Details of the Drug Combination

General Information of Drug Combination (ID: DCZ3Q2K)

• Drug Combination Name: Trihexyphenidyl + Mesalazine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Trihexyphenidyl (DMB19L8): Small molecular drug
  Mesalazine (DMOL5IU): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.78
  Bliss Independence Score: 8.78
  Loewe Additivity Score: 22.6
  LHighest Single Agent (HSA) Score: 22.61

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Trihexyphenidyl

Disease Entry	ICD 11	Status	REF
Dystonia	8A02	Approved	[2]
Parkinson disease	8A00.0	Approved	[2]
Parkinsonian disorder	N.A.	Approved	[3]
Postencephalitic Parkinson disease	N.A.	Approved	[3]
Obesity	5B81	Investigative	[4]

Trihexyphenidyl Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M1 (CHRM1)	TTZ9SOR	ACM1_HUMAN	Antagonist	[9]
Adrenergic receptor beta-3 (ADRB3)	TTMXGCW	ADRB3_HUMAN	Agonist	[4]

Trihexyphenidyl Interacts with 13 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[10]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[10]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[10]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[10]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[10]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[10]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[10]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6)	OT1SLUZH	TSG6_HUMAN	Increases Expression	[10]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[10]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[10]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[10]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Increases Response To Substance	[11]

Indication(s) of Mesalazine

Disease Entry	ICD 11	Status	REF
Diverticulitis	N.A.	Approved	[5]
Proctitis	DB33.Z	Approved	[6]
Ulcerative colitis	DD71	Approved	[7]
Ulcerative proctosigmoiditis	N.A.	Approved	[8]

Mesalazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Inhibitor	[12]

Mesalazine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[13]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[14]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[14]

Mesalazine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[15]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [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: 7315).
• [3] Trihexyphenidyl FDA Label
• [4] Obesity: pathophysiology and clinical management. Curr Med Chem. 2009;16(4):506-21.
• [5] Colonic diverticular disease. Nat Rev Dis Primers. 2020 Mar 26;6(1):20.
• [6] Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository. Digestion. 2018;97(1):59-63.
• [7] 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: 4655).
• [8] Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis. J Crohns Colitis. 2021 Jul 5;15(7):1184-1196.
• [9] The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic dr... Psychopharmacology (Berl). 2009 Apr;203(2):295-301.
• [10] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [11] Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly. Am J Geriatr Psychiatry. 2008 Feb;16(2):116-24. doi: 10.1097/JGP.0b013e31815aff75.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] Transport studies with 5-aminosalicylate. Eur J Clin Pharmacol. 2006 Oct;62(10):871-5.
• [14] Role of organic anion-transporting polypeptides for cellular mesalazine (5-aminosalicylic acid) uptake. Drug Metab Dispos. 2011 Jun;39(6):1097-102.
• [15] NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Z Gastroenterol. 2008 Mar;46(3):259-65.