300815-04-7 Usage
Uses
Used in Cancer Research and Treatment:
Apcin is used as an inhibitor of the APC/C for blocking mitotic exit, which can be beneficial in the study and treatment of cancer. Its ability to halt the cell cycle at the mitotic stage may provide valuable insights into the mechanisms of cancer cell division and contribute to the development of targeted cancer therapies.
Additionally, Apcin's synergistic effect when co-administered with Ts-Arg-OMe suggests that it could be used in combination therapies to enhance the efficacy of existing treatments and potentially overcome drug resistance in cancer cells.
Used in Drug Delivery Systems:
Similar to gallotannin, Apcin could also be incorporated into novel drug delivery systems to improve its delivery, bioavailability, and therapeutic outcomes. By employing various organic and metallic nanoparticles as carriers, the limitations of Apcin could be overcome, leading to more effective cancer treatments.
Biochem/physiol Actions
Apcin is an inhibitor of the anaphase-promoting complex/cyclosome (APC/C), a large multimeric complex that functions as a ubiquitin ligase, initiating the metaphase–anaphase transition and regulating ordered transitions through the cell cycle by controlling the ubiquitin-mediated proteolysis of cell cycle proteins. Apcin prevents substrate recognition and inhibits APC/C-dependent ubiquitylation by binding to the D-box binding site of Cdc20, a coactivator required for full activation of APC/C and substrate recognition. The effectiveness of apcin in blocking mitotic exit was synergistically amplified by co-addition of TAME (tosyl-L-arginine methyl ester) or its cell permeable prodrug proTAME, which block Cdc20 binding to the APC/C at a different site than apcin.
Enzyme inhibitor
This Cdc20 inhibitor (FW = 438.65 g/mol; CAS 300815-04-7; Solubility: 100 mM in DMSO), also named 3-(2-methyl-5-nitroimidazol-1-yl)-N- (2,2,2-trichloro-1-phenylaminoethyl)propionamide, targets substrate interaction of Cell division control protein 20, blocking substrate-mediated Cdc20 loading onto the Anaphase-Promoting Complex. APC is a 13- subunit ubiquitin ligase that initiates the metaphase-anaphase transition and mitotic exit by targeting proteins such as securin and cyclin B1 for ubiquitin-dependent destruction by the proteasome. APC regulates cell cycle progression by forming APC·Cdc20 and APC·Cdh1, two closely related, but functionally distinct, E3 ubiquitin ligase sub-complexes. Cdh1 and Cdc20 have opposing functions in tumorigenesis, with the former largely functioning as a tumor suppressor, and the latter exhibiting an oncogenic function. Because blocking mitotic exit is an effective approach for inducing tumour cell death, the APC/C represents a potential novel target for cancer therapy. APC/C activation during mitosis requires Cdc20binding, forming a co-receptor with the APC/C to recognize substrates containing a destruction box (D-box). APC/C-dependent proteolysis and mitotic exit can be synergistically inhibited by simultaneously disrupting two protein-protein interactions within the APC/C-Cdc20-substrate ternary complex. APC inhibitor, or Apcin, binds to Cdc20, competitively inhibiting ubiquitylation of D-box-containing substrates. Analysis of the crystal structure of the apcin-Cdc20 complex suggests that apcin occupies the D-box-binding pocket on the side face of the WD40-domain. The ability of Apcin to block mitotic exit is enhanced by co-addition of tosyl-l-arginine methyl ester (See TAME), a small molecule that blocks the APC/C-Cdc20 interaction. Apcin also inhibits APC-dependent ubiquitylation and prolongs mitotic duration in RPE1 cells, when administered in combination with proTAME, a prodrug of TAME in vitro (See pro-TAME).
Check Digit Verification of cas no
The CAS Registry Mumber 300815-04-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,0,0,8,1 and 5 respectively; the second part has 2 digits, 0 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 300815-04:
(8*3)+(7*0)+(6*0)+(5*8)+(4*1)+(3*5)+(2*0)+(1*4)=87
87 % 10 = 7
So 300815-04-7 is a valid CAS Registry Number.
300815-04-7Relevant academic research and scientific papers
Huang, Pan,Le, Xiangyang,Huang, Fei,Yang, Jie,Yang, Haofeng,Ma, Junlong,Hu, Gaoyun,Li, Qianbin,Chen, Zhuo
, p. 4685 - 4700 (2020)
Apcin is one of the few compounds that have been previously reported as a Cdc20 specific inhibitor, although Cdc20 is a very promising drug target. We reported here the design, synthesis, and biological evaluations of 2,2,2-trichloro-1-aryl carbamate derivatives as Cdc20 inhibitors. Among these derivatives, compound 9f was much more efficient than the positive compound apcin in inhibiting cancer cell growth, but it had approximately the same binding affinity with apcin in SPR assays. It is possible that another mechanism of action might exist. Further evidence demonstrated that compound 9f also inhibited tubulin polymerization, disorganized the microtubule network, and blocked the cell cycle at the M phase with changes in the expression of cyclins. Thus, it induced apoptosis through the activation of caspase-3 and PARP. In addition, compound 9f inhibited cell migration and invasion in a concentration-dependent manner. These results provide guidance for developing the current series as potential new anticancer therapeutics.
