Drug Information

Drug (ID: DG01623) and It's Reported Resistant Information

• Name: Ripretinib
• Synonyms: 1442472-39-0; DCC-2618; N-{4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3- yl]-2-fluorophenyl}-N'-phenylurea; Ripretinib; Urea, N-[4-bromo-5-[1-ethyl-1,2-dihydro-7-(methylamino)-2-oxo-1,6- naphthyridin-3-yl]-2-fluorophenyl]-N'-phenyl-39-0; Ripretinib free base; Ripretinib (DCC-2618); UNII-9XW757O13D; 9XW757O13D; Ripretinib (USAN); Ripretinib [USAN]; 1442472-39-0 (free base); 1-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea; 1-[4-bromo-5-[1-ethyl-7-(methylamino)-2-oxo-1,6-naphthyridin-3-yl]-2-fluorophenyl]-3-phenylurea; Quinlock; Qinlock (TN); GTPL9175; CHEMBL4216467; SCHEMBL14999718; DCC2618; BCP29218; EX-A4883; s8757; AT18473; DB14840; HY-112306; CS-0044835; D11353; DCC 2618;DCC2618;KIT/PDGFR inhibitor;Ripretinib; N-(4-bromo-5-(1-ethyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-N'-phenylurea; Urea, N-(4-bromo-5-(1-ethyl-1,2-dihydro-7-(methylamino)-2-oxo-1,6-naphthyridin-3-yl)-2-fluorophenyl)-N'-phenyl-
• Indication:
  In total 4 Indication(s)
  Gastrointestinal stromal tumour [ICD-11: 2B5B]; Approved; [1]
  Glioma [ICD-11: 2A00]; Phase 2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Investigative; [1]
  Systemic mastocytosis [ICD-11: 2A21]; Investigative; [1]
• Target: Platelet-derived growth factor receptor alpha (PDGFRA); PGFRA_HUMAN; [1]
• Formula: 5
• IsoSMILES: CCN1C2=CC(=NC=C2C=C(C1=O)C3=CC(=C(C=C3Br)F)NC(=O)NC4=CC=CC=C4)NC
• InChI: InChI=1S/C24H21BrFN5O2/c1-3-31-21-12-22(27-2)28-13-14(21)9-17(23(31)32)16-10-20(19(26)11-18(16)25)30-24(33)29-15-7-5-4-6-8-15/h4-13H,3H2,1-2H3,(H,27,28)(H2,29,30,33)
• InChIKey: CEFJVGZHQAGLHS-UHFFFAOYSA-N
• PubChem CID: 71584930
• DrugBank ID: DB14840

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 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]

• Molecule Alteration: Missense mutation; p.D816V (c.2447A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

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

• Molecule Alteration: Missense mutation; p.D842V (c.2525A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Mastocytosis [ICD-11: 2A21]

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]

• Molecule Alteration: Missense mutation; p.D816Y (c.2446G>T)
• Sensitive Disease: Mast cell neoplasm [ICD-11: 2A21.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]

• Molecule Alteration: Missense mutation; p.V560G (c.1679T>G)
• Sensitive Disease: Mast cell neoplasm [ICD-11: 2A21.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

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) [1]

• Molecule Alteration: Missense mutation; p.N822K (c.2466T>G)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: THP-1 cells; Blood; Homo sapiens (Human); CVCL_0006
• In Vitro Model: Kasumi-1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0589
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HMC-1.2 cells; Blood; Homo sapiens (Human); CVCL_H205
• In Vitro Model: P815 cells; N.A.; Mus musculus (Mouse); CVCL_2154
• In Vitro Model: MV-4-11 cells; Peripheral blood; Homo sapiens (Human); CVCL_0064
• In Vitro Model: HMC-1.1 cells; Peripheral blood; Homo sapiens (Human); CVCL_H206
• In Vitro Model: EOL1 cells; Peripheral blood; Homo sapiens (Human); CVCL_0258
• In Vitro Model: CHO-K1 cells; Ovary; Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); CVCL_0214
• In Vivo Model: Female Hsd:Athymic Nude-Foxn1nu nude mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: IC50 assay

References

• Ref 1: Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA VariantsCancer Cell. 2019 May 13;35(5):738-751.e9. doi: 10.1016/j.ccell.2019.04.006.