Details of the Drug

General Information of Drug (ID: DMZI2UF)

• Drug Name: Sulphadoxine
• Synonyms: 2447-57-6; Sulforthomidine; Fanasil; Sulphormethoxine; 4-amino-N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide; Sulfadoxinum; Sulfadoxina; Sulfadoxin; Fanzil; Solfadossina; Ro 4-4393; Solfadossina [DCIT]; Sulfadoxinum [INN-Latin]; Sulfadoxina [INN-Spanish]; 4-Sulfanilamido-5,6-dimethoxypyrimidine; 4-Amino-N-(5,6-dimethoxy-4-pyrimidinyl)benzenesulfonamide; Benzenesulfonamide, 4-amino-N-(5,6-dimethoxy-4-pyrimidinyl)-; WR 4873; N'-(5,6-Dimethoxy-4-pyrimidyl)sulfanilamide; UNII-88463U4SM5; Orthosulfin; Sulformethoxine; Sulformetoxine; Sulphormetoxin; Sulphorthodimethoxine; WR 4073; Ro-4-4393; Sanasil: Sulfadoxine: Sulformetoxin; Sulfadoxine (JAN/USP/INN); Sulfadoxine [USAN:INN:BAN:JAN]; N1-(5,6-Dimethoxy-4-pyrimidinyl)sulfanilamide; N(sup 1)-(5,6-Dimethoxy-4-pyrimidinyl)sulfanilamide; 4-amino-N-[5,6-bis(methyloxy)pyrimidin-4-yl]benzenesulfonamide; 6-(4-Aminobenzenesulfonamido)-4,5-dimethoxypyrimidine; RS-1653

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 310.33
  Logarithm of the Partition Coefficient (xlogp); 0.7
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• ADMET Property: MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 80.55843 micromolar/kg/day [2]
• Chemical Identifiers:
  Formula: C12H14N4O4S
  IUPAC Name: 4-amino-N-(5,6-dimethoxypyrimidin-4-yl)benzenesulfonamide
  Canonical SMILES: COC1=C(N=CN=C1OC)NS(=O)(=O)C2=CC=C(C=C2)N
  InChI: InChI=1S/C12H14N4O4S/c1-19-10-11(14-7-15-12(10)20-2)16-21(17,18)9-5-3-8(13)4-6-9/h3-7H,13H2,1-2H3,(H,14,15,16)
  InChIKey: PJSFRIWCGOHTNF-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 17134
  ChEBI ID: CHEBI:9329
  CAS Number: 2447-57-6
  DrugBank ID: DB01299
  TTD ID: D07PAO

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Dihydropteroate synthetase (Bact folP)	TT4ILYC	DHPS_ECOLI	Binder	[1]
Monoamine oxidase type B (MAO-B)	TTGP7BY	AOFB_HUMAN	Inhibitor	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Malaria
• ICD Disease Classification: 1F40-1F45

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Monoamine oxidase type B (MAO-B)	DTT	MAOB	2.65E-02	1.12E-02	0.07

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Sulphadoxine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[4]
Insulin-glulisine	DMQI0FU	Moderate	Increased risk of hypoglycemia by the combination of Sulphadoxine and Insulin-glulisine.	Acute diabete complication [5A2Y]	[5]
Insulin-aspart	DMX7V28	Moderate	Increased risk of hypoglycemia by the combination of Sulphadoxine and Insulin-aspart.	Acute diabete complication [5A2Y]	[6]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[7]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[8]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Cannabidiol.	Epileptic encephalopathy [8A62]	[9]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[10]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[11]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Sulphadoxine and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[12]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[13]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Idelalisib.	Mature B-cell leukaemia [2A82]	[14]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Sulphadoxine and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[9]
Insulin-detemir	DMOA4VW	Moderate	Increased risk of hypoglycemia by the combination of Sulphadoxine and Insulin-detemir.	Type-1/2 diabete [5A10-5A11]	[5]
Insulin degludec	DMPL395	Moderate	Increased risk of hypoglycemia by the combination of Sulphadoxine and Insulin degludec.	Type-1/2 diabete [5A10-5A11]	[5]

References

• [1] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [2] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [3] Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility. Jpn J Pharmacol. 2002 Feb;88(2):174-82.
• [4] Cerner Multum, Inc. "Australian Product Information.".
• [5] Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7. [PMID: 11678792]
• [6] Asplund K, Wiholm BE, Lithner F "Glibenclamide-associated hypoglycaemia: a report on 57 cases." Diabetologia 24 (1983): 412-7. [PMID: 6411511]
• [7] Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
• [8] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [10] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [11] Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
• [12] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [13] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
• [14] Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.