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Abstract
Discussion Forum (0)
Poster Category: NIA Award Recipient Abstract
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
Poster Category: NIA Award Recipient Abstract
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
Development of Chemical Affinity Probe for Quantitative Proteomic Profiling of PI3Ks
Xin Chen
Abstract
Discussion Forum (0)
Poster Category: NIA Award Recipient Abstract
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
Poster Category: NIA Award Recipient Abstract
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
AACP Section:
Objectives: To develop chemical affinity probes that can be immobilized on Sepharose beads and can be used to quantify wild-type and mutant PI3Ks from cancer cell lines and PDXs.
Methods: The new chemical affinity probes for PI3Ks were designed and synthesized based on the structure of pan-PI3K inhibitor NVP-BKM120 and their inhibitory activities against PI3Ks were evaluated in vitro. Then the selected newly developed PI3K chemical affinity probe was immobilized onto the Sepharose beads to test its capacity of quantifying wide-type and mutant PI3Ks from a variety of tumor cell lines and patient derived xenografts following the established MIB-MS protocol.
Results: The newly developed PI3K chemical affinity probe had similar activity towards PI3Ks and other kinases as BKM120. The novel PI3K inhibitor beads could capture PI3Ks and their regulatory subunits from a variety of breast cancer cell lines and PDXs. It exhibited competitive capture of PI3Ks from SKBR3 cells with IC50 values calculated from dose-dependent curves for BYL719 and BKM120 comparable to the published values. It also demonstrated capacity to capture PIK3CA H1047R mutant form in bioengineered SKBR3 cells harboring H1047R mutant and from A375 mutated cell with H1047R mutant.
Conclusion: While PI3K pathway is frequently hyper activated and/or mutated in human cancers, resulting in the resistance to anti-cancer agents, we have developed a chemical affinity probe for quantitative proteomic profiling of wide type and mutant PI3Ks. The new PI3K inhibitor beads not only can expand the kinome coverage of MIB-MS, but also can help analyze the dynamic changes of PI3Ks in various cancers and identify possible binding partners for desired/undesired biological effects. The results obtained may also provide guidance in formulating precision medicine for cancer patients.
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