Drug Information

Drug (ID: DG01511) and It's Reported Resistant Information

• Name: Crenolanib
• Synonyms: Crenolanib; 670220-88-9; Crenolanib (CP-868596); CP-868596; ARO-002; UNII-LQF7I567TQ; CP-868,596; Crenolanib [USAN]; CP 868596; ARO 002; 1-(2-(5-((3-Methyloxetan-3-yl)methoxy)-1H-benzo-[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine; LQF7I567TQ; CP868569; 1-(2-{5-[(3-Methyloxetan-3-yl)methoxy]-1H-benzimidazol-1-yl}quinolin-8-yl)piperidin-4-amine; CP-868596 (Crenolanib); Crenolanib (USAN); MFCD21609260; 1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine; 1-[2-[5-[(3-Methyl-3-oxetanyl)methoxy]-1-benzimidazolyl]-8-quinolyl]-4-piperidinamine; 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine.; 1-(2-{5-[(3-methyloxetan-3-yl)methoxy]-1H-1,3-benzodiazol-1-yl}quinolin-8-yl)piperidin-4-amine; CP868596; Crenolanib [USAN:INN]; crenolanibum; 6T2; CP-868569; Crenolanib,CP-868596; [1-[2-[5-(3-Methyloxetan-3-ylmethoxy)benzimidazol-1-yl]quinolin-8-yl]piperidin-4-yl]amine; MLS006010956; Crenolanib - CP-868569; GTPL7882; SCHEMBL2730601; CHEMBL2105728; DTXSID50985873; EX-A215; CHEBI:145365; BDBM185149; HMS3656F19; AOB87312; BCP02384; ZINC3820043; NSC763526; NSC800079; s2730; AKOS026750597; BCP9000551; CCG-264988; CS-0566; DB11832; NSC-763526; NSC-800079; SB16603; NCGC00346658-01; NCGC00346658-09; 1-(2-(5-((3-methyloxetan-3-yl)methoxy)-1H-benzo[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine; AC-32071; AS-57698; HY-13223; SMR004702760; SY237889; FT-0665221; SW218293-2; X7517; D10102; J-502712; Q5184160; CP-868596;CP 868596;CP868596;ARO 002; 1-[2-[5-[(3-methyl-3-oxetanyl)methoxy]-1H-benzimidazol-1-yl]-8-quinolinyl]-4-piperidinamine; 1-{2-[5-(3-Methyl-oxetan-3-ylmethoxy)-benzoimidazol-1-yl]-quinolin-8-yl}-piperidin-4-ylamine
• Indication:
  In total 11 Indication(s)
  Advanced malignancy [ICD-11: 2A00-2F9Z]; Phase 3; [1]
  Colorectal cancer [ICD-11: 2B91]; Phase 3; [1]
  Gastrointestinal cancer [ICD-11: 2B5B]; Phase 3; [1]
  Haematological malignancy [ICD-11: 2B33]; Phase 3; [1]
  Hepatocellular carcinoma [ICD-11: 2C12]; Phase 3; [1]
  Pancreatic cancer [ICD-11: 2C10]; Phase 3; [1]
  Recurrent glioblastoma [ICD-11: 2A00]; Phase 3; [1]
  Recurring respiratory infection [ICD-11: CA07-CA4Z]; Phase 3; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 3; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 3; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Hematologic cancer [ICD-11: MG24]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [3]
• Target: Signal transducer and activator of transcription 3 (STAT3); STAT3_HUMAN; [4]
• Formula: 5
• IsoSMILES: CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
• InChI: InChI=1S/C26H29N5O2/c1-26(14-32-15-26)16-33-20-6-7-22-21(13-20)28-17-31(22)24-8-5-18-3-2-4-23(25(18)29-24)30-11-9-19(27)10-12-30/h2-8,13,17,19H,9-12,14-16,27H2,1H3
• InChIKey: DYNHJHQFHQTFTP-UHFFFAOYSA-N
• PubChem CID: 10366136
• ChEBI ID: CHEBI:145365
• TTD Drug ID: D01IGZ
• DrugBank ID: DB11832

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [3]

• Molecule Alteration: Missense mutation; p.Y288C (c.863A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay
• Mechanism Description: PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors, such as crenolanib, but sensitive to PI3K/mTOR and MEK inhibitors, such as omipalisib, consistent with pathway activation results.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [3]

• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BaF3 cells; Bone; Mus musculus (Mouse); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: XTT assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [3]

• Molecule Alteration: Missense mutation; p.V561D (c.1682T>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Presto blue assay

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.P577S (c.1729C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.P577S (c.1729C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.V658A (c.1973T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.V658A (c.1973T>C) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.R841K (c.2522G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.R841K (c.2522G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.D842Y (c.2524G>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.D842Y (c.2524G>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.H845Y (c.2533C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.H845Y (c.2533C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.G853D (c.2558G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.G853D (c.2558G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.N659K (c.1977C>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical assessment of PDGFRA/KIT kinase activity assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The missense mutation p.N659K (c.1977C>G) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Acute myeloid leukemia [ICD-11: 2A60]

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) [4]

• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: 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

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [6]

• Molecule Alteration: Missense mutation; p.D835H (c.2503G>C)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Colony assays; Plasma inhibitory assay

Hematologic cancer [ICD-11: 2B3Z]

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) [2]

• Molecule Alteration: Missense mutation; p.K429E (c.1285A>G)
• Resistant Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: 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) [2]

• Molecule Alteration: Missense mutation; p.Y572C (c.1715A>G)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: 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) [4]

• Molecule Alteration: Missense mutation; p.D835Y (c.2503G>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• 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
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: SKNO-1-luc cells; Bone marrow; Homo sapiens (Human); CVCL_2196
• In Vitro Model: MOLM14 cells; Peripheral blood; Homo sapiens (Human); CVCL_7916
• In Vitro Model: 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) [4]

• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: MV4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: 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

Gastrointestinal cancer [ICD-11: 2B5B]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Complex-indel; p.D842_I843delinsVM (c.2524_2529delinsGTAATG)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical assessment of PDGFRA/KIT kinase activity assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The complex-indel p.D842_I843delinsVM (c.2524_2529delinsGTAATG) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: IF-deletion; p.I843delI (c.2529_2531delCAT)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical assessment of PDGFRA/KIT kinase activity assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The if-deletion p.I843delI (c.2529_2531delCAT) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target.

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [7]

• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.D842Y (c.2524G>T)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical assessment of PDGFRA/KIT kinase activity assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The missense mutation p.D842Y (c.2524G>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [1]

• Molecule Alteration: Missense mutation; p.D842I (c.2524_2525delGAinsAT)
• Sensitive Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Biochemical assessment of PDGFRA/KIT kinase activity assay
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The missense mutation p.D842I (c.2524_2525delGAinsAT) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.P577S (c.1729C>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.P577S (c.1729C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.V658A (c.1973T>C)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.V658A (c.1973T>C) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.R841K (c.2522G>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.R841K (c.2522G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.H845Y (c.2533C>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.H845Y (c.2533C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.G853D (c.2558G>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.G853D (c.2558G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.P577S (c.1729C>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.P577S (c.1729C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.V658A (c.1973T>C)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.V658A (c.1973T>C) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.R841K (c.2522G>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.R841K (c.2522G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.H845Y (c.2533C>T)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.H845Y (c.2533C>T) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA) [5]

• Molecule Alteration: Missense mutation; p.G853D (c.2558G>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 293T cells; Breast; Homo sapiens (Human); CVCL_0063
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.G853D (c.2558G>A) in gene PDGFRA cause the sensitivity of Crenolanib by aberration of the drug's therapeutic target

References

• Ref 1: Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumorsClin Cancer Res. 2012 Aug 15;18(16):4375-84. doi: 10.1158/1078-0432.CCR-12-0625. Epub 2012 Jun 27.
• Ref 2: Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanismsNat Commun. 2019 Jan 16;10(1):244. doi: 10.1038/s41467-018-08263-x.
• Ref 3: Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapiesNat Commun. 2018 Nov 2;9(1):4583. doi: 10.1038/s41467-018-06949-w.
• Ref 4: Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignanciesBr J Haematol. 2019 Nov;187(4):488-501. doi: 10.1111/bjh.16092. Epub 2019 Jul 15.
• Ref 5: Large-scale analysis of PDGFRA mutations in melanomas and evaluation of their sensitivity to tyrosine kinase inhibitors imatinib and crenolanibClin Cancer Res. 2013 Dec 15;19(24):6935-42. doi: 10.1158/1078-0432.CCR-13-1266. Epub 2013 Oct 16.
• Ref 6: Crenolanib is a selective type I pan-FLT3 inhibitorProc Natl Acad Sci U S A. 2014 Apr 8;111(14):5319-24. doi: 10.1073/pnas.1320661111. Epub 2014 Mar 12.
• Ref 7: Dose escalating study of crenolanib besylate in advanced GIST patients with PDGFRA D842V activating mutations.