Drug Information

Drug (ID: DG01573) and It's Reported Resistant Information

• Name: DS-7423
• Synonyms: DS-7423; 5-{8-[(3R)-4-Acetyl-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine; SCHEMBL336466; HY-124036; CS-0084006
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Ovarian cancer [ICD-11: 2C73]; [1]
• Target: Serine/threonine-protein kinase mTOR (mTOR); MTOR_HUMAN; [1]
• Formula: 4
• IsoSMILES: C[C@@H]1CN(CCN1C(=O)C)C2=NC3=C(N2CC(F)(F)F)N=C(N=C3N4CCOCC4)C5=CN=C(N=C5)N
• InChI: InChI=1S/C22H27F3N10O2/c1-13-11-33(3-4-34(13)14(2)36)21-29-16-18(32-5-7-37-8-6-32)30-17(15-9-27-20(26)28-10-15)31-19(16)35(21)12-22(23,24)25/h9-10,13H,3-8,11-12H2,1-2H3,(H2,26,27,28)/t13-/m1/s1
• InChIKey: SOJJMSYMCLIQCZ-CYBMUJFWSA-N
• PubChem CID: 45378170

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Ovarian cancer [ICD-11: 2C73]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: TOV-21 cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: SKOV5 cells; Ovary; Homo sapiens (Human); N.A.
• In Vitro Model: RMG-I cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: OVTOKO cells; Spleen; Homo sapiens (Human); CVCL_3117
• In Vitro Model: OVSAHO cells; Abdomen; Homo sapiens (Human); CVCL_3114
• In Vitro Model: OVMANA cells; Ovary; Homo sapiens (Human); CVCL_3111
• In Vitro Model: OVKATE cells; Ovary; Homo sapiens (Human); CVCL_3110
• In Vitro Model: OVISE cells; Pelvi; Homo sapiens (Human); CVCL_3116
• In Vitro Model: OV1063 cells; Ascites; Homo sapiens (Human); CVCL_4366
• In Vitro Model: SKOV5 cells; Ovary; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blotting analysis; Luciferase assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Molecule Alteration: Missense mutation; p.S241F (c.722C>T)
• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: TOV-21 cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: SKOV6 cells; Uterus; Homo sapiens (Human); CVCL_A457
• In Vitro Model: RMG-I cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: OVTOKO cells; Spleen; Homo sapiens (Human); CVCL_3117
• In Vitro Model: OVSAHO cells; Abdomen; Homo sapiens (Human); CVCL_3114
• In Vitro Model: OVMANA cells; Ovary; Homo sapiens (Human); CVCL_3111
• In Vitro Model: OVKATE cells; Ovary; Homo sapiens (Human); CVCL_3110
• In Vitro Model: OVISE cells; Pelvi; Homo sapiens (Human); CVCL_3116
• In Vitro Model: OV1063 cells; Ascites; Homo sapiens (Human); CVCL_4366
• In Vitro Model: SKOV6 cells; Uterus; Homo sapiens (Human); CVCL_A457
• Experiment for Molecule Alteration: Western blotting analysis; Luciferase assay
• Experiment for Drug Resistance: CCK-8 assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.C420R (c.1258T>C)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: TOV-21 cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: RMG-I cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: OVTOKO cells; Spleen; Homo sapiens (Human); CVCL_3117
• In Vitro Model: OVSAHO cells; Abdomen; Homo sapiens (Human); CVCL_3114
• In Vitro Model: OVMANA cells; Ovary; Homo sapiens (Human); CVCL_3111
• In Vitro Model: OVKATE cells; Ovary; Homo sapiens (Human); CVCL_3110
• In Vitro Model: OVISE cells; Pelvi; Homo sapiens (Human); CVCL_3116
• In Vitro Model: OV1063 cells; Ascites; Homo sapiens (Human); CVCL_4366
• Experiment for Molecule Alteration: Western blotting analysis; Luciferase assay
• Experiment for Drug Resistance: CCK-8 assay

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

• Molecule Alteration: Missense mutation; p.E545V (c.1634A>T)
• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: TOV-21 cells; Ovary; Homo sapiens (Human); CVCL_3613
• In Vitro Model: SKOV4 cells; Uterus; Homo sapiens (Human); CVCL_X008
• In Vitro Model: RMG-I cells; Ascites; Homo sapiens (Human); CVCL_1662
• In Vitro Model: OVTOKO cells; Spleen; Homo sapiens (Human); CVCL_3117
• In Vitro Model: OVSAHO cells; Abdomen; Homo sapiens (Human); CVCL_3114
• In Vitro Model: OVMANA cells; Ovary; Homo sapiens (Human); CVCL_3111
• In Vitro Model: OVKATE cells; Ovary; Homo sapiens (Human); CVCL_3110
• In Vitro Model: OVISE cells; Pelvi; Homo sapiens (Human); CVCL_3116
• In Vitro Model: OV1063 cells; Ascites; Homo sapiens (Human); CVCL_4366
• In Vitro Model: SKOV4 cells; Uterus; Homo sapiens (Human); CVCL_X008
• Experiment for Molecule Alteration: Western blotting analysis; Luciferase assay
• Experiment for Drug Resistance: CCK-8 assay

References

• Ref 1: Antitumor activity and induction of TP53-dependent apoptosis toward ovarian clear cell adenocarcinoma by the dual PI3K/mTOR inhibitor DS-7423PLoS One. 2014 Feb 4;9(2):e87220. doi: 10.1371/journal.pone.0087220. eCollection 2014.