Details of the Drug Combination

General Information of Drug Combination (ID: DCS5T54)

• Drug Combination Name: Cortisone Acetate + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Cortisone Acetate (DMG8K57): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 36.9
  Bliss Independence Score: 37.56
  Loewe Additivity Score: 12.01
  LHighest Single Agent (HSA) Score: 21.01

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	[9]

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	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[11]
Corticosteroid 11-beta-dehydrogenase 1 (HSD11B1)	DEZDRQO	DHI1_HUMAN	Metabolism	[12]
Corticosteroid 11-beta-dehydrogenase 2 (HSD11B2)	DEDH7FP	DHI2_HUMAN	Metabolism	[12]
Short-chain dehydrogenase/reductase retSDR4 (DHRS7)	DEEXSKI	DHRS7_HUMAN	Metabolism	[13]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[4]
High-risk myelofibrosis	2A20.2	Approved	[5]
Myelofibrosis	2A22	Approved	[3]
Myeloproliferative neoplasm	2A20	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[7]
Pancreatic cancer	2C10	Phase 3	[5]
Atopic dermatitis	EA80	Phase 1/2	[8]
Vitiligo	ED63.0	Phase 1/2	[8]

Ruxolitinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[14]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[14]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[15]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[16]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[16]

Ruxolitinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[17]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] Cortisone acetate FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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: 5688).
• [6] Ruxolitinib FDA Label
• [7] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] 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.
• [11] 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.
• [12] Comparative enzymology of 11beta-hydroxysteroid dehydrogenase type 1 from six species. J Mol Endocrinol. 2005 Aug;35(1):89-101.
• [13] Human DHRS7, promising enzyme in metabolism of steroids and retinoids? J Steroid Biochem Mol Biol. 2016 Jan;155(Pt A):112-9.
• [14] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [15] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [16] The Use of Anti-Inflammatory Drugs in the Treatment of People With Severe Coronavirus Disease 2019 (COVID-19): The Perspectives of Clinical Immunologists From China. Clin Immunol. 2020 May;214:108393.
• [17] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.