Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM9ZBO0)

• Drug Name: CI-972 Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 135418360
  CAS Number: CAS 115787-68-3
  TTD Drug ID: DM9ZBO0

Molecule-Related Drug Atlas

Drug(s) Targeting Purine nucleoside phosphorylase (PNP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BCX-3408	DMRSG31	Autoimmune diabetes	5A10	Phase 2	[4]
2'3'-Dideoxyinosine	DMZWNQF	N. A.	N. A.	Phase 2	[5]
Forodesine	DME2W4T	B-cell acute lymphoblastic leukaemia	2B33.3	Phase 1/2	[6]
Guanosine	DM4T5LH	N. A.	N. A.	Phase 1	[5]
Peldesine	DMHV58T	N. A.	N. A.	Phase 1	[5]
7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30)	DMSU06X	Discovery agent	N.A.	Investigative	[7]
Hypoxanthine	DMLSABI	Discovery agent	N.A.	Investigative	[5]
8-Iodo-Guanine	DM3K1EO	Discovery agent	N.A.	Investigative	[5]
8-Azaguanine	DM7VP90	Discovery agent	N.A.	Investigative	[5]
MT-Immucillin-H	DMK2FOX	Discovery agent	N.A.	Investigative	[8]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[9]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[10]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[11]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[12]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[13]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[14]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[15]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[16]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Purine nucleoside phosphorylase (PNP)	TTMCF1Y	PNPH_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Purine nucleoside phosphorylase (PNP)	OTO5NIJ2	PNPH_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002367)
• [2] Inhibitors of human purine nucleoside phosphorylase. Synthesis of pyrrolo[3,2-d]pyrimidines, a new class of purine nucleoside phosphorylase inhibitors as potentially T-cell selective immunosuppressive agents. Description of 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d] pyrimidin-4-one. J Med Chem. 1992 May 1;35(9):1605-9.
• [3] PD 141955 and CI-972: 9-deazaguanine analog purine nucleoside phosphorylase inhibitors. I. Suppression of the human mixed lymphocyte reaction (MLR). Agents Actions. 1993;39 Spec No:C96-8.
• [4] BCX-4208 (RO5092888), a Purine Nucleoside Phosphorylase (PNP) Inhibitor, Is a Novel, Potent Orally Active Anti-T-Cell and B-Cell Agent. 50th ASH Annual Meeting and Exposition. 2008.
• [5] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [6] Forodesine has high antitumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis by induction of p73 an... Blood. 2009 Aug 20;114(8):1563-75.
• [7] Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors. J Biol Chem. 1986 Sep 5;261(25):11667-73.
• [8] Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J Biol Chem. 2004 Apr 30;279(18):18103-6.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [13] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [14] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [15] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [16] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.