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

General Information of Drug (ID: DMB7EIN)

• Drug Name: PF-915275 Drug Info
• Synonyms: PF-915275; 857290-04-1; PF 915275; UNII-388927163B; N-(6-aminopyridin-2-yl)-4'-cyanobiphenyl-4-sulfonamide; 388927163B; ZESFDAKNYJQYKO-UHFFFAOYSA-N; SCHEMBL4384483; CHEMBL495841; CTK5F5674; BDBM29864; DTXSID00235037; MolPort-023-276-737; KS-00001D9U; BCP28049; ZINC40955326; AKOS024457530; CS-5559; N-(Pyridin-2-yl) arylsulfonamide, 26; NCGC00370811-01; HY-18056; RT-015014; KB-274983; B7346; N-(6-Aminopyridin-2-yl)4'-cyanobiphenyl-4-sulfonamide; N-(6-Amino-2-pyridinyl)-4'-cyano-[1,1'-biphenyl]-4-sulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Discontinued in Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 23725123
  CAS Number: CAS 857290-04-1
  TTD Drug ID: DMB7EIN

Molecule-Related Drug Atlas

Drug(s) Targeting Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GLYCYRRHIZIN	DM8M2N3	Influenza virus infection	1E30-1E32	Phase 3	[4]
BVT.2733	DM6RUKX	Lupus	4A40	Phase 3	[5]
INCB13739	DMLQ3PO	Type-2 diabetes	5A11	Phase 2a	[6]
URSOLIC ACID	DM4SOAW	Metabolic syndrome x	5C50-5D2Z	Phase 2	[7]
JTT-654	DM50M2R	Type-2 diabetes	5A11	Phase 2	[8]
RG-4929	DMT4QRD	Metabolic disorder	5C50-5D2Z	Phase 2	[8]
BMS-770767	DMTVGY7	Hypercholesterolaemia	5C80.0	Phase 2	[8]
UE-2343	DMIERPK	Alzheimer disease	8A20	Phase 2	[9]
AZD-4017	DML9M5S	Ocular hypertension	9C61.01	Phase 2	[8]
Xanamem	DM580GT	Alzheimer disease	8A20	Phase 1/2	[10]

Drug(s) Affected By 11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[11]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[12]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[11]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[13]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[14]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[15]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[16]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[12]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	TTN7BL9	DHI1_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_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 800025590)
• [2] N-(Pyridin-2-yl) arylsulfonamide inhibitors of 11beta-hydroxysteroid dehydrogenase type 1: Discovery of PF-915275. Bioorg Med Chem Lett. 2009 Jul 1;19(13):3493-7.
• [3] Induction of 11-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells. Mol Endocrinol. 2013 Feb;27(2):192-202. doi: 10.1210/me.2012-1247. Epub 2012 Dec 28.
• [4] Discovery of novel dual functional agent as PPARgamma agonist and 11beta-HSD1 inhibitor for the treatment of diabetes. Bioorg Med Chem. 2009 Aug 1;17(15):5722-32.
• [5] Selective inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 improves hepatic insulin sensitivity in hyperglycemic mice strains. Endocrinology. 2003 Nov;144(11):4755-62.
• [6] Incyte's Selective Oral Inhibitor Of 11beta-HSD1 Demonstrates Improvements In Insulin Sensitivity And Lowers Cholesterol Levels In Type 2 Diabetics. Incyte. 2008.
• [7] 11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational a... Bioorg Med Chem. 2010 Feb 15;18(4):1507-15.
• [8] New Therapeutic Strategies for Type 2 Diabetes: Small Molecule Approaches. 2012. Chapter 5. Page(131).
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Selection and early clinical evaluation of the brain-penetrant 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor UE2343 (Xanamem?). Br J Pharmacol. 2017 Mar;174(5):396-408.
• [11] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [12] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [13] Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months. Antivir Ther. 2009;14(8):1089-100. doi: 10.3851/IMP1457.
• [14] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [15] Testosterone stimulates adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in a depot-specific manner in children. J Clin Endocrinol Metab. 2010 Jul;95(7):3300-8.
• [16] Role of calcitriol and cortisol on human adipocyte proliferation and oxidative and inflammatory stress: a microarray study. J Nutrigenet Nutrigenomics. 2008;1(1-2):30-48. doi: 10.1159/000109873. Epub 2007 Oct 16.
• [17] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [18] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.