Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family.
The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2017
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| _version_ | 1826280632513200128 |
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| author | Bataille, C Brennan, M Byrne, S Davies, S Durbin, M Fedorov, O Huber, K Jones, A Knapp, S Liu, G Nadali, A Quevedo, C Russell, A Walker, R Westwood, R Wynne, G |
| author_facet | Bataille, C Brennan, M Byrne, S Davies, S Durbin, M Fedorov, O Huber, K Jones, A Knapp, S Liu, G Nadali, A Quevedo, C Russell, A Walker, R Westwood, R Wynne, G |
| author_sort | Bataille, C |
| collection | OXFORD |
| description | The PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC50 of 0.75μM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition. |
| first_indexed | 2024-03-07T00:16:37Z |
| format | Journal article |
| id | oxford-uuid:7b0cdcdc-22cb-46f9-9a3a-f3e33a8b468d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:16:37Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:7b0cdcdc-22cb-46f9-9a3a-f3e33a8b468d2022-03-26T20:48:19ZThiazolidine derivatives as potent and selective inhibitors of the PIM kinase family.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7b0cdcdc-22cb-46f9-9a3a-f3e33a8b468dEnglishSymplectic Elements at OxfordElsevier2017Bataille, CBrennan, MByrne, SDavies, SDurbin, MFedorov, OHuber, KJones, AKnapp, SLiu, GNadali, AQuevedo, CRussell, AWalker, RWestwood, RWynne, GThe PIM family of serine/threonine kinases have become an attractive target for anti-cancer drug development, particularly for certain hematological malignancies. Here, we describe the discovery of a series of inhibitors of the PIM kinase family using a high throughput screening strategy. Through a combination of molecular modeling and optimization studies, the intrinsic potencies and molecular properties of this series of compounds was significantly improved. An excellent pan-PIM isoform inhibition profile was observed across the series, while optimized examples show good selectivity over other kinases. Two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, were employed to evaluate the in vitro anti-proliferative effects of selected inhibitors. Encouraging activities were observed for many examples, with the best example (44) giving an IC50 of 0.75μM against the K562 cell line. These data provide a promising starting point for further development of this series as a new cancer therapy through PIM kinase inhibition. |
| spellingShingle | Bataille, C Brennan, M Byrne, S Davies, S Durbin, M Fedorov, O Huber, K Jones, A Knapp, S Liu, G Nadali, A Quevedo, C Russell, A Walker, R Westwood, R Wynne, G Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. |
| title | Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. |
| title_full | Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. |
| title_fullStr | Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. |
| title_full_unstemmed | Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. |
| title_short | Thiazolidine derivatives as potent and selective inhibitors of the PIM kinase family. |
| title_sort | thiazolidine derivatives as potent and selective inhibitors of the pim kinase family |
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