57046-73-8 Usage
Description
Paprotrain, PAssenger PROteins TRAnsport INhibitor, is a cell-permeable, reversible inhibitor of the mitotic kinesin-like protein 2 (MKLP-2), an N-terminal motor from the kinesin-6 family. It is uncompetitive with ATP (Ki = 3.4 μM) and noncompetitive with microtubules (Ki = 1.6 μM), demonstrating ATPase inhibition of basal and microtubule-stimulated activities with IC50 values of 1.35 and 0.83 μM, respectively. Paprotrain does not inhibit twelve additional kinesins, including the closely related kinesin-6 motors MKLP-1 and MPP1. Incubation with 10-50 μM paprotrain results in binucleated cells, perturbing relocation of Aurora B kinase and survivin without affecting microtubule polymerization.
Uses
Used in Cell Biology Research:
Paprotrain is used as a cell-permeable inhibitor of the kinesin-6 family member KIF20A (MKLP-2) for studying the role of MKLP-2 in normal cleavage furrow ingression and cytokinesis. It helps in understanding the relocation of chromosome passenger proteins Aurora B kinase and survivin from the centromeres to the central spindle in anaphase cells, facilitating cytokinesis and avoiding the generation of binucleated cells.
Used in Drug Development:
Paprotrain can be used as a potential therapeutic agent in the development of drugs targeting the kinesin-6 family, specifically MKLP-2, for the treatment of diseases related to abnormal cell division and cytokinesis.
Check Digit Verification of cas no
The CAS Registry Mumber 57046-73-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,0,4 and 6 respectively; the second part has 2 digits, 7 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 57046-73:
(7*5)+(6*7)+(5*0)+(4*4)+(3*6)+(2*7)+(1*3)=128
128 % 10 = 8
So 57046-73-8 is a valid CAS Registry Number.
57046-73-8Relevant articles and documents
Discovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131)
See, Cheng Shang,Kitagawa, Mayumi,Liao, Pei-Ju,Lee, Kyung Hee,Wong, Jasmine,Lee, Sang Hyun,Dymock, Brian W.
, p. 344 - 367 (2018/07/25)
Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy. Compound 4a was first identified in a phenotypic screen in which HeLa cells treated with 4a manifested mitotic arrest along with formation of multiple vesicles. Further investigations showed that 4a causes an increase in mitotic marker pH3 and autophagy marker LC3. Importantly 4a induces cell death in cancer cells while sparing normal cells which regrow after 4a is removed. Dual activities against pH3 and LC3 markers are required for cancer cell selectivity. An extensive SAR investigation confirmed 4a as the optimal dual inhibitor with potency against a panel of 30 cancer cell lines (average antiproliferative GI50 1.5 μM). In a mouse model of paclitaxel-resistant colon cancer, 4a showed 74% tumor growth inhibition when administered at a dose of 20 mg/kg IP twice a day.
Use of derivatives of indoles for the treatment of cancer
-
, (2011/01/12)
The present invention relates to the use of derivatives of indoles having a general formula (I) as follow: for the manufacture of a pharmaceutical composition intended for the treatment of cancer.
