Disease Information
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
Avapritinib
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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) | ||||
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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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) | ||||
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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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
Crenolanib
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
CHZ868
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
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
AZ960
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms | ||||
Aberration of the Drug's Therapeutic Target (ADTT) | ||||
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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