Details of the Drug

General Information of Drug (ID: DM0E9BR)

• Drug Name: Staurosporine
• Synonyms: staurosporine; Staurosporin; (+)-Staurosporine; Antibiotic 230; 62996-74-1; Antibiotic AM 2282; CCRIS 3272; AM-2282; UNII-H88EPA0A3N; Alkaloid AM-2282 from Streptomyces; H88EPA0A3N; CHEMBL388978; CHEBI:15738; CGP 39360; 8,12-Epoxy-1H,8H-2,7b,12a-triazadibenzo(a,g)cyclonona(cde)trinden-1-one, 2,3,9,10,11,12-hexahydro-9-methoxy-8-methyl-10-(methylamino)-, (8alpha,9beta,10beta,12alpha)-(+)-

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); 466.5
  Topological Polar Surface Area (xlogp); 3.2
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C28H26N4O3
  IUPAC Name: (2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one
  Canonical SMILES: C[C@@]12[C@@H]([C@@H](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)NC)OC
  InChI: InChI=1S/C28H26N4O3/c1-28-26(34-3)17(29-2)12-20(35-28)31-18-10-6-4-8-14(18)22-23-16(13-30-27(23)33)21-15-9-5-7-11-19(15)32(28)25(21)24(22)31/h4-11,17,20,26,29H,12-13H2,1-3H3,(H,30,33)/t17-,20-,26-,28+/m1/s1
  InChIKey: HKSZLNNOFSGOKW-FYTWVXJKSA-N
• Cross-matching ID:
  PubChem CID: 44259
  ChEBI ID: CHEBI:15738
  CAS Number: 62996-74-1
  DrugBank ID: DB02010
  TTD ID: D0E3TC
  VARIDT ID: DR00790

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	TTJ3E9X	IKKB_HUMAN	Inhibitor	[2]
Protein kinase C (PRKC)	TTYVX59	NOUNIPROTAC	Inhibitor	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

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
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.39E-02	1.07E-01	2.80E-01

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] 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.
• [3] Protein kinase C zeta isoform is critical for proliferation in human glioblastoma cell lines. J Neurooncol. 2000 Apr;47(2):109-15.
• [4] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [5] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [6] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [7] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [8] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [9] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [10] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.
• [11] How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer. 2002 Sep;2(9):705-13.
• [12] 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.
• [13] The NF B pathway: a therapeutic target in glioblastoma. Oncotarget. 2011 August; 2(8): 646-653.
• [14] 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.
• [15] 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.
• [16] Company report (Millennium)
• [17] Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52.
• [18] Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2419-22.
• [19] 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.
• [20] Characterization of the interaction of hypericin with protein kinase C in U-87 MG human glioma cells. Photochem Photobiol. 2006 May-Jun;82(3):720-8.
• [21] Targeting the protein kinase C family: are we there yet. Nat Rev Cancer. 2007 Jul;7(7):554-62.
• [22] Effect of anti-tumor agents cisplatin and cycloplatam on membrane protein kinase C activity in murine T-lymphocytes. Biokhimiia. 1996 Oct;61(10):1866-73.
• [23] What's next in the pipeline. Am J Transplant. 2008 Oct;8(10):1972-81.
• [24] WO patent application no. 2014,0853,81, Pharmaceutical combinations.
• [25] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [26] The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells. Int J Oncol. 2009 Dec;35(6):1463-71.
• [27] Inhibitory effect of glutamate release from rat cerebrocortical synaptosomes by dextromethorphan and its metabolite 3-hydroxymorphinan. Neurochem Int. 2009 Jul;54(8):526-34.
• [28] Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts. J Korean Soc Transplant. 2012 Dec;26(4):248-253.
• [29] Protein kinase C as a molecular target for cancer prevention by selenocompounds. Nutr Cancer. 2001;40(1):55-63.