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Literature DB >> 32149729

Targeting AML-associated FLT3 mutations with a type I kinase inhibitor.

LaQuita M Jones¹, Katelyn Melgar^2,3, Lyndsey Bolanos², Kathleen Hueneman², Morgan M Walker⁴, Jian-Kang Jiang⁴, Kelli M Wilson⁴, Xiaohu Zhang⁴, Jian Shen⁵, Fan Jiang⁵, Patrick Sutter⁴, Amy Wang⁴, Xin Xu⁴, Gregory J Tawa⁴, Scott B Hoyt⁴, Mark Wunderlich², Eric O'Brien¹, John P Perentesis¹, Daniel T Starczynowski^2,6, Craig J Thomas^4,7.

Abstract

Tyrosine kinase domain (TKD) mutations contribute to acquired resistance to FMS-like tyrosine kinase 3 (FLT3) inhibitors used to treat FLT3-mutant acute myeloid leukemia (AML). We report a cocrystal structure of FLT3 with a type I inhibitor, NCGC1481, that retained potent binding and activity against FLT3 TKD and gatekeeper mutations. Relative to the current generation of advanced FLT3 inhibitors, NCGC1481 exhibited superior antileukemic activity against the common, clinically relevant FLT3-mutant AML cells in vitro and in vivo.

Entities: Chemical Disease Species

Keywords: Cancer; Drug therapy; Hematology; Leukemias; Oncology

Mesh：

Substances：

Year: 2020 PMID： 32149729 PMCID： PMC7108888 DOI： 10.1172/JCI127907

Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808

20 in total

1. Quizartinib tested in patients with high-risk AML.

Authors: Peter Sidaway
Journal: Nat Rev Clin Oncol Date: 2018-09 Impact factor: 66.675

2. Overcoming adaptive therapy resistance in AML by targeting immune response pathways.

Authors: Katelyn Melgar; Morgan M Walker; LaQuita M Jones; Lyndsey C Bolanos; Kathleen Hueneman; Mark Wunderlich; Jian-Kang Jiang; Kelli M Wilson; Xiaohu Zhang; Patrick Sutter; Amy Wang; Xin Xu; Kwangmin Choi; Gregory Tawa; Donald Lorimer; Jan Abendroth; Eric O'Brien; Scott B Hoyt; Ellin Berman; Christopher A Famulare; James C Mulloy; Ross L Levine; John P Perentesis; Craig J Thomas; Daniel T Starczynowski
Journal: Sci Transl Med Date: 2019-09-04 Impact factor: 17.956

3. How I treat FLT3-mutated AML.

Authors: Keith W Pratz; Mark Levis
Journal: Blood Date: 2016-11-21 Impact factor: 22.113

4. Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by single-cell analysis.

Authors: Catherine C Smith; Amy Paguirigan; Grace R Jeschke; Kimberly C Lin; Evan Massi; Theodore Tarver; Chen-Shan Chin; Saurabh Asthana; Adam Olshen; Kevin J Travers; Susana Wang; Mark J Levis; Alexander E Perl; Jerald P Radich; Neil P Shah
Journal: Blood Date: 2017-05-10 Impact factor: 22.113

Review 5. Secondary mutations as mediators of resistance to targeted therapy in leukemia.

Authors: Naval Daver; Jorge Cortes; Farhad Ravandi; Keyur P Patel; Jan A Burger; Marina Konopleva; Hagop Kantarjian
Journal: Blood Date: 2015-03-20 Impact factor: 22.113

Review 6. Midostaurin approved for FLT3-mutated AML.

Authors: Mark Levis
Journal: Blood Date: 2017-05-25 Impact factor: 22.113

7. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).

Authors: Patrick P Zarrinkar; Ruwanthi N Gunawardane; Merryl D Cramer; Michael F Gardner; Daniel Brigham; Barbara Belli; Mazen W Karaman; Keith W Pratz; Gabriel Pallares; Qi Chao; Kelly G Sprankle; Hitesh K Patel; Mark Levis; Robert C Armstrong; Joyce James; Shripad S Bhagwat
Journal: Blood Date: 2009-08-04 Impact factor: 22.113

Review 8. FLT3 Inhibitors in Acute Myeloid Leukemia: Current Status and Future Directions.

Authors: Maria Larrosa-Garcia; Maria R Baer
Journal: Mol Cancer Ther Date: 2017-06 Impact factor: 6.261

9. FLT3 D835 mutations confer differential resistance to type II FLT3 inhibitors.

Authors: C C Smith; K Lin; A Stecula; A Sali; N P Shah
Journal: Leukemia Date: 2015-06-25 Impact factor: 11.528

10. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms.

Authors: Kerstin Maria Kampa-Schittenhelm; Michael Charles Heinrich; Figen Akmut; Hartmut Döhner; Konstanze Döhner; Marcus Matthias Schittenhelm
Journal: Mol Cancer Date: 2013-03-07 Impact factor: 27.401

5 in total

Targeting AML-associated FLT3 mutations with a type I kinase inhibitor.

1. Quizartinib tested in patients with high-risk AML.

2. Overcoming adaptive therapy resistance in AML by targeting immune response pathways.

3. How I treat FLT3-mutated AML.

4. Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by single-cell analysis.

Review 5. Secondary mutations as mediators of resistance to targeted therapy in leukemia.

Review 6. Midostaurin approved for FLT3-mutated AML.

7. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).

Review 8. FLT3 Inhibitors in Acute Myeloid Leukemia: Current Status and Future Directions.

9. FLT3 D835 mutations confer differential resistance to type II FLT3 inhibitors.

10. Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms.

1. A new FLT3 inhibitor with two cases: the gilteritinib experience.

2. An Immune Checkpoint-Related Gene Signature for Predicting Survival of Pediatric Acute Myeloid Leukemia.

Review 3. IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.

Review 4. Genomic Abnormalities as Biomarkers and Therapeutic Targets in Acute Myeloid Leukemia.

Review 5. Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.