Details of the Drug Combination

General Information of Drug Combination (ID: DC62OSK)

• Drug Combination Name: Terbutaline + Danazol
• Indication: Immune Thrombocytopenia; Status: Phase 2 [1]
• Component Drugs:
  Terbutaline (DMD4381): Small molecular drug
  Danazol (DML8KTN): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Terbutaline

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Approved	[2]
Bronchitis	CA20	Approved	[3]
Pulmonary emphysema	CA21.Z	Approved	[3]
Severe asthma	CA23	Approved	[3]
Pruritus	EC90	Investigative	[3]

Terbutaline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-2 (ADRB2)	TT2CJVK	ADRB2_HUMAN	Agonist	[6]

Terbutaline Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]

Terbutaline Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Response To Substance	[8]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[9]
Pulmonary surfactant-associated protein B (SFTPB)	OTOHS07E	PSPB_HUMAN	Increases Expression	[10]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Activity	[11]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Increases Expression	[12]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Increases Expression	[12]

Indication(s) of Danazol

Disease Entry	ICD 11	Status	REF
Menorrhagia	GA20.50	Approved	[4]
Breast cancer	2C60-2C65	Phase 2	[4]
Breast fibrocystic disease	N.A.	Investigative	[5]
Endometriosis	GA10	Investigative	[5]

Danazol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Antagonist	[13]

Danazol Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[14]
Plasma protease C1 inhibitor (SERPING1)	OT6CVN45	IC1_HUMAN	Increases Expression	[15]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[16]

References

• [1] ClinicalTrials.gov (NCT04481282) The Combination of Terbutaline and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
• [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: 560).
• [3] Terbutaline 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: 6942).
• [5] Danazol FDA Label
• [6] Evaluation of a new oral beta2-adrenoceptor stimulant bronchodilator, terbutaline. Pharmacology. 1975;13(3):201-11.
• [7] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [8] Beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus. Pediatr Crit Care Med. 2006 Jan;7(1):15-8. doi: 10.1097/01.pcc.0000194010.63115.a2.
• [9] Beta-adrenoceptor activation-induced placental prorenin secretion is mediated by increased renin messenger RNA and protein synthesis. Mol Pharmacol. 1997 Feb;51(2):201-8. doi: 10.1124/mol.51.2.201.
• [10] Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung. J Clin Invest. 1989 Apr;83(4):1191-7. doi: 10.1172/JCI114000.
• [11] Activation of beta(2)-adrenoceptor prevents shiga toxin 2-induced TNF-alpha gene transcription. J Am Soc Nephrol. 2001 Nov;12(11):2288-2299. doi: 10.1681/ASN.V12112288.
• [12] Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol. 1999 Mar 1;95(1-2):165-73. doi: 10.1016/s0165-5728(99)00011-9.
• [13] Danazol suppression of luteinizing hormone in the rat: evidence for mediation by both androgen and estrogen receptors. Proc Soc Exp Biol Med. 1990 May;194(1):54-7.
• [14] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [15] Guillain-Barr syndrome following danazol and corticosteroid therapy for hereditary angioedema. Am J Med. 1985 Jul;79(1):111-4. doi: 10.1016/0002-9343(85)90553-4.
• [16] High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.