Details of the Drug

General Information of Drug (ID: DMCP1G9)

• Drug Name: chelerythrine
• Synonyms: broussonpapyrine; cheleritrine; chelerythrine hydroxide; toddalin

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); 348.4
  Logarithm of the Partition Coefficient (xlogp); 4.6
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C21H18NO4+
  IUPAC Name: 1,2-dimethoxy-12-methyl-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
  Canonical SMILES: C[N+]1=C2C(=C3C=CC(=C(C3=C1)OC)OC)C=CC4=CC5=C(C=C42)OCO5
  InChI: InChI=1S/C21H18NO4/c1-22-10-16-13(6-7-17(23-2)21(16)24-3)14-5-4-12-8-18-19(26-11-25-18)9-15(12)20(14)22/h4-10H,11H2,1-3H3/q+1
  InChIKey: LLEJIEBFSOEYIV-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 2703
  ChEBI ID: CHEBI:78373
  CAS Number: 34316-15-9
  TTD ID: D0T9ZL
  VARIDT ID: DR00988

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fungal Protein kinase A (Fung ypkA)	TTYVI76	Q56921_YEREN	Inhibitor	[2]
P2X purinoceptor 7 (P2RX7)	TT473XN	P2RX7_HUMAN	Modulator (allosteric modulator)	[1]
PKC-epsilon messenger RNA (PRKCE mRNA)	TT57MT2	KPCE_HUMAN	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[4]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Protein Interaction/Cellular Processes	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Protein Interaction/Cellular Processes	[5]
Caspase-6 (CASP6)	OTXLD3EC	CASP6_HUMAN	Protein Interaction/Cellular Processes	[5]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Protein Interaction/Cellular Processes	[5]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Protein Interaction/Cellular Processes	[5]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Gene/Protein Processing	[6]
Neurotensin/neuromedin N (NTS)	OTPGDNQS	NEUT_HUMAN	Gene/Protein Processing	[7]
Prelamin-A/C (LMNA)	OT3SG7ZR	LMNA_HUMAN	Protein Interaction/Cellular Processes	[5]
Prostaglandin E synthase 3 (PTGES3)	OTPPQWI0	TEBP_HUMAN	Protein Interaction/Cellular Processes	[5]

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
P2X purinoceptor 7 (P2RX7)	DTT	P2RX7	1.11E-06	0.37	0.49
Multidrug resistance-associated protein 2 (ABCC2)	DTP	MRP2	7.16E-01	-1.28E-02	-6.06E-02

References

• [1] Chelerythrine and other benzophenanthridine alkaloids block the human P2X7 receptor. Br J Pharmacol. 2004 Jul;142(6):1015-9.
• [2] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [3] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [4] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [5] An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death. J Biol Chem. 2015 Aug 21;290(34):20841-20855. doi: 10.1074/jbc.M115.644179. Epub 2015 Jun 29.
• [6] Activation of VPAC1 receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion. Br J Pharmacol. 2004 Feb;141(4):698-708. doi: 10.1038/sj.bjp.0705597. Epub 2004 Jan 26.
• [7] Protein kinase C inhibitors alter neurotensin receptor binding and function in prostate cancer PC3 cells. Regul Pept. 2008 Apr 10;147(1-3):96-109. doi: 10.1016/j.regpep.2008.01.009. Epub 2008 Feb 11.