General Information of the Disease (ID: DIS00367)
Name
Hematologic cancer
ICD
ICD-11: 2B3Z
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
6 drug(s) in total
Click to Show/Hide the Full List of Drugs
Avapritinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D835Y (c.2503G>T)
Resistant Drug Avapritinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D816V (c.2447A>T)
Sensitive Drug Avapritinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
Fedratinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R867Q (c.2600G>A)
Resistant Drug Fedratinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
WST-1 cell proliferation assay
Gilteritinib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D835Y (c.2503G>T)
Sensitive Drug Gilteritinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D816V (c.2447A>T)
Sensitive Drug Gilteritinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
Midostaurin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D835Y (c.2503G>T)
Sensitive Drug Midostaurin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D816V (c.2447A>T)
Sensitive Drug Midostaurin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
Ruxolitinib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R867Q (c.2600G>A)
Resistant Drug Ruxolitinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
WST-1 cell proliferation assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Calreticulin (CALR) [3]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration FS-insertion
p.K385fs*47 (c.1153_1154insTAATT)
Sensitive Drug Ruxolitinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay
Tofacitinib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [4]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.M511I (c.1533G>C)
Sensitive Drug Tofacitinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTS assay; FACS assay
Mechanism Description Jak3 inhibitors CP-690,550 and NC1153 showed efficacy in reducing viability of Ba/F3 cells transformed with mutant forms of Jak3.
Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [4]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.A573V (c.1718C>T)
Sensitive Drug Tofacitinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTS assay; FACS assay
Mechanism Description Jak3 inhibitors CP-690,550 and NC1153 showed efficacy in reducing viability of Ba/F3 cells transformed with mutant forms of Jak3.
Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [5]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.H583Y (c.1747C>T)
Sensitive Drug Tofacitinib
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation JAKT/STAT signaling pathway Inhibition hsa04630
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
Experiment for
Molecule Alteration
Immunohistochemistry assay; Immunoblotting assay
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description A STAT3 inhibitor was active against STAT3 -mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3 - or STAT3 -mutant NTCL.
Key Molecule: Tyrosine-protein kinase JAK3 (JAK3) [5]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.G589D (c.1766G>A)
Sensitive Drug Tofacitinib
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation JAKT/STAT signaling pathway Inhibition hsa04630
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
NIH-3T3 cells Embryo Mus musculus (Mouse) CVCL_0594
Experiment for
Molecule Alteration
Immunohistochemistry assay; Immunoblotting assay
Experiment for
Drug Resistance
CCK-8 assay
Mechanism Description A STAT3 inhibitor was active against STAT3 -mutant SNK-6 and YT cells. Novel JAK3 mutations are oncogenic and druggable in NTCL. The JAK3 or STAT3 signal was altered in NTCL, and pathway inhibition might be a therapeutic option for patients with JAK3 - or STAT3 -mutant NTCL.
Clinical Trial Drug(s)
8 drug(s) in total
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Crenolanib
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [6]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.K429E (c.1285A>G)
Resistant Drug Crenolanib
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Whole exome sequencing
Experiment for
Drug Resistance
MTS assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [6]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.Y572C (c.1715A>G)
Sensitive Drug Crenolanib
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Whole exome sequencing
Experiment for
Drug Resistance
MTS assay
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D835Y (c.2503G>T)
Sensitive Drug Crenolanib
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
SKNO-1-luc cells Bone marrow Homo sapiens (Human) CVCL_2196
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
Kasumi-1-luc cells N.A. . N.A.
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Trypan blue exclusion assay
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D816V (c.2447A>T)
Sensitive Drug Crenolanib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
MOLM14 cells Peripheral blood Homo sapiens (Human) CVCL_7916
In Vivo Model Female NCr-nude mouse model Mus musculus
Experiment for
Drug Resistance
CellTiter-Glo assay; IC50 assay
Enasidenib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [7]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R140K (c.418_419delCGinsAA)
Sensitive Drug Enasidenib
Experimental Note Identified from the Human Clinical Data
Key Molecule: Isocitrate dehydrogenase NADP 2 (IDH2) [7]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R172K (c.515G>A)
Sensitive Drug Enasidenib
Experimental Note Identified from the Human Clinical Data
Momelotinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R867Q (c.2600G>A)
Resistant Drug Momelotinib
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
WST-1 cell proliferation assay
AUY922
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R867Q (c.2600G>A)
Resistant Drug AUY922
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
WST-1 cell proliferation assay
BMS-911543
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [8]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.V617F (c.1849G>T)
Sensitive Drug BMS-911543
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
[3H] thymidine incorporation assay
Mechanism Description The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of BMS-911543 by aberration of the drug's therapeutic target
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Thrombopoietin receptor (TPOR) [8]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.W515L (c.1544G>T)
Sensitive Drug BMS-911543
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
[3H] thymidine incorporation assay
Mechanism Description The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of BMS-911543 by unusual activation of pro-survival pathway
FF-10101
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [9]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D816V (c.2447A>T)
Sensitive Drug FF-10101
Experimental Note Identified from the Human Clinical Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
In Vivo Model NOD/SCID mouse PDX model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Colony formation assay
NS-018
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [10]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.V617F (c.1849G>T)
Sensitive Drug NS-018
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Sf9 cells Ovary Homo sapiens (Human) CVCL_0549
Experiment for
Molecule Alteration
Colony formation assay
Experiment for
Drug Resistance
MTT assay
Mechanism Description The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of NS-018 by aberration of the drug's therapeutic target
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Thrombopoietin receptor (TPOR) [10]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.W515L (c.1544G>T)
Sensitive Drug NS-018
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Sf9 cells Ovary Homo sapiens (Human) CVCL_0549
Experiment for
Molecule Alteration
Colony formation assay
Experiment for
Drug Resistance
MTT assay
Mechanism Description The missense mutation p.W515L (c.1544G>T) in gene MPL cause the sensitivity of NS-018 by unusual activation of pro-survival pathway
LY3009120
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [11]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.K601N (c.1803A>C)
Sensitive Drug LY3009120
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
OV-90 cells Ascites Homo sapiens (Human) CVCL_3768
H2405 cells Lung Homo sapiens (Human) CVCL_1551
In Vivo Model NIH nude rat xenograft model Rattus norvegicus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
Preclinical Drug(s)
5 drug(s) in total
Click to Show/Hide the Full List of Drugs
CHZ868
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Thrombopoietin receptor (TPOR) [12]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.W515L (c.1544G>T)
Sensitive Drug CHZ868
Experimental Note Identified from the Human Clinical Data
In Vitro Model TF-1 cells Bone marrow Homo sapiens (Human) CVCL_0559
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
W515L cells Blood Homo sapiens (Human) N.A.
SET2 cells Peripheral blood Homo sapiens (Human) CVCL_2187
In Vivo Model CD45.2 Jak2V617F mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell viability luminescent assay
Crenolanib/Trametinib
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [6]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D835Y (c.2503G>T)
Sensitive Drug Crenolanib/Trametinib
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
HEK 293T cells Kidney Homo sapiens (Human) CVCL_0063
Experiment for
Molecule Alteration
Whole exome sequencing
Experiment for
Drug Resistance
MTS assay
E7107
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Splicing factor 3B subunit 1 (SF3B1) [13]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.K700E (c.2098A>G)
Sensitive Drug E7107
Experimental Note Identified from the Human Clinical Data
II-B08
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [14]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.E76K (c.226G>A)
Sensitive Drug II-B08
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
3H-thymidine incorporation assay
Mechanism Description The missense mutation p.E76K (c.226G>A) in gene PTPN11 cause the sensitivity of II-B08 by unusual activation of pro-survival pathway
SHP099
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [15]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.V617F (c.1849G>T)
Sensitive Drug SHP099
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation RAS/ERK signaling pathway Inhibition hsa01521
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
NCI-H2228 cells Lung Homo sapiens (Human) CVCL_1543
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
A2058 cells Skin Homo sapiens (Human) CVCL_1059
KYSE520 cells Esophagus Homo sapiens (Human) CVCL_1355
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
Sum52 cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H2170 cells Lung Homo sapiens (Human) CVCL_1535
NCI-H2170 cells Lung Homo sapiens (Human) CVCL_1535
H293 cells Kidney Homo sapiens (Human) N.A.
In Vivo Model Athymic nude mouse PDX model Mus musculus
Experiment for
Drug Resistance
CellTitre-Glo assay; Crystal violet staining assay
Mechanism Description SHP099 suppresses RAS-ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models.
Investigative Drug(s)
2 drug(s) in total
Click to Show/Hide the Full List of Drugs
AZ960
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]
Resistant Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.R867Q (c.2600G>A)
Resistant Drug AZ960
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
WST-1 cell proliferation assay
G-749
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [16]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Molecule Alteration Missense mutation
p.D835Y (c.2503G>T)
Sensitive Drug G-749
Experimental Note Identified from the Human Clinical Data
In Vitro Model KG1a cells Pleural effusion Homo sapiens (Human) CVCL_1824
Kasumi-1 cells Peripheral blood Homo sapiens (Human) CVCL_0589
MOLM-13 cells Peripheral blood Homo sapiens (Human) CVCL_2119
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
Experiment for
Molecule Alteration
Kinase inhibition assessment assay
Experiment for
Drug Resistance
Fluorometric microculture cytotoxicity assay
Mechanism Description The missense mutation p.D835Y (c.2503G>T) in gene FLT3 cause the sensitivity of G-749 by aberration of the drug's therapeutic target
References
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Ref 2 Germ-line JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitorsBlood. 2014 Feb 27;123(9):1372-83. doi: 10.1182/blood-2013-05-504555. Epub 2014 Jan 7.
Ref 3 Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutantsBlood. 2016 Mar 10;127(10):1325-35. doi: 10.1182/blood-2015-11-681932. Epub 2015 Dec 14.
Ref 4 Transforming Mutations of Jak3 (A573V and M511I) Show Differential Sensitivity to Selective Jak3 InhibitorsClin Cancer Drugs. 2016;3(2):131-137. doi: 10.2174/2212697X03666160610085943.
Ref 5 Novel JAK3-Activating Mutations in Extranodal NK/T-Cell Lymphoma, Nasal TypeAm J Pathol. 2017 May;187(5):980-986. doi: 10.1016/j.ajpath.2017.01.004. Epub 2017 Mar 9.
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Ref 7 Abstract CT103: Clinical safety and efficacy of pembrolizumab (MK-3475) in patients with malignant pleural mesothelioma: Preliminary results from KEYNOTE-0280.
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Ref 9 A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against AML cells with FLT3 mutationsBlood. 2018 Jan 25;131(4):426-438. doi: 10.1182/blood-2017-05-786657. Epub 2017 Nov 29.
Ref 10 Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasmsBlood Cancer J. 2011 Jul;1(7):e29. doi: 10.1038/bcj.2011.29. Epub 2011 Jul 22.
Ref 11 Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120Cancer Discov. 2016 Mar;6(3):300-15. doi: 10.1158/2159-8290.CD-15-0896. Epub 2016 Jan 5.
Ref 12 CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative NeoplasmsCancer Cell. 2015 Jul 13;28(1):15-28. doi: 10.1016/j.ccell.2015.06.006.
Ref 13 Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome ModulationCancer Cell. 2016 Sep 12;30(3):404-417. doi: 10.1016/j.ccell.2016.08.006.
Ref 14 Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)J Med Chem. 2010 Mar 25;53(6):2482-93. doi: 10.1021/jm901645u.
Ref 15 Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinasesNature. 2016 Jul 7;535(7610):148-52. doi: 10.1038/nature18621. Epub 2016 Jun 29.
Ref 16 The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemiaBlood Cancer J. 2012 Aug 3;2(8):e81. doi: 10.1038/bcj.2012.28.

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