Pyr1
Names | |
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Preferred IUPAC name
5,11-Dimethyl-1-oxo-2,6-dihydro-1H-pyrido[4,3-b]carbazol-9-yl benzoate | |
Other names
LIMINIB
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Identifiers | |
3D model (
JSmol ) |
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ChemSpider | |
PubChem CID
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UNII | |
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Properties | |
C24H18N2O3 | |
Molar mass | 382.419 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Pyr1 (LIMINIB) is an
It was discovered by the Cure and
Pyr1 reversibly stabilizes
Description and properties
Pyr1 is classified as a small molecule that belongs to the group of pyridocarbazoles.[2] Its small size gives it special properties: as a light molecule it is a valuable tool for studying dynamic biological processes. Therefore, it is a key discovery in medical and biological investigation. It is a high degree protein temporal controller, as it is able to interact in a few minutes or even seconds with molecules such as LIMK1. Its reversibility enables it to quickly activate and inhibit itself, making the molecule a specific inhibitor both in vitro and in cellulo.
Pyr1 can be described as a tetracyclic molecule with a simple structure. Its few radicals are widely expanded along the
Mechanism of action
Pyr 1 is a cell permeable competitive inhibitor of Lim Kinase (especially LIMK1). The latter is the enzyme that uses ATP to phosphorylate and inactivate the actin-depolymerizing factor
In the presence of Pyr1, LIMK1 is inhibited, which means that the phosphorylation of cofilin decreases, which results in the blockage of the regulation of actin microfilaments dynamics and, therefore, the disorganization of microfilaments. It also causes the stabilization of microtubules. This inhibition is reversible.
In conclusion, Pyr1 inhibits cell motility and controls actin dynamics and stabilizes microtubules. These properties can be used in anticancer treatment.
Medical applications
Cancer metastasis consists in the fast and uncontrolled division of abnormal cells. Microtubules have a key role in
These anticancer drugs have, however, some limitations due to side effects, principally
Pyr1 may be used in cancer treatment, because its main target enzyme (LIM kinase) is a regulator of microtubule and actin dynamics. Moreover, it has been shown that Pyr1 is toxic for cancerous cell lines, even the ones that are resistant to conventional microtubule targeting agents.
Furthermore, the toxicity of Pyr1 has been studied in mice, to evaluate whether it could really work as a chemotherapeutic agent. The results show a complete survival of mice against
Bearing the previous points in mind, Pyr1 may be used in addition or as an alternative to standard chemotherapy in drug resistant tumors.
References
- PMID 22761334.
- ^ Pyridocarbazoles