Drug Information

Drug (ID: DG01585) and It's Reported Resistant Information

• Name: CH-5132799
• Synonyms: CH5132799; 1007207-67-1; CH-5132799; 5-(7-(methylsulfonyl)-2-morpholino-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrimidin-2-amine; CH 5132799; UNII-JCL936W835; CHEMBL1684984; CH5132799 (PA-799); JCL936W835; 5-(7-methylsulfonyl-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl)pyrimidin-2-amine; 5-(7-Methanesulfonyl-2-Morpholin-4-Yl-6,7-Dihydro-5h-Pyrrolo[2,3-D]pyrimidin-4-Yl)-Pyrimidin-2-Ylamine; C15H19N7O3S; (5-(7-Methylsulfonyl-2-(morpholin-4-yl)-6,7-dihydro-5H-pyrrolo(2,3-d)pyrimidin-4-yl)pyrimidin-2-yl)amine; izorlisib; [5-[7-Methylsulfonyl-2-(morpholin-4-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-yl]amine; MLS006010989; GTPL7743; QCR-47; SCHEMBL2377154; DTXSID40678540; EX-A997; MEN1611; SYN1146; HMS3656H15; HMS3750I19; PA799; AOB87718; BCP02894; MEN-1611; 2316AH; BDBM50338197; MFCD22419020; NSC762382; NSC800984; PA-799; s2699; ZINC66074200; AKOS025404886; BCP9000513; CCG-264982; CS-0981; DB13051; NSC-762382; NSC-800984; SB20410; NCGC00346650-01; NCGC00346650-06; 5-[7-(Methanesulfonyl)-2-(morpholin-4-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine; AC-28422; AS-16285; HY-15466; SMR004702790; BCP0726000261; SW220190-1; J-000203; Q27075949; 2-Pyrimidinamine, 5-[6,7-dihydro-7-(methylsulfonyl)-2-(4-morpholinyl)-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-; 5-[7-(methylsulfonyl)-2-(morpholin-4-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine; 5-[7-methanesulfonyl-2-(morpholin-4-yl)-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-4-yl]pyrimidin-2-amine
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1/2; [1]
• Target: Fibroblast growth factor receptor 2 (FGFR2); FGFR2_HUMAN; [2]
• Formula: 3
• IsoSMILES: CS(=O)(=O)N1CCC2=C(N=C(N=C21)N3CCOCC3)C4=CN=C(N=C4)N
• InChI: InChI=1S/C15H19N7O3S/c1-26(23,24)22-3-2-11-12(10-8-17-14(16)18-9-10)19-15(20-13(11)22)21-4-6-25-7-5-21/h8-9H,2-7H2,1H3,(H2,16,17,18)
• InChIKey: JEGHXKRHKHPBJD-UHFFFAOYSA-N
• PubChem CID: 49784945
• TTD Drug ID: D0D4VV
• DrugBank ID: DB13051

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

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.E542K (c.1624G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vitro Model: IGROV1 cells; Ovary; Homo sapiens (Human); CVCL_1304
• In Vitro Model: GXF97 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.E542K (c.1624G>A) in gene PIK3CA cause the sensitivity of CH-5132799 by aberration of the drug's therapeutic target

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vitro Model: IGROV1 cells; Ovary; Homo sapiens (Human); CVCL_1304
• In Vitro Model: GXF97 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.H1047R (c.3140A>G) in gene PIK3CA cause the sensitivity of CH-5132799 by aberration of the drug's therapeutic target

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vitro Model: IGROV1 cells; Ovary; Homo sapiens (Human); CVCL_1304
• In Vitro Model: GXF97 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of CH-5132799 by aberration of the drug's therapeutic target

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: ARRAY system assay
• Experiment for Drug Resistance: Presto blue assay

Endometrial cancer [ICD-11: 2C76]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.H1047Y (c.3139C>T)
• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vitro Model: IGROV1 cells; Ovary; Homo sapiens (Human); CVCL_1304
• In Vitro Model: GXF97 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.H1047Y (c.3139C>T) in gene PIK3CA cause the sensitivity of CH-5132799 by aberration of the drug's therapeutic target

Prostate cancer [ICD-11: 2C82]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.Q546R (c.1637A>G)
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KPL-4 cells; Breast; Homo sapiens (Human); CVCL_5310
• In Vitro Model: IGROV1 cells; Ovary; Homo sapiens (Human); CVCL_1304
• In Vitro Model: GXF97 cells; N.A.; .; N.A.
• In Vivo Model: Female BALB-nu/nu mouse xenograft model; Mus musculus
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: The missense mutation p.Q546R (c.1637A>G) in gene PIK3CA cause the sensitivity of CH-5132799 by aberration of the drug's therapeutic target

References

• Ref 1: First-in-human study of CH5132799, an oral class I PI3K inhibitor, studying toxicity, pharmacokinetics, and pharmacodynamics, in patients with metastatic cancerClin Cancer Res. 2014 Dec 1;20(23):5908-17. doi: 10.1158/1078-0432.CCR-14-1315. Epub 2014 Sep 17.
• Ref 2: The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutationsClin Cancer Res. 2011 May 15;17(10):3272-81. doi: 10.1158/1078-0432.CCR-10-2882. Epub 2011 May 10.