Details of the Drug

General Information of Drug (ID: DMG8KS9)

• Drug Name: Phenanthrene-9,10-dione
• Synonyms: Phenanthrene-9,10-dione; 9,10-Phenanthrenequinone; 84-11-7; Phenanthrenequinone; 9,10-PHENANTHRENEDIONE; 9,10-Phenanthraquinone; Phenanthraquinone; 9,10-Phenanthroquinone; 9-10 Phenanthrene quinone; UNII-42L7BZ8H74; CCRIS 7615; Phenanthrene, 9,10-dihydro-9,10-dioxo-; HSDB 4489; EINECS 201-515-5; NSC 10446; phenanthrene-9,10-quinone; BRN 0608838; SMR000150826; CHEMBL51931; MLS000881132; MLS000571180; AI3-23739; CHEBI:37454; YYVYAPXYZVYDHN-UHFFFAOYSA-N; 42L7BZ8H74; MFCD00001163; 9,10-dihydrophenanthrene-9,10-dione; AK-96664

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); 208.21
  Logarithm of the Partition Coefficient (xlogp); 2.5
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C14H8O2
  IUPAC Name: phenanthrene-9,10-dione
  Canonical SMILES: C1=CC=C2C(=C1)C3=CC=CC=C3C(=O)C2=O
  InChI: InChI=1S/C14H8O2/c15-13-11-7-3-1-5-9(11)10-6-2-4-8-12(10)14(13)16/h1-8H
  InChIKey: YYVYAPXYZVYDHN-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 6763
  ChEBI ID: CHEBI:37454
  CAS Number: 84-11-7
  TTD ID: D0Q2YJ
  INTEDE ID: DR0026

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cholinesterase (BCHE)	TTEB0GD	CHLE_HUMAN	Inhibitor	[1]
Liver carboxylesterase (CES1)	TTMF541	EST1_HUMAN	Inhibitor	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
NADPH-dependent carbonyl reductase 1 (CBR1)	DE9JFMC	CBR1_HUMAN	Substrate	[2]
Small intestine reductase (AKR1B10)	DEP6GT1	AK1BA_HUMAN	Substrate	[3]
NADPH-dependent carbonyl reductase 3 (CBR3)	DEIVKZ8	CBR3_HUMAN	Substrate	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Gene/Protein Processing	[3]
Aflatoxin B1 aldehyde reductase member 2 (AKR7A2)	OTGEDDM2	ARK72_HUMAN	Biotransformations	[4]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Biotransformations	[4]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Gene/Protein Processing	[3]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Regulation of Drug Effects	[5]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Regulation of Drug Effects	[5]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Gene/Protein Processing	[6]
Aldo-keto reductase family 1 member C4 (AKR1C4)	OTW2MMOF	AK1C4_HUMAN	Biotransformations	[7]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Gene/Protein Processing	[6]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[6]

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
Liver carboxylesterase (CES1)	DTT	CES1	3.82E-08	1.86	1.9
Small intestine reductase (AKR1B10)	DME	AKR1B10	3.34E-03	-1.14E-01	-6.72E-01
NADPH-dependent carbonyl reductase 3 (CBR3)	DME	CBR3	2.30E-04	-5.58E-01	-1.63E+00
NADPH-dependent carbonyl reductase 1 (CBR1)	DME	CBR1	2.53E-10	1.09E+00	2.10E+00

References

• [1] Planarity and constraint of the carbonyl groups in 1,2-diones are determinants for selective inhibition of human carboxylesterase 1. J Med Chem. 2007 Nov 15;50(23):5727-34.
• [2] Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
• [3] Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10. Toxicol Appl Pharmacol. 2014 Jul 15;278(2):180-9.
• [4] Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. Biochem J. 1999 Oct 15;343 Pt 2(Pt 2):487-504.
• [5] An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies. Biochem Pharmacol. 2008 Jan 15;75(2):484-93.
• [6] Facilitation of 9,10-phenanthrenequinone-elicited neuroblastoma cell apoptosis by NAD(P)H:quinone oxidoreductase 1. Chem Biol Interact. 2018 Jan 5;279:10-20.
• [7] Retinaldehyde is a substrate for human aldo-keto reductases of the 1C subfamily. Biochem J. 2011 Dec 15;440(3):335-44.