Details of the Drug

General Information of Drug (ID: DM82Y75)

• Drug Name: PIRINIXIC ACID
• Synonyms: Pirinixic acid; 50892-23-4; WY-14643; [4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid; WY-14,643; WY14643; Wyeth 14,643; Wy 14643; Pirinixic acid [INN]; WY-14643 (Pirinixic Acid); (4-Chloro-6-(2,3-xylidino)-2-pyrimidinylthio)acetic acid; UNII-86C4MRT55A; C14H14ClN3O2S; CCRIS 133; Acidum pirinixicum [INN-Latin]; Acide pirinixique [INN-French]; Acido pirinixico [INN-Spanish]; NSC310038; NSC-310038; NSC 310038; BRN 0759945; ((4-Chloro-6-((2,3-dimethylphenyl)amino)-2-pyrimidinyl)thio)acetic acid; Acetic acid, ((4-chloro-6-(

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary fibrosis	CB03.4	Preclinical	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 323.8
  Logarithm of the Partition Coefficient (xlogp); 4.2
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C14H14ClN3O2S
  IUPAC Name: 2-[4-chloro-6-(2,3-dimethylanilino)pyrimidin-2-yl]sulfanylacetic acid
  Canonical SMILES: CC1=C(C(=CC=C1)NC2=CC(=NC(=N2)SCC(=O)O)Cl)C
  InChI: InChI=1S/C14H14ClN3O2S/c1-8-4-3-5-10(9(8)2)16-12-6-11(15)17-14(18-12)21-7-13(19)20/h3-6H,7H2,1-2H3,(H,19,20)(H,16,17,18)
  InChIKey: SZRPDCCEHVWOJX-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5694
  ChEBI ID: CHEBI:32509
  CAS Number: 50892-23-4
  TTD ID: D09XCX

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Gene/Protein Processing	[3]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Gene/Protein Processing	[4]
Angiopoietin-related protein 4 (ANGPTL4)	OTQL5SPX	ANGL4_HUMAN	Gene/Protein Processing	[5]
Ankyrin repeat domain-containing protein 26 (ANKRD26)	OT2ENKKV	ANR26_HUMAN	Gene/Protein Processing	[6]
Ankyrin repeat domain-containing protein 30A (ANKRD30A)	OTJXYAE5	AN30A_HUMAN	Gene/Protein Processing	[6]
Apolipoprotein A-I (APOA1)	OT5THARI	APOA1_HUMAN	Gene/Protein Processing	[7]
Aryl hydrocarbon receptor (AHR)	OTFE4EYE	AHR_HUMAN	Gene/Protein Processing	[8]
Bcl-2-modifying factor (BMF)	OT90NSLI	BMF_HUMAN	Gene/Protein Processing	[5]
Bifunctional epoxide hydrolase 2 (EPHX2)	OTPTRCNW	HYES_HUMAN	Gene/Protein Processing	[9]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Gene/Protein Processing	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Pulmonary fibrosis
• ICD Disease Classification: CB03.4

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Peroxisome proliferator-activated receptor alpha (PPARA)	DTT	PPARA	1.74E-01	-0.17	-0.3

References

• [1] Targeting metabolic dysregulation for fibrosis therapy. Nat Rev Drug Discov. 2020 Jan;19(1):57-75.
• [2] O-arylmandelic acids as highly selective human PPAR alpha/gamma agonists. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3185-90.
• [3] WY 14,643 inhibits human aldose reductase activity. J Enzyme Inhib Med Chem. 2006 Oct;21(5):569-73.
• [4] Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
• [5] PPAR-mediated responses in human adult liver stem cells: In vivo/in vitro and cross-species comparisons. J Steroid Biochem Mol Biol. 2013 Nov;138:236-47. doi: 10.1016/j.jsbmb.2013.06.004. Epub 2013 Jun 27.
• [6] Immunoselection and characterization of a human genomic PPAR binding fragment located within POTE genes. Biochimie. 2007 Mar;89(3):329-36. doi: 10.1016/j.biochi.2006.09.017. Epub 2006 Oct 18.
• [7] Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem. 1994 Dec 9;269(49):31012-8.
• [8] PPARalpha activation potentiates AhR-induced CYP1A1 expression. Toxicology. 2005 Dec 15;216(2-3):122-8.
• [9] Expression of cytochrome P450 epoxygenases and soluble epoxide hydrolase is regulated by hypolipidemic drugs in dose-dependent manner. Toxicol Appl Pharmacol. 2018 Sep 15;355:156-163.
• [10] Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.