.
Enzyme inhibitor
This novel IKK inhibitor (FW = 364.44 g/mol; CAS 406208-42-2; Soluble to 20 mM in DMSO), also named 2-amino-6-[2-(cyclopropylmethoxy)-6hydroxyphenyl]-4-(4-piperidinyl)-3-pyridinecarbonitrile, targets IκB kinases, with respective IC50 values of 8.5 and 250 nM for IKKβ and IKKα. ACHP’s selectivity is indicated by its > 20-μM IC50 values toward IKK3, Syk, and MAPKKK4. Inhibition of the TNFα-mediated gene expression could occur at low ACHP concentration (<1 μmol/L), with higher concentrations (>10 μmol/L) required to inhibit the constitutive phosphorylation of p65, expression of NF-κB-mediated genes (e.g., CYCLIN D1, BCL-xL, XIAP, c-IAP1, and IL-6), ultimately achieving myeloma cytostasis. Such findings indicate that ACHP’s growth inhibitory effects may be mediated through inhibition of both IKKα and IKKβ. By inhibiting NF-κB’s DNA binding activity, ACHP blocks the NF-κB pathway in multiple myeloma cell lines, inducing growth arrest and apoptosis.
IC 50
8.5 and 250 nm for ikkβ and ikkα, respectively
references
[1] sanda t, iida s, ogura h, asamitsu k, murata t, bacon kb, ueda r, okamoto t. growth inhibition of multiple myeloma cells by a novel ikappab kinase inhibitor. clin cancer res. 2005 mar 1;11(5):1974-82.
Check Digit Verification of cas no
The CAS Registry Mumber 406208-42-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 4,0,6,2,0 and 8 respectively; the second part has 2 digits, 4 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 406208-42:
(8*4)+(7*0)+(6*6)+(5*2)+(4*0)+(3*8)+(2*4)+(1*2)=112
112 % 10 = 2
So 406208-42-2 is a valid CAS Registry Number.
406208-42-2Relevant articles and documents
Synthesis and structure-activity relationships of novel IKK-β inhibitors. Part 3: Orally active anti-inflammatory agents
Murata, Toshiki,Shimada, Mitsuyuki,Sakakibara, Sachiko,Yoshino, Takashi,Masuda, Tsutomu,Shintani, Takuya,Sato, Hiroki,Koriyama, Yuji,Fukushima, Keiko,Nunami, Noriko,Yamauchi, Megumi,Fuchikami, Kinji,Komura, Hiroshi,Watanabe, Akihiko,Ziegelbauer, Karl B.,Bacon, Kevin B.,Lowinger, Timothy B.
, p. 4019 - 4022 (2007/10/03)
A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as IκB kinase β (IKK-β) inhibitors. Modification of a novel IKK-β inhibitor 1 (IKK-β IC 50=1500nM, Cell IC50=8000nM) at the 4-p
