Drug Information

Drug (ID: DG00289) and It's Reported Resistant Information

• Name: I-BET151
• Synonyms: GSK1210151A
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Brain cancer [ICD-11: 2A00]; [1]
• Target: Bromodomain-containing protein 2 (BRD2); BRD2_HUMAN; [1]
• Target: Bromodomain-containing protein 3 (BRD3); BRD3_HUMAN; [1]
• Target: Bromodomain-containing protein 4 (BRD4); BRD4_HUMAN; [1]
• Formula: C23H21N5O3
• IsoSMILES: CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)[C@H](C)C5=CC=CC=N5)OC
• InChI: 1S/C23H21N5O3/c1-12-21(14(3)31-27-12)16-9-18-15(10-20(16)30-4)22-19(11-25-18)26-23(29)28(22)13(2)17-7-5-6-8-24-17/h5-11,13H,1-4H3,(H,26,29)/t13-/m1/s1
• InChIKey: VUVUVNZRUGEAHB-CYBMUJFWSA-N
• PubChem CID: 52912189
• ChEBI ID: CHEBI:95083
• TTD Drug ID: D0WU1S

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [1]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Brain cancer [ICD-11: 2A00]
• The Specified Disease: Glioblastoma multiforme
• The Studied Tissue: Brain
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.30E-10; Fold-change: 5.40E+00; Z-score: 6.58E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: U87Luc cells; Brain; Homo sapiens (Human); CVCL_5J12
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Colony forming assay; Flow cytometry assay
• Mechanism Description: The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation to promote I-bet151 resistance in Glioblastoma.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Bromodomain-containing protein 4 (BRD4) [1]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Brain cancer [ICD-11: 2A00]
• The Specified Disease: Neuroectodermal tumor
• The Studied Tissue: Brainstem tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.90E-08; Fold-change: 1.04E-01; Z-score: 9.87E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: U87Luc cells; Brain; Homo sapiens (Human); CVCL_5J12
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Colony forming assay; Flow cytometry assay
• Mechanism Description: The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation to promote I-bet151 resistance in Glioblastoma.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Hepatocyte growth factor receptor (MET) [2]

• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: HGF-Met signaling pathway; Regulation; N.A.
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Calu-1 cells; Lung; Homo sapiens (Human); CVCL_0608
• In Vitro Model: H157 cells; Lung; Homo sapiens (Human); CVCL_2458
• In Vitro Model: NCI- H460 cells; Pleural effusion; Homo sapiens (Human); CVCL_0459
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Sulforhodamine B assay
• Mechanism Description: JQ1, I-BET151, or BRD4 silencing all downregulated Met and inhibited both NSCLC cell viability in vitro and tumor growth in vivo.

References

• Ref 1: The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation. Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8326-31. doi: 10.1073/pnas.1424220112. Epub 2015 Jun 25.
• Ref 2: Targeting BET proteins inhibited the growth of non-small cell lung carcinoma through downregulation of Met expression. Cell Biol Int. 2023 Mar;47(3):622-633.