Details of the Drug Combination

General Information of Drug Combination (ID: DCYBIVV)

• Drug Combination Name: Calcipotriol + Betamethasone
• Indication: Plaque Psoriasis; Status: Phase 4 [1]
• Component Drugs:
  Calcipotriol (DM03CP7): Small molecular drug
  Betamethasone (DMAHJEF): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Calcipotriol

Disease Entry	ICD 11	Status	REF
Psoriasis	EA90	Approved	[2]
Psoriasis vulgaris	EA90	Approved	[3]

Calcipotriol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Vitamin D3 receptor (VDR)	TTK59TV	VDR_HUMAN	Antagonist	[6]

Calcipotriol Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (CYP24A1)	OTG2T749	CP24A_HUMAN	Increases Expression	[7]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[8]
Involucrin (IVL)	OT4VPNGY	INVO_HUMAN	Decreases Expression	[9]
Keratin, type I cytoskeletal 16 (KRT16)	OTGA0EQN	K1C16_HUMAN	Decreases Expression	[9]
Keratin, type I cytoskeletal 10 (KRT10)	OTSVRD3Q	K1C10_HUMAN	Decreases Expression	[9]
Filaggrin (FLG)	OTE9QDV6	FILA_HUMAN	Decreases Expression	[9]
Cytochrome P450 7A1 (CYP7A1)	OT8Z5KLD	CP7A1_HUMAN	Decreases Expression	[8]
Keratin, type I cytoskeletal 17 (KRT17)	OT6Y1DPK	K1C17_HUMAN	Decreases Expression	[9]
Beclin-1 (BECN1)	OT4X293M	BECN1_HUMAN	Increases Expression	[10]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[8]

Indication(s) of Betamethasone

Disease Entry	ICD 11	Status	REF
Acute adrenal insufficiency	N.A.	Approved	[4]
Addison disease	5A74.0	Approved	[4]
Allergic rhinitis	CA08.0	Approved	[4]
Angioedema	4A00.15	Approved	[4]
Aspiration pneumonitis	N.A.	Approved	[4]
Autoimmune haemolytic anaemia	3A20	Approved	[4]
Bursitis	N.A.	Approved	[4]
Cerebral edema	8D60.1	Approved	[4]
Congenital adrenal hyperplasia	5A71.01	Approved	[4]
Crohn disease	DD70	Approved	[4]
Dermatitis herpetiformis	EB44	Approved	[4]
Diamond-Blackfan anemia	N.A.	Approved	[4]
Disorder of orbital region	N.A.	Approved	[4]
Epicondylitis	N.A.	Approved	[4]
Erythema multiforme	N.A.	Approved	[4]
Exanthem	N.A.	Approved	[4]
Granuloma annulare	N.A.	Approved	[4]
Inflammation	1A00-CA43.1	Approved	[5]
Inflammatory bowel disease	DD72	Approved	[4]
Miliary tuberculosis	N.A.	Approved	[4]
Multiple sclerosis	8A40	Approved	[4]
Mycosis fungoides	2B01	Approved	[4]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[4]
Psoriasis	EA90	Approved	[4]
Psoriatic arthritis	FA21	Approved	[4]
Rheumatic heart disease	N.A.	Approved	[4]
Sarcoidosis	4B20.5	Approved	[4]
Scalp dermatosis	N.A.	Approved	[4]
Serum sickness	N.A.	Approved	[4]
Severe asthma	CA23	Approved	[4]
Skin disease	EA00-EM0Z	Approved	[4]
Systemic lupus erythematosus	4A40.0	Approved	[4]
Tinea corporis	1F28.Y	Approved	[4]
Tinea cruris	1F28.3	Approved	[4]
Acquired thrombocytopenia	N.A.	Investigative	[4]
Asthma	CA23	Investigative	[4]
Beta-thalassemia major	N.A.	Investigative	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]
Follicular lymphoma	2A80	Investigative	[4]
Rheumatoid arthritis	FA20	Investigative	[4]
Synovitis	N.A.	Investigative	[4]
Tinea pedis	1F28.2	Investigative	[4]
Trichinellosis	N.A.	Investigative	[4]

Betamethasone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Agonist	[12]

Betamethasone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]

Betamethasone Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Frataxin, mitochondrial (FXN)	OTE9U09A	FRDA_HUMAN	Increases Expression	[14]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases Activity	[15]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[15]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[11]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[11]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[11]
Early growth response protein 1 (EGR1)	OTCP6XGZ	EGR1_HUMAN	Affects Expression	[16]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Increases Metabolism	[17]

References

• [1] ClinicalTrials.gov (NCT03020199) Study of the Efficacy of Early Intervention With Secukinumab 300 mg s.c. Compared to Narrow-band UVB in Patients With New-onset Moderate to Severe Plaque Psoriasis
• [2] Calcipotriol and psoriasis. Int J Dermatol. 1992 Aug;31(8):549-50.
• [3] 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: 2778).
• [4] Betamethasone FDA Label
• [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: 7061).
• [6] Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008 Apr;9(4):345-59.
• [7] Actions of Vitamin D3, analogs on human prostate cancer cell lines: comparison with 1,25-dihydroxyvitamin D3. Endocrinology. 1995 Jan;136(1):20-6.
• [8] Adaptive homeostasis of the vitamin D-vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity. Toxicol Appl Pharmacol. 2019 Jan 1;362:150-158. doi: 10.1016/j.taap.2018.11.002. Epub 2018 Nov 10.
• [9] Effects of 1 alpha,25-dihydroxy-vitamin D3 and calcipotriol on organotypic cultures of outer root sheath cells: a potential model to evaluate antipsoriatic drugs. Arch Dermatol Res. 1993;285(7):402-9. doi: 10.1007/BF00372133.
• [10] Calcipotriol induces autophagy in HeLa cells and keratinocytes. J Invest Dermatol. 2011 Apr;131(4):990-3. doi: 10.1038/jid.2010.423. Epub 2011 Jan 13.
• [11] Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
• [12] The cannabinoid CB2 receptor inverse agonist JTE-907 suppresses spontaneous itch-associated responses of NC mice, a model of atopic dermatitis. Eur J Pharmacol. 2006 Aug 7;542(1-3):179-83.
• [13] Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803.
• [14] Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia. PLoS One. 2013;8(2):e55940.
• [15] Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol. 2004 Sep;151(3):397-406. doi: 10.1530/eje.0.1510397.
• [16] [Steroid drugs and GM-CSF modulates activity of Egr-1 in glioma cells]. Cir Cir. 2013 Jan-Feb;81(1):3-13.
• [17] Metabolism of synthetic steroids by the human placenta. Placenta. 2007 Jan;28(1):39-46.