Drug Information

Drug (ID: DG01596) and It's Reported Resistant Information

• Name: APR-246
• Synonyms: APR-246; 5291-32-7; PRIMA-1MET; Eprenetapopt; APR 246; 2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one; 2-(Hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one; Prima 1MET; Eprenetapopt [USAN]; MLS006010767; APR246; SCHEMBL2228161; 3-Quinuclidinone, 2-(hydroxymethyl)-2-(methoxymethyl)-; CHEMBL3186011; SCHEMBL21636035; PRIMA-1MET(APR-246); APR-246 (PRIMA-1MET); BCP20294; EX-A2772; MFCD20620963; NSC791496; s7724; WHO 11387; 1-Azabicyclo(2.2.2)octan-3-one, 2-(hydroxymethyl)-2-(methoxymethyl)-; AKOS024457764; CCG-266578; CS-7614; DB11684; NSC-791496; SB19737; NCGC00346881-01; AC-32964; AS-72033; BA176962; HY-19980; SMR004701457; A901731; Q27294965; 2-hydroxymethyl-2-methoxymethyl-1-azabicyclo[2.2.2]octan-3-one
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Phase 2; [1]
• Target: Bromodomain-containing protein 2 (BRD2); BRD2_HUMAN; [2]
• Target: Bromodomain-containing protein 3 (BRD3); BRD3_HUMAN; [2]
• Target: Bromodomain-containing protein 4 (BRD4); BRD4_HUMAN; [2]
• Formula: 3
• IsoSMILES: COCC1(C(=O)C2CCN1CC2)CO
• InChI: InChI=1S/C10H17NO3/c1-14-7-10(6-12)9(13)8-2-4-11(10)5-3-8/h8,12H,2-7H2,1H3
• InChIKey: BGBNULCRKBVAKL-UHFFFAOYSA-N
• PubChem CID: 52918385
• TTD Drug ID: D0WU1S
• DrugBank ID: DB11684

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

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [2]

• Molecule Alteration: Missense mutation; p.V173M (c.517G>A)
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Blood; N.A.
• Experiment for Molecule Alteration: TP53 gene mutation status analysis
• Experiment for Drug Resistance: Pharmacokinetic Analysis
• Mechanism Description: The missense mutation p.V173M (c.517G>A) in gene TP53 cause the sensitivity of APR-246 by unusual activation of pro-survival pathway

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

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

• Molecule Alteration: Missense mutation; p.S241F (c.722C>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: DMS456 cells; Lung; Homo sapiens (Human); CVCL_0B92
• In Vivo Model: Nude male NMRI mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.S241F (c.722C>T) in gene TP53 cause the sensitivity of APR-246 by aberration of the drug's therapeutic target

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

• Molecule Alteration: Missense mutation; p.R273L (c.818G>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: DMS456 cells; Lung; Homo sapiens (Human); CVCL_0B92
• In Vivo Model: Nude male NMRI mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.R273L (c.818G>T) in gene TP53 cause the sensitivity of APR-246 by aberration of the drug's therapeutic target

References

• Ref 1: PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53Clin Cancer Res. 2011 May 1;17(9):2830-41. doi: 10.1158/1078-0432.CCR-10-3168. Epub 2011 Mar 17.
• Ref 2: Targeting p53 in vivo: a first-in-human study with p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancerJ Clin Oncol. 2012 Oct 10;30(29):3633-9. doi: 10.1200/JCO.2011.40.7783. Epub 2012 Sep 10.