Details of the Drug Combination

General Information of Drug Combination (ID: DCTT9F0)

• Drug Combination Name: ABIRATERONE + Prednisone
• Indication: Hormone-Resistant Prostate Cancer; Status: Phase 1 [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Prednisone (DM2HG4X): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABIRATERONE

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

ABIRATERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-monooxygenase (S17AH)	TTRA5BZ	CP17A_HUMAN	Modulator	[7]

ABIRATERONE Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Activity	[8]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[9]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[11]

Indication(s) of Prednisone

Disease Entry	ICD 11	Status	REF
Acute asthma	CA23	Approved	[3]
Addison disease	5A74.0	Approved	[3]
Allergic rhinitis	CA08.0	Approved	[3]
Angioedema	4A00.15	Approved	[3]
Autoimmune haemolytic anaemia	3A20	Approved	[3]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[3]
Congenital adrenal hyperplasia	5A71.01	Approved	[3]
Crohn disease	DD70	Approved	[3]
Dermatitis herpetiformis	EB44	Approved	[3]
Diamond-Blackfan anemia	N.A.	Approved	[3]
Epicondylitis	N.A.	Approved	[3]
Erythema multiforme	N.A.	Approved	[3]
Inflammation	1A00-CA43.1	Approved	[4]
Inflammatory bowel disease	DD72	Approved	[3]
Multiple sclerosis	8A40	Approved	[3]
Mycosis fungoides	2B01	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Polymyalgia rheumatica	N.A.	Approved	[3]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[3]
Prostate adenocarcinoma	N.A.	Approved	[3]
Psoriasis	EA90	Approved	[3]
Psoriatic arthritis	FA21	Approved	[3]
Rheumatic heart disease	N.A.	Approved	[3]
Sarcoidosis	4B20.5	Approved	[3]
Serum sickness	N.A.	Approved	[3]
Skin disease	EA00-EM0Z	Approved	[3]
Small lymphocytic lymphoma	2A82.0	Approved	[3]
Systemic lupus erythematosus	4A40.0	Approved	[3]
Atopic dermatitis	EA80	Phase 1	[5]
Eczema	EA80-EA89	Phase 1	[5]
Acquired thrombocytopenia	N.A.	Investigative	[3]
Asthma	CA23	Investigative	[3]
Beta-thalassemia major	N.A.	Investigative	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[6]
Follicular lymphoma	2A80	Investigative	[3]
Rheumatoid arthritis	FA20	Investigative	[3]
Trichinellosis	N.A.	Investigative	[3]

Prednisone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Agonist	[14]

Prednisone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]

Prednisone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[16]

Prednisone Interacts with 20 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Secretion	[17]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Activity	[18]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Activity	[19]
Tissue-type plasminogen activator (PLAT)	OTQPDNAB	TPA_HUMAN	Increases Expression	[20]
Antithrombin-III (SERPINC1)	OTDFATG0	ANT3_HUMAN	Increases Expression	[21]
Alpha-2-macroglobulin (A2M)	OTFTX90K	A2MG_HUMAN	Decreases Expression	[21]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Expression	[22]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Decreases Expression	[23]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Expression	[24]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[24]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[22]
Glycogen phosphorylase, muscle form (PYGM)	OTWLVWTV	PYGM_HUMAN	Decreases Expression	[25]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Decreases Expression	[26]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[27]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Increases Expression	[27]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Increases Expression	[27]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[27]
Eotaxin (CCL11)	OT3BIFPK	CCL11_HUMAN	Decreases Expression	[26]
C-C motif chemokine 13 (CCL13)	OTNX0JD0	CCL13_HUMAN	Decreases Expression	[26]
Glutathione S-transferase Mu 1 (GSTM1)	OTSBF2MO	GSTM1_HUMAN	Affects Response To Substance	[13]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Castration Levels of Testosterone	DC81FZT	N. A.	Phase 2	[28]

References

• [1] ClinicalTrials.gov (NCT01503229) Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
• [2] 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: 6745).
• [3] Prednisone FDA Label
• [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: 7096).
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Certain corticosteroid could improve severe COVID-19, say researchers. May 20, 2020
• [7] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [8] A fission yeast-based test system for the determination of IC50 values of anti-prostate tumor drugs acting on CYP21. J Enzyme Inhib Med Chem. 2006 Oct;21(5):547-56.
• [9] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [10] Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer. JCI Insight. 2018 Sep 6;3(17):e121497. doi: 10.1172/jci.insight.121497. eCollection 2018 Sep 6.
• [11] Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23.
• [12] Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells. J Steroid Biochem Mol Biol. 1995 Aug;54(3-4):147-53. doi: 10.1016/0960-0760(95)00128-m.
• [13] Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood. 2005 Jun 15;105(12):4752-8. doi: 10.1182/blood-2004-11-4544. Epub 2005 Feb 15.
• [14] Cytochromes P450 (CYP) in the Poeciliopsis lucida hepatocellular carcinoma cell line (PLHC-1): dose- and time-dependent glucocorticoid potentiation of CYP1A induction without induction of CYP3A. ArchBiochem Biophys. 1996 May 1;329(1):113-22.
• [15] Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803.
• [16] Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction. Expert Opin Drug Metab Toxicol. 2014 Mar;10(3):425-35.
• [17] Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux. Toxicol Appl Pharmacol. 2012 May 1;260(3):294-302. doi: 10.1016/j.taap.2012.03.008. Epub 2012 Mar 23.
• [18] Identification of chemical compounds that induce HIF-1alpha activity. Toxicol Sci. 2009 Nov;112(1):153-63.
• [19] Differential regulation of the human MRP2 and MRP3 gene expression by glucocorticoids. J Steroid Biochem Mol Biol. 2005 Aug;96(3-4):229-34. doi: 10.1016/j.jsbmb.2005.03.004.
• [20] Relation between long-term steroid treatment after heart transplantation, hypofibrinolysis and myocardial microthrombi generation. J Heart Lung Transplant. 1999 Jul;18(7):693-700. doi: 10.1016/s1053-2498(99)00021-2.
• [21] Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report. Am J Ther. 2001 Mar-Apr;8(2):97-107. doi: 10.1097/00045391-200103000-00004.
• [22] Cytokine abnormalities in a patient with eosinophilic fasciitis. Ann Allergy Asthma Immunol. 2003 Apr;90(4):452-5. doi: 10.1016/S1081-1206(10)61832-7.
• [23] Prednisone effects on neurochemistry and behavior. Preliminary findings. Arch Gen Psychiatry. 1990 Oct;47(10):963-8. doi: 10.1001/archpsyc.1990.01810220079010.
• [24] Immune responses in autoimmune hepatitis: effect of prednisone and azathioprine treatment: case report. Int J Med Sci. 2009 Jun 30;6(4):177-83. doi: 10.7150/ijms.6.177.
• [25] Muscle glycogen of steroid myopathy patients. J Neurol Sci. 1996 Mar;136(1-2):192-5. doi: 10.1016/0022-510x(95)00331-u.
• [26] Alterations in eotaxin, monocyte chemoattractant protein-4, interleukin-5, and interleukin-13 after systemic steroid treatment for nasal polyps. Otolaryngol Head Neck Surg. 2004 Nov;131(5):585-9. doi: 10.1016/j.otohns.2004.05.028.
• [27] Glucocorticoids induce G1 arrest of lymphoblastic cells through retinoblastoma protein Rb1 dephosphorylation in childhood acute lymphoblastic leukemia in vivo. Cancer Biol Ther. 2004 May;3(5):470-6. doi: 10.4161/cbt.3.5.838. Epub 2004 May 9.
• [28] ClinicalTrials.gov (NCT02703623) Abiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer