Details of the Drug Combination

General Information of Drug Combination (ID: DC307RC)

• Drug Combination Name: Cortisone Acetate + cortisone
• Indication: Addison Disease; Status: Phase 1 [1]
• Component Drugs:
  Cortisone Acetate (DMG8K57): Small molecular drug
  cortisone (DMU5QZX): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cortisone Acetate

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[2]
Acute adrenal insufficiency	N.A.	Approved	[2]
Addison disease	5A74.0	Approved	[2]
Advanced cancer	2A00-2F9Z	Approved	[2]
Allergic rhinitis	CA08.0	Approved	[2]
Angioedema	4A00.15	Approved	[2]
Aspiration pneumonitis	N.A.	Approved	[2]
Autoimmune haemolytic anaemia	3A20	Approved	[2]
Blepharoconjunctivitis	N.A.	Approved	[2]
Bursitis	N.A.	Approved	[2]
Cerebral edema	8D60.1	Approved	[2]
Congenital adrenal hyperplasia	5A71.01	Approved	[2]
Corneal abrasion	NA06.4	Approved	[2]
Corneal ulcer	9A76	Approved	[2]
Crohn disease	DD70	Approved	[2]
Dermatitis herpetiformis	EB44	Approved	[2]
Diamond-Blackfan anemia	N.A.	Approved	[2]
Disorder of orbital region	N.A.	Approved	[2]
Epicondylitis	N.A.	Approved	[2]
Erythema multiforme	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Gingival disorder	N.A.	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[2]
Keratitis	N.A.	Approved	[2]
Malignant otitis externa caused by Pseudomonas aeruginosa	N.A.	Approved	[2]
Miliary tuberculosis	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Proctitis	DB33.Z	Approved	[2]
Psoriasis	EA90	Approved	[2]
Psoriatic arthritis	FA21	Approved	[2]
Rheumatic heart disease	N.A.	Approved	[2]
Rosacea	ED90.0	Approved	[2]
Sarcoidosis	4B20.5	Approved	[2]
Serum sickness	N.A.	Approved	[2]
Severe asthma	CA23	Approved	[2]
Skin disease	EA00-EM0Z	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Tinea corporis	1F28.Y	Approved	[2]
Tinea cruris	1F28.3	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]
Acquired thrombocytopenia	N.A.	Investigative	[2]
Asthma	CA23	Investigative	[2]
Beta-thalassemia major	N.A.	Investigative	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Follicular lymphoma	2A80	Investigative	[2]
Iridocyclitis	N.A.	Investigative	[2]
Rheumatoid arthritis	FA20	Investigative	[2]
Synovitis	N.A.	Investigative	[2]
Tinea pedis	1F28.2	Investigative	[2]
Trichinellosis	N.A.	Investigative	[2]
Uveitis	9A96.Z	Investigative	[2]

Cortisone Acetate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid hormone receptor ERR (ESRR)	TTP3UTW	ERR1_HUMAN; ERR2_HUMAN; ERR3_HUMAN	Modulator	[5]

Cortisone Acetate Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[7]
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	DEZDRQO	DHI1_HUMAN	Metabolism	[8]
Corticosteroid 11-beta-dehydrogenase 2 (HSD11B2)	DEDH7FP	DHI2_HUMAN	Metabolism	[8]
Short-chain dehydrogenase/reductase retSDR4 (DHRS7)	DEEXSKI	DHRS7_HUMAN	Metabolism	[9]

Indication(s) of cortisone

Disease Entry	ICD 11	Status	REF
Atopic dermatitis	EA80	Approved	[4]

cortisone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]

cortisone Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[11]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[11]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Activity	[12]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[12]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Increases Expression	[13]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Increases Chemical Synthesis	[14]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Increases Metabolism	[15]
Dehydrogenase/reductase SDR family member 7 (DHRS7)	OTV729DT	DHRS7_HUMAN	Increases Reduction	[16]

References

• [1] ClinicalTrials.gov (NCT02096510) Ultradian Subcutaneous Hydrocortisone Infusion in Addison Disease and Congenital Adrenal Hyperplasia
• [2] Cortisone acetate FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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: 5171).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Prediction of tacrolimus metabolism and dosage requirements based on CYP3A4 phenotype and CYP3A5(*)3 genotype in Chinese renal transplant recipients. Acta Pharmacol Sin. 2016 Apr;37(4):555-60.
• [7] Comparative pharmacokinetics and metabolism studies in lean and diet- induced obese mice: an animal efficacy model for 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors. Drug Metab Lett. 2011 Jan;5(1):55-63.
• [8] Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six species. J Mol Endocrinol. 2005 Aug;35(1):89-101.
• [9] Human DHRS7, promising enzyme in metabolism of steroids and retinoids? J Steroid Biochem Mol Biol. 2016 Jan;155(Pt A):112-9.
• [10] Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803.
• [11] Effect of PFOS on glucocorticoid-induced changes in human decidual stromal cells in the first trimester of pregnancy. Reprod Toxicol. 2016 Aug;63:142-50.
• [12] The human mineralocorticoid receptor only partially differentiates between different ligands after expression in fission yeast. FEMS Yeast Res. 2005 Apr;5(6-7):627-33. doi: 10.1016/j.femsyr.2004.12.007.
• [13] A cardiac-specific robotized cellular assay identified families of human ligands as inducers of PGC-1 expression and mitochondrial biogenesis. PLoS One. 2012;7(10):e46753. doi: 10.1371/journal.pone.0046753. Epub 2012 Oct 3.
• [14] Species-specific differences in the inhibition of human and zebrafish 11beta-hydroxysteroid dehydrogenase 2 by thiram and organotins. Toxicology. 2012 Nov 15;301(1-3):72-8.
• [15] Local amplification of glucocorticoids by 11 beta-hydroxysteroid dehydrogenase type 1 promotes macrophage phagocytosis of apoptotic leukocytes. J Immunol. 2006 Jun 15;176(12):7605-11. doi: 10.4049/jimmunol.176.12.7605.
• [16] Biochemical properties of human dehydrogenase/reductase (SDR family) member 7. Chem Biol Interact. 2014 Jan 25;207:52-7. doi: 10.1016/j.cbi.2013.11.003. Epub 2013 Nov 16.