Details of the Drug

General Information of Drug (ID: DM157OQ)

• Drug Name: 5-Bromo-6-methoxy-9H-beta-carboline
• Synonyms: 5-bromo-6-methoxy-beta-carboline; CHEMBL310975; 5-Bromo-6-methoxy-9H-beta-carboline; SCHEMBL6465779; BDBM50130233

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 277.12
  Topological Polar Surface Area (xlogp); 3
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C12H9BrN2O
  IUPAC Name: 5-bromo-6-methoxy-9H-pyrido[3,4-b]indole
  Canonical SMILES: COC1=C(C2=C(C=C1)NC3=C2C=CN=C3)Br
  InChI: InChI=1S/C12H9BrN2O/c1-16-10-3-2-8-11(12(10)13)7-4-5-14-6-9(7)15-8/h2-6,15H,1H3
  InChIKey: NXKWYFQQPHBFII-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 11414735
  TTD ID: D01OBJ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
IKKA messenger RNA (IKKA mRNA)	TT1F8OQ	IKKA_HUMAN	Inhibitor	[1]
Inhibitor of nuclear factor kappa-B kinase (IKK)	TTRPDBG	NOUNIPROTAC	Inhibitor	[1]
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	TTJ3E9X	IKKB_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	DTT	IKBKB	5.74E-08	0.26	0.88

References

• [1] Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2419-22.
• [2] Novel NF-B inhibitors: a patent review (2011 - 2014).Expert Opin Ther Pat. 2015 Mar;25(3):319-34.
• [3] Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKepsilon kinases. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7169-73.
• [4] Inhibition of NF-kappa B activation by arsenite through reaction with a critical cysteine in the activation loop of Ikappa B kinase. J Biol Chem. 2000 Nov 17;275(46):36062-6.
• [5] Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104.
• [6] Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
• [7] IkappaB kinase, a molecular target for inhibition by 4-hydroxy-2-nonenal. J Biol Chem. 2001 May 25;276(21):18223-8.
• [8] A highly selective inhibitor of I kappa B kinase, BMS-345541, blocks both joint inflammation and destruction in collagen-induced arthritis in mice. Arthritis Rheum. 2003 Sep;48(9):2652-9.
• [9] How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer. 2002 Sep;2(9):705-13.
• [10] The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66.
• [11] The NF B pathway: a therapeutic target in glioblastoma. Oncotarget. 2011 August; 2(8): 646-653.
• [12] Inhibition of I B phosphorylation prevents load-induced cardiac dysfunction in mice. Am J Physiol Heart Circ Physiol. 2012 Dec 15;303(12):H1435-45.
• [13] I B kinase beta inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. Clin Exp Allergy. 2011 Jan;41(1):104-15.
• [14] Company report (Millennium)
• [15] Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52.
• [16] UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst. 1996 Jul 17;88(14):956-65.
• [17] Evolution of the thienopyridine class of inhibitors of IkappaB kinase-beta: part I: hit-to-lead strategies. J Med Chem. 2006 May 18;49(10):2898-908.
• [18] Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem. 2006 Jun 15;49(12):3563-80.
• [19] US patent application no. 6,395,545, Antisense modulation of inhibitor-kappa B kinase-alpha expression.