α‐Aminophosphonates as Potential PARP1 Inhibitors

Stephanie S Schweiker; Amanda L Tauber; Caleb Kam; Daniel J. Eyckens; Luke Henderson; Stephan M Levonis

doi:10.1002/slct.202000520

α‐Aminophosphonates as Potential PARP1 Inhibitors

Stephanie S Schweiker^*, Amanda L Tauber, Caleb Kam, Daniel J. Eyckens, Luke Henderson, Stephan M Levonis

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

ADP‐ribosyl transferase member 1 (PARP1) is primarily known for its involvement in signaling DNA damage repair mechanisms within a cell. PARP1 inhibitors are used currently for the management of breast cancer (BRCA) gene mutated breast and ovarian cancers. These current generation PARP1 inhibitors are non‐selective for PARP1, over the PARP superfamily enzymes. Here we report on a novel class of PARP1 inhibitors, the α‐aminophosphonates. α‐Αminophosphonates 1–23 were screened in silico for their binding interactions and tested for inhibitory activity against PARP1. α‐Aminophosphonates 17 and 20 were identified as the most effective PARP1 inhibitors. They inhibited PARP1’s activity, at 10 μM, by 63±3% and 56±3%, respectively.

Original language	English
Pages (from-to)	4205-4209
Number of pages	5
Journal	Chemistry Select
Volume	5
Issue number	14
DOIs	https://doi.org/10.1002/slct.202000520
Publication status	Published - 16 Apr 2020

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α‐Aminophosphonates as Potential PARP1 InhibitorsAccepted author manuscript, 286 KBLicence: Other

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abstract = "ADP‐ribosyl transferase member 1 (PARP1) is primarily known for its involvement in signaling DNA damage repair mechanisms within a cell. PARP1 inhibitors are used currently for the management of breast cancer (BRCA) gene mutated breast and ovarian cancers. These current generation PARP1 inhibitors are non‐selective for PARP1, over the PARP superfamily enzymes. Here we report on a novel class of PARP1 inhibitors, the α‐aminophosphonates. α‐Αminophosphonates 1–23 were screened in silico for their binding interactions and tested for inhibitory activity against PARP1. α‐Aminophosphonates 17 and 20 were identified as the most effective PARP1 inhibitors. They inhibited PARP1{\textquoteright}s activity, at 10 μM, by 63±3% and 56±3%, respectively.",

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AU - Schweiker, Stephanie S

AU - Tauber, Amanda L

AU - Kam, Caleb

AU - Eyckens, Daniel J.

AU - Henderson, Luke

AU - Levonis, Stephan M

PY - 2020/4/16

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AB - ADP‐ribosyl transferase member 1 (PARP1) is primarily known for its involvement in signaling DNA damage repair mechanisms within a cell. PARP1 inhibitors are used currently for the management of breast cancer (BRCA) gene mutated breast and ovarian cancers. These current generation PARP1 inhibitors are non‐selective for PARP1, over the PARP superfamily enzymes. Here we report on a novel class of PARP1 inhibitors, the α‐aminophosphonates. α‐Αminophosphonates 1–23 were screened in silico for their binding interactions and tested for inhibitory activity against PARP1. α‐Aminophosphonates 17 and 20 were identified as the most effective PARP1 inhibitors. They inhibited PARP1’s activity, at 10 μM, by 63±3% and 56±3%, respectively.

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α‐Aminophosphonates as Potential PARP1 Inhibitors

Abstract

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