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

General Information of Drug (ID: DMBSQH9)

• Drug Name: PBF-999 Drug Info
• Synonyms: CHEMBL3942498; SCHEMBL15905362; BDBM247392; SB18883; US9447095, 42; 5-bromo-4-N-prop-2-ynyl-2-(1,2,4-triazol-1-yl)pyrimidine-4,6-diamine; 1620909-95-6

Indication

Disease Entry	ICD 11	Status	REF
Huntington disease	8A01.10	Phase 1	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Cross-matching ID:
  PubChem CID: 77107498
  TTD Drug ID: DMBSQH9

Molecule-Related Drug Atlas

Drug(s) Targeting Adenosine A2a receptor (ADORA2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Caffeine	DMKBJWP	Allergic rhinitis	CA08.0	Approved	[4]
Istradefylline	DM20VSK	Parkinson disease	8A00.0	Approved	[5]
Regadenoson	DM76VHG	Radionuclide imaging	N.A.	Approved	[6]
Tozadenant	DMATC14	Parkinson disease	8A00.0	Phase 3	[7]
Binodenoson	DMVHF8G	Hypertension	BA00-BA04	Phase 3	[8]
Apadenoson	DMD8QTC	Coronary artery disease	BA80	Phase 3	[9]
Tonapofylline	DMBH316	Acute and chronic heart failure	BD1Z	Phase 2	[10]
Dexefaroxan	DMTY4KN	Parkinson disease	8A00.0	Phase 2	[11]
AMP-579	DMJ4GPR	Hyperlipidaemia	5C80	Phase 2	[12]
BIIB014	DMH7RJ1	Parkinson disease	8A00.0	Phase 2	[13]

Drug(s) Targeting Phosphodiesterase 10A (PDE10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[14]
TAK-063	DMP1873	Schizophrenia	6A20	Phase 2	[15]
PF-02545920	DMJPE61	Huntington disease	8A01.10	Phase 2	[16]
OMS824	DMA4OGL	Huntington disease	8A01.10	Phase 2	[17]
Lu AF11167	DMJOYNZ	Schizophrenia	6A20	Phase 2	[18]
FRM-6308	DMNCOE1	Schizophrenia	6A20	Phase 1b	[19]
RG7203	DMYX4NP	Schizophrenia	6A20	Phase 1	[20]
AMG 579	DMRMC7U	Schizophrenia	6A20	Phase 1	[21]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[22]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2	DM4CSBD	N. A.	N. A.	Patented	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adenosine A2a receptor (ADORA2A)	TTM2AOE	AA2AR_HUMAN	Antagonist	[3]
Phosphodiesterase 10A (PDE10)	TTJW4LU	PDE10_HUMAN	Inhibitor	[3]

References

• [1] ClinicalTrials.gov (NCT02208934) Study To Assess the Safety and Tolerability of Single Ascending Oral Doses of PBF-999 in Healthy Young Male Volunteers. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT03786484) Study of PBF-999 in Solid Tumour Advanced Cancer. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of Palobiofarma.
• [4] Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol. 2014 Aug;13(8):767-76.
• [8] Coronary circulation responses to binodenoson, a selective adenosine A2A receptor agonist. Am J Cardiol. 2007 Jun 1;99(11):1507-12.
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3290).
• [10] 2-Amino-5-benzoyl-4-phenylthiazoles: Development of potent and selective adenosine A1 receptor antagonists. Bioorg Med Chem. 2010 Mar 15;18(6):2195-2203.
• [11] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [12] Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2746-53.
• [13] Novel pharmacological targets for the treatment of Parkinson's disease. Nat Rev Drug Discov. 2006 Oct;5(10):845-54.
• [14] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [15] Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor. PLoS One. 2015; 10(3): e0122197.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] New Drugs/Drug News. P T. 2013 November; 38(11): 667-672.
• [18] PDE10A Inhibitors-Clinical Failure or Window Into Antipsychotic Drug Action?. Front Neurosci. 2021 Jan 20;14:600178.
• [19] Massive schizophrenia genomics study offers new drug directions. Nat Rev Drug Discov. 2014 Sep;13(9):641-2.
• [20] Synaptic synopsis. SciBX 6(41); doi:10.1038/scibx.2013.1153. Oct. 24, 2013
• [21] Discovery of clinical candidate 1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone (AMG 579), a potent, selective, and efficacious inhibitor of phosphodiesterase10A (PDE10A). J Med Chem. 2014 Aug 14;57(15):6632-41.
• [22] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.