Drug Information

Drug (ID: DG01601) and It's Reported Resistant Information

• Name: Pilaralisib
• Synonyms: Pilaralisib; 934526-89-3; XL-147; SAR245408; SAR-245408; UNII-60ES45KTMK; Pilaralisib (XL147); 60ES45KTMK; 2-amino-N-[3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl]-2-methylpropanamide; 2-amino-N-(3-(N-(3-((2-chloro-5-methoxyphenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide.; SAR 245408; Pilaralisib [USAN:INN]; Pilaralisib, SAR245408; SCHEMBL189422; CHEMBL3360203; SCHEMBL14921345; SCHEMBL16154579; EX-A196; AMY10846; BCP15312; BDBM50197062; MFCD26142605; NSC791227; NSC800853; s7645; AKOS026750450; ZINC100472223; CCG-264704; CS-1546; DB11772; NSC-791227; NSC-800853; SB16574; Pilaralisib(XL-147; SAR245408); NCGC00378973-02; 2-Amino-n-(3-(N-(3-((2-chloro-5-methoxyphenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide; 2-amino-N-[3-({3-[(2-chloro-5-methoxyphenyl)amino]quinoxalin-2-yl}sulfamoyl)phenyl]-2-methylpropanamide; AC-33122; AS-56300; DA-40388; HY-16526; FT-0744481; A859771
• Target: .; NOUNIPROTAC; [1]
• Formula: 8
• IsoSMILES: CC(C)(C(=O)NC1=CC(=CC=C1)S(=O)(=O)NC2=NC3=CC=CC=C3N=C2NC4=C(C=CC(=C4)OC)Cl)N
• InChI: InChI=1S/C25H25ClN6O4S/c1-25(2,27)24(33)28-15-7-6-8-17(13-15)37(34,35)32-23-22(29-19-9-4-5-10-20(19)30-23)31-21-14-16(36-3)11-12-18(21)26/h4-14H,27H2,1-3H3,(H,28,33)(H,29,31)(H,30,32)
• InChIKey: QINPEPAQOBZPOF-UHFFFAOYSA-N
• PubChem CID: 56599306
• DrugBank ID: DB11772

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

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.E545K (c.1633G>A)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: U87-MG cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: LS174T cells; Colon; Homo sapiens (Human); CVCL_1384
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: Ramos cells; Ascites; Homo sapiens (Human); CVCL_0597
• In Vitro Model: OVCAR-3 cells; Ascites; Homo sapiens (Human); CVCL_0465
• In Vivo Model: Athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: ViaLight HS assay; Apo-ONE Homogeneous Caspase-3/7 assay; Soft agar assay

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [1]

• Molecule Alteration: Missense mutation; p.T798M (c.2393_2394delCAinsTG)
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: MCF10A cells; Breast; Homo sapiens (Human); CVCL_0598
• In Vivo Model: Athymic female mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: HER2T798M sequencing assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of Pilaralisib by aberration of the drug's therapeutic target

References

• Ref 1: Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2Clin Cancer Res. 2013 Oct 1;19(19):5390-401. doi: 10.1158/1078-0432.CCR-13-1038. Epub 2013 Aug 15.
• Ref 2: The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor ModelsMol Cancer Ther. 2015 Apr;14(4):931-40. doi: 10.1158/1535-7163.MCT-14-0833. Epub 2015 Jan 30.