1022958-60-6 Usage
Uses
CEP-28122 is used as an orally efficacious inhibitor of (ALK), analplastic lymphoma kinase, in the treatment of cancer.
Biological Activity
cep-28122, a highly potent, selective, orally bioavailable inhibitor of alk, dampens the phosphorylation of alk and alk substrates in cells and triggers cytotoxicity or growth inhibition of alk-positive cancer cells with a favorable pharmaceutical and pharmacokinetic profile and selective pharmacologic efficacy. cep-28122 blocks alk tyrosine phosphorylation in tumor xenografts in mice. alk, which is constitutively activated in many human cancer types because of point mutations, gene amplification, and chromosomal translocations, has emerged as an excellent molecular target for cancer therapy.
in vitro
cep-28122, concentration-dependently, triggered growth inhibition/cytotoxicity of alk-positive anaplastic large-cell lymphoma (alcl) via inhibiting nucleophosmin (npm) -alk tyrosine (664) phosphorylation. due to the cep-28122 treatment, eml4-alk tyrosine phosphorylation was blocked in non-small cell lung cancer (nsclc) nci-h2228 and nci-h3122 cells and full-length alk receptor tyrosine phosphorylation was inhibited in neuroblastoma cell line nb-1 cells [1].
in vivo
severe combined immunodeficient (scid) mice bearing sup-m2 (b) or nu/nu mice bearing colon carcinoma hct-116 (c) subcutaneous tumor xenografts were administered orally with cep-28122 at 3, 10, or 30 mg/kg for 24 days. cep-28122 showed inhibition of alk tyrosine phosphorylation in a dose-dependent manner in tumor xenografts in mice when treated at 30 mg/kg. moreover, cep-28122 displayed dose-dependent antitumor activity in alk-positive alcl, nsclc, and neuroblastoma tumor xenografts in mice when administered orally at 30 mg/kg or higher [1].
IC 50
1.9 nm: blocks anaplastic lymphoma kinase (alk).
references
[1]. cheng, m., quail, m., gingrich, d., ott, g., lu, l., & wan, w. et al. cep-28122, a highly potent and selective orally active inhibitor of anaplastic lymphoma kinase with antitumor activity in experimental models of human cancers. molecular cancer therapeutics. 2011; 11(3): 670-679.
Check Digit Verification of cas no
The CAS Registry Mumber 1022958-60-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,2,2,9,5 and 8 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1022958-60:
(9*1)+(8*0)+(7*2)+(6*2)+(5*9)+(4*5)+(3*8)+(2*6)+(1*0)=136
136 % 10 = 6
So 1022958-60-6 is a valid CAS Registry Number.
1022958-60-6Relevant articles and documents
Development and scale-up of an optimized route to the ALK inhibitor CEP-28122
Allwein, Shawn P.,Roemmele, Renee C.,Haley, James J.,Mowrey, Dale R.,Petrillo, Daniel E.,Reif, James J.,Gingrich, Diane E.,Bakale, Roger P.
, p. 148 - 155 (2012/05/20)
Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the
