Drug Information

Drug (ID: DG01652) and It's Reported Resistant Information

• Name: PRN1371
• Synonyms: PRN1371; 1802929-43-6; PRN-1371; 8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one; UNII-S3OPE9IA3Q; S3OPE9IA3Q; 6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)-8-[3-(4-prop-2-enoylpiperazin-1-yl)propyl]pyrido[2,3-d]pyrimidin-7-one; GTPL9788; CHEMBL4068509; SCHEMBL16993012; US9567334, Example 6; BDBM286984; BCP20493; EX-A2927; NSC801089; s8578; CCG-270053; CS-7485; NSC-801089; compound 34 [PMID: 28665128]; BP179867; HY-101768; J3.662.238E; C92492; A936037; Q29213602
• Indication:
  In total 3 Indication(s)
  Gastrointestinal stromal tumour [ICD-11: 2B5B]; Phase 1; [1]
  Mast cell leukaemia [ICD-11: 2A21]; Phase 1; [1]
  Systemic mastocytosis [ICD-11: 2A21]; Phase 1; [1]
• Target: Platelet-derived growth factor receptor alpha (PDGFRA); PGFRA_HUMAN; [1]
• Formula: 9
• IsoSMILES: CNC1=NC=C2C=C(C(=O)N(C2=N1)CCCN3CCN(CC3)C(=O)C=C)C4=C(C(=CC(=C4Cl)OC)OC)Cl
• InChI: InChI=1S/C26H30Cl2N6O4/c1-5-20(35)33-11-9-32(10-12-33)7-6-8-34-24-16(15-30-26(29-2)31-24)13-17(25(34)36)21-22(27)18(37-3)14-19(38-4)23(21)28/h5,13-15H,1,6-12H2,2-4H3,(H,29,30,31)
• InChIKey: PUIXMSRTTHLNKI-UHFFFAOYSA-N
• PubChem CID: 118295624
• TTD Drug ID: D0UO2P

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

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

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 1 (FGFR1) [1]

• Molecule Alteration: Missense mutation; p.V561M (c.1681G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Missense mutation; p.N550K (c.1650T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Missense mutation; p.K660E (c.1978A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Missense mutation; p.K660N (c.1980G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Key Molecule: Fibroblast growth factor receptor 3 (FGFR3) [1]

• Molecule Alteration: Missense mutation; p.K650M (c.1949A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [1]

• Molecule Alteration: Missense mutation; p.N549K (c.1647T>G)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: FGF/FGFR signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: RT4 cells; Bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: RT112 cells; Bladder; Homo sapiens (Human); CVCL_1670
• In Vitro Model: AN3CA cells; Ovary; Homo sapiens (Human); CVCL_0028
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: SNU878 cells; Liver; Homo sapiens (Human); CVCL_5102
• In Vitro Model: SNU16 cells; Ascites; Homo sapiens (Human); CVCL_0076
• In Vitro Model: OPM2 cells; Peripheral blood; Homo sapiens (Human); CVCL_1625
• In Vitro Model: LI7 cells; Liver; Homo sapiens (Human); CVCL_3840
• In Vitro Model: JHH7 cells; Liver; Homo sapiens (Human); CVCL_2805
• In Vivo Model: Nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.

References

• Ref 1: The Irreversible Covalent Fibroblast Growth Factor Receptor Inhibitor PRN1371 Exhibits Sustained Inhibition of FGFR after Drug ClearanceMol Cancer Ther. 2017 Dec;16(12):2668-2676. doi: 10.1158/1535-7163.MCT-17-0309. Epub 2017 Oct 4.