Journal: Leukemia

Article Title: Current status and future perspectives in targeted therapy of NPM1 -mutated AML

doi: 10.1038/s41375-022-01666-2

Figure Lengend Snippet: Clinical, pathological and molecular features of NPM1 -mutated AML.

Article Snippet: KO-539 , MOLM13, MV4-11, OCI-AML3 cell lines. AML primary patient samples with NPM1, KMT2A and FLT3-TKD mutations. PDX models with MLL-FP or NPM1 mutations. , NCT04067336 (KOMET-1) , Phase 1/2; 60 patients; Recruiting , FLT3 inhibitors , Evaluating efficacy.

Techniques: Biomarker Discovery, Expressing, Mutagenesis

Journal: Leukemia

Article Title: Current status and future perspectives in targeted therapy of NPM1 -mutated AML

doi: 10.1038/s41375-022-01666-2

Figure Lengend Snippet: Summary of in vitro and in vivo data of given compounds and related clinical trials.

Article Snippet: KO-539 , MOLM13, MV4-11, OCI-AML3 cell lines. AML primary patient samples with NPM1, KMT2A and FLT3-TKD mutations. PDX models with MLL-FP or NPM1 mutations. , NCT04067336 (KOMET-1) , Phase 1/2; 60 patients; Recruiting , FLT3 inhibitors , Evaluating efficacy.

Techniques: In Vitro, In Vivo, Inhibition

Journal: Leukemia

Article Title: Current status and future perspectives in targeted therapy of NPM1 -mutated AML

doi: 10.1038/s41375-022-01666-2

Figure Lengend Snippet: A Algorithm for the treatment of NPM1 -mutated AML patients older than 60 years. ^Based on the presence or absence of FLT3 mutations. CR complete remission, FLT3i FLT3 inhibitors, HMA hypomethylating agents, LDAC low-dose cytarabine, allo-HSCT allogeneic hematopoietic stem cell transplantation. B Examples of preemptive therapy with venetoclax as bridging to allo-HSCT. All three patients achieved molecular CR (negativity for NPM1 mutant transcripts) before allo-HSCT. VTX venetoclax, 5-AZA 5-azacytidine, CHT chemotherapy.

Article Snippet: KO-539 , MOLM13, MV4-11, OCI-AML3 cell lines. AML primary patient samples with NPM1, KMT2A and FLT3-TKD mutations. PDX models with MLL-FP or NPM1 mutations. , NCT04067336 (KOMET-1) , Phase 1/2; 60 patients; Recruiting , FLT3 inhibitors , Evaluating efficacy.

Techniques: Transplantation Assay, Mutagenesis

Journal: Frontiers in Immunology

Article Title: Analysis of Mononuclear Phagocytes Disclosed the Establishment Processes of Two Macrophage Subsets in the Adult Murine Kidney

doi: 10.3389/fimmu.2022.805420

Figure Lengend Snippet: Distinguishing macrophages from classical DCs in the kidney (A) Treating C57BL/6 mice with Flt3 inhibitor AC220 for 2 weeks significantly reduced the cell number of R6 cDC1s but had little impact on R1 cells. * P < 0.05; ns: not significant. P values were calculated using a two-tailed unpaired t-test. (B) Renal samples were stained with an anti-XCR1 antibody (dot line) or an isotype antibody (shaded). The R6 cells were examined (representative of n= 3 per group). (C) Zbtb46 expression was evaluated for renal mononuclear phagocyte subsets by GFP fluorescent intensity derived from Zbtb46 GFP /+ mice (representative of n= 3 per group). (D) Renal samples were stained with antibodies against the indicated markers (dot line) or related isotype control antibodies (shaded). The expression levels of the indicated markers on R7, R2, R4, R5 and R6 subsets are shown (representative of n=3 per group). Data are representative of at least two independent experiments. All error bars indicate mean ± SEM.

Article Snippet: FLT3 inhibitor AC220 (Adooq-bioscience) was administered to mice intragastrically in a dose of 10 mg/kg twice a day for two weeks.

Techniques: Two Tailed Test, Staining, Expressing, Derivative Assay, Control

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: Binding affinity of luxeptinib to wild type and mutant forms of FLT3

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques: Binding Assay, Mutagenesis

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: Potency of luxeptinib against key kinases

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques:

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: Antiproliferative potency of luxeptinib against malignant human myeloid lines

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques:

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: A, Growth inhibition curves for luxeptinib, quizartinib, gilteritinib and crenolanib against FLT3-mutant AML cell lines. B, Western blot analysis documenting concentration-dependent inhibition FLT3 and bypass pathways known to contribute to FLT3 inhibitor resistance (representative image from 3 biological repeats). C, Documentation of the ability of luxeptinib to kill FLT3-ITD cells as evidenced by induction of PARP cleavage.

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques: Inhibition, Mutagenesis, Western Blot, Concentration Assay

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: IC 50 in Ba/F3 cells transfect with FLT3 variants

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques:

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: Luxeptinib efficacy on subpopulations of AML patient samples according to ELN 2017 category (A) and type of disease (B). Horizontal line indicated median value; AUC is area under the concentration-survival curve. C, Heatmap depicting the effect of FLT3-ITD mutations on the IC50 values of luxeptinib and other FLT3 inhibitors tested against the same 186 patient samples; samples are grouped by FLT3 mutational status. D, Inhibitory effect of luxeptinib and venetoclax alone or in combination on bone marrow and peripheral blood samples from patients with AML (n=232) and MDS/MPN (n=34). One-way analysis of variance and Student’s t-test was used, ****, p<0.0001 and ns, not significant (p>0.05)

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques: Concentration Assay

Journal: Molecular cancer therapeutics

Article Title: Luxeptinib (CG-806) targets FLT3 and clusters of kinases operative in acute myeloid leukemia

doi: 10.1158/1535-7163.MCT-21-0832

Figure Lengend Snippet: A, Impact of FLT3 and NPM1 mutations on sensitivity to luxeptinib as measured by area under the concentration-survival curve. B, Analysis of the effect of FLT3-ITD allelic ratio and NPM1 mutation on sensitivity to luxeptinib. C – E, Effect of mutations in ASXL1, TP53, IDH1, IDH2, and SRSF2 on IC50. F and G, distribution of IC50 values for luxeptinib, gilteritinib, quizartinib and midostaurin in samples with wild type (F) or mutant NRAS (G). Horizontal bar indicates median. Student’s t-test was used, ****, p<0.0001 ***, p<0.001, *, p<0.05 and ns, not significant (p>0.05)

Article Snippet: FLT3 inhibitors gilteritinib, quizartinib, crenolanib and midostaurin were purchased from Chemietek, Selleck Chemical, Cayman Chemical and Sigma Aldrich, respectively.

Techniques: Concentration Assay, Mutagenesis

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Chemical structures of Sunitinib, Quizartinib, Sorafenib, Midostaurin, and Lestaurtinib.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Quizartinib into the Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3) interaction site. ( A ) The structure with yellow carbon atoms is the redocked Quizartinib. ( B ) Hydrogen bonds provide evidence for redocked Quizartinib and amino acid residues are located at a distance of 5Å.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Chemical structures, IC 50 and pIC 50 values of 1 – 41 [ 11 ], Quizartinib and Sunitinib FLT3 inhibitor compounds. Test set compounds are marked with an asterisk.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Overlapped conformations of FLT3 inhibitors. Quizartinib is shown in yellow, and Sunitinib is shown in purple.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Overlapped conformations of compound 1 , Quizartinib (yellow), and Sunitinib (purple).

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Chemical structures, predicted pIC 50 values, MolDock Scores (kcal mol −1 ), pose-protein interaction (kcal mol −1 ) and hydrogen bond interactions (kcal mol −1 ) for the most promising derivatives against FLT3.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Chemical structure, predicted pIC 50 , MolDock Scores (kcal mol −1 ) of ligand-protein interactions (kcal mol −1 ) and hydrogen bond interactions (kcal mol −1 ) for a promising dual Aurora B/FLT3 inhibitor.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques:

Journal: Molecules

Article Title: Theoretical Studies Aimed at Finding FLT3 Inhibitors and a Promising Compound and Molecular Pattern with Dual Aurora B/FLT3 Activity

doi: 10.3390/molecules25071726

Figure Lengend Snippet: Promising indolin−2-one molecular pattern for dual Aurora B/FLT3 activity.

Article Snippet: Compounds 1 – 45 [ ], Quizartinib, and Sunitinib FLT3 inhibitor ( ) were docked into the FLT3 kinase domain using the Molegro Virtual Docker (MVD) [ , , ].

Techniques: Activity Assay

Journal: Frontiers in Chemistry

Article Title: Urea-based anticancer agents. Exploring 100-years of research with an eye to the future

doi: 10.3389/fchem.2022.995351

Figure Lengend Snippet: Summary of cited patents.

Article Snippet: TW201706256A , Sunshine Lake Pharma , 2017 , FLT3 Inhibitors , Preclinical phase.

Techniques: