Details of the Drug

General Information of Drug (ID: DME1LQN)

• Drug Name: Streptomycin
• Synonyms: Agrept; Agrimycin; Gerox; Neodiestreptopab; SRY; Strepcen; Streptomicina; Streptomycine; Streptomycinum; Streptomyzin; Liposomal Streptomycin; Streptomicina [Italian]; Streptomycin A; Streptomycin A sulfate; Streptomycin Sesquisulfate Hydrate; Streptomycin sulfate; Streptomycin sulphate; Streptomyzin [German]; Agrept (TN); Estreptomicina [INN-Spanish]; Hokko-mycin; Plantomycin (TN); Rimosidin (TN); Streptomycin & EEP; Streptomycin & Propolis; Streptomycin (INN); Streptomycin (TN); Streptomycin [INN:BAN]; Streptomycin, Sulfate Salt; AS-50 (TN); STREPTOMYCIN SULFATE (2:3) SALT; Agri-mycin-17 (TN); O-2-Deoxy-2-(methylamino)-.alpha.-L-glucopyranosyl-(1->2)-O-5-deoxy-3-C-formyl-.alpha.-L-lyxofuranosyl-(1->4)-N,N'-bis(aminoiminomethyl)-D-streptamine and Liposome; N,N'''-[(1R,2R,3S,4R,5R,6S)-4-{5-deoxy-2-O-[2-deoxy-2-(methylamino)-alpha-L-glucopyranosyl]-3-C-formyl-alpha-L-lyxofuranosyloxy}-2,5,6-trihydroxycyclohexane-1,3-diyl]diguanidine; N,N'''-[(1R,2R,3S,4R,5R,6S)-4-({5-deoxy-2-O-[2-deoxy-2-(methylamino)-alpha-L-glucopyranosyl]-3-C-formyl-alpha-L-lyxofuranosyl}oxy)-2,5,6-trihydroxycyclohexane-1,3-diyl]diguanidine; 2,4-Diguanidino-3,5,6-trihydroxycyclohexyl 5-deoxy-2-O-(2-deoxy-2-methylamino-alpha-L-glucopyranosyl)-3-C-formyl-beta-L-lyxopentanofuranoside; 2-[(1R,2R,3S,4R,5R,6S)-3-(diaminomethylideneamino)-4-[(2R,3R,4R,5S)-3-[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine; 2-[(1R,2R,3S,4R,5R,6S)-3-(diaminomethylideneamino)-4-[(2S,3S,4S,5R)-3-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine; 2-[(1S,2S,3R,4S,5S,6R)-3-(diaminomethylideneamino)-4-[(2R,3R,4R,5S)-3-[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine; 2-[(1S,4S)-5-(diaminomethylideneamino)-2-[(2R,5S)-3-[(2S,5R)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-3,4,6-trihydroxycyclohexyl]guanidine; [2-deoxy-2-(dimethylamino)-alpha-L-glucopyranosyl]-(1->2)-[5-deoxy-3-C-formyl-alpha-L-lyxofuranosyl]-(1->4)-{N',N'''-[(1,3,5/2,4,6)-2,4,5,6-tetrahydroxycyclohexane-1,3-diyl]diguanidine}

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 581.6
  Topological Polar Surface Area (xlogp); -8
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 12
  Hydrogen Bond Acceptor Count (hbondacc); 15
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.78 mL/min/kg [3]
  Elimination: 55% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 4.3 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 34.3888 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.65% [3]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.34 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 20 mg/mL [2]
• Chemical Identifiers:
  Formula: C21H39N7O12
  IUPAC Name: 2-[(1R,2R,3S,4R,5R,6S)-3-(diaminomethylideneamino)-4-[(2R,3R,4R,5S)-3-[(2S,3S,4S,5R,6S)-4,5-dihydroxy-6-(hydroxymethyl)-3-(methylamino)oxan-2-yl]oxy-4-formyl-4-hydroxy-5-methyloxolan-2-yl]oxy-2,5,6-trihydroxycyclohexyl]guanidine
  Canonical SMILES: C[C@H]1[C@@]([C@H]([C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H]([C@@H]([C@H]2O)O)N=C(N)N)O)N=C(N)N)O[C@H]3[C@H]([C@@H]([C@H]([C@@H](O3)CO)O)O)NC)(C=O)O
  InChI: InChI=1S/C21H39N7O12/c1-5-21(36,4-30)16(40-17-9(26-2)13(34)10(31)6(3-29)38-17)18(37-5)39-15-8(28-20(24)25)11(32)7(27-19(22)23)12(33)14(15)35/h4-18,26,29,31-36H,3H2,1-2H3,(H4,22,23,27)(H4,24,25,28)/t5-,6-,7+,8-,9-,10-,11+,12-,13-,14+,15+,16-,17-,18-,21+/m0/s1
  InChIKey: UCSJYZPVAKXKNQ-HZYVHMACSA-N
• Cross-matching ID:
  PubChem CID: 19649
  ChEBI ID: CHEBI:17076
  CAS Number: 57-92-1
  DrugBank ID: DB01082
  TTD ID: D0N0EQ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[5], [6]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Streptomycin

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cefotetan	DM07TX3	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefotetan.	Bacterial infection [1A00-1C4Z]	[16]
Kanamycin	DM2DMPO	Moderate	Increased risk of ototoxicity by the combination of Streptomycin and Kanamycin.	Bacterial infection [1A00-1C4Z]	[17]
Ceftizoxime	DM3VOGS	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Ceftizoxime.	Bacterial infection [1A00-1C4Z]	[16]
Cefoperazone	DM53PV8	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefoperazone.	Bacterial infection [1A00-1C4Z]	[16]
Cefprozil	DM7DSYP	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefprozil.	Bacterial infection [1A00-1C4Z]	[16]
Ceftriaxone	DMCEW64	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Ceftriaxone.	Bacterial infection [1A00-1C4Z]	[16]
Cefepime	DMHVWIK	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefepime.	Bacterial infection [1A00-1C4Z]	[16]
Cefpodoxime	DMJUNY5	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefpodoxime.	Bacterial infection [1A00-1C4Z]	[16]
Rabeprazole	DMMZXIW	Moderate	Increased risk of hypomagnesemia by the combination of Streptomycin and Rabeprazole.	Bacterial infection [1A00-1C4Z]	[18]
Cefazolin	DMPDYFR	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefazolin.	Bacterial infection [1A00-1C4Z]	[16]
Cefonicid	DMTX2BH	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefonicid.	Bacterial infection [1A00-1C4Z]	[16]
Cefradine	DMUNSWV	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefradine.	Bacterial infection [1A00-1C4Z]	[19]
Cefoxitin	DMYTXVR	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefoxitin.	Bacterial infection [1A00-1C4Z]	[16]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Streptomycin caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[17]
Cefuroxime	DMSIMD8	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefuroxime.	Acute bronchitis [CA42]	[16]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Streptomycin and Inotersen.	Amyloidosis [5D00]	[20]
Cefamandole	DMNEXZF	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cefamandole.	Anaerobic bacterial infection [1A00-1A09]	[16]
Iodipamide	DMXIQYS	Major	Increased risk of nephrotoxicity by the combination of Streptomycin and Iodipamide.	Cholelithiasis [DC11]	[21]
Atracurium	DM42HXN	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Atracurium.	Corneal disease [9A76-9A78]	[22]
Mivacurium	DM473VD	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Mivacurium.	Corneal disease [9A76-9A78]	[22]
Pancuronium	DMB0VY8	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Pancuronium.	Corneal disease [9A76-9A78]	[22]
Tubocurarine	DMBZIVP	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Tubocurarine.	Corneal disease [9A76-9A78]	[22]
Dexlansoprazole	DM1DBV5	Moderate	Increased risk of hypomagnesemia by the combination of Streptomycin and Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[18]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[17]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Streptomycin and Exjade.	Mineral absorption/transport disorder [5C64]	[23]
Neostigmine	DM6T2J3	Moderate	Additive neuromuscular blocking effects by the combination of Streptomycin and Neostigmine.	Myasthenia gravis [8C6Y]	[22]
Choline salicylate	DM8P137	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[24]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Streptomycin and Everolimus.	Renal cell carcinoma [2C90]	[25]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Streptomycin and Temsirolimus.	Renal cell carcinoma [2C90]	[25]
Salsalate	DM13P4C	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Salsalate.	Rheumatoid arthritis [FA20]	[24]
Cephapirin	DMV2JNY	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Cephapirin.	Sepsis [1G40-1G41]	[19]
Ifosfamide	DMCT3I8	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Ifosfamide.	Solid tumour/cancer [2A00-2F9Z]	[17]
Pipecuronium	DM5F84A	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Pipecuronium.	Tonus and reflex abnormality [MB47]	[22]
Doxacurium	DMKE7L9	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Doxacurium.	Tonus and reflex abnormality [MB47]	[22]
Vecuronium	DMP0UK2	Major	Additive neuromuscular blocking effects by the combination of Streptomycin and Vecuronium.	Tonus and reflex abnormality [MB47]	[22]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Streptomycin and Olsalazine.	Ulcerative colitis [DD71]	[26]
Plazomicin	DMKMBES	Moderate	Increased risk of ototoxicity by the combination of Streptomycin and Plazomicin.	Urinary tract infection [GC08]	[17]

References

• [1] Emerging drugs for chemotherapy-induced mucositis. Expert Opin Emerg Drugs. 2008 Sep;13(3):511-22.
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] 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
• [5] Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature. 2000 Sep 21;407(6802):340-8.
• [6] The interaction between streptomycin and ribosomal RNA. Biochimie. 1991 Dec;73(12):1431-8.
• [7] The glycylcyclines: a comparative review with the tetracyclines. Drugs. 2004;64(1):63-88.
• [8] Characterization of a 30S ribosomal subunit assembly intermediate found in Escherichia coli cells growing with neomycin or paromomycin. Arch Microbiol. 2008 May;189(5):441-9.
• [9] Ribosomal resistance in the gentamicin producer organism Micromonospora purpurea. Antimicrob Agents Chemother. 1982 Aug;22(2):231-6.
• [10] Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm. Front Biosci. 2000 Jan 1;5:D20-9.
• [11] Molecular dynamics simulations of the 30S ribosomal subunit reveal a preferred tetracycline binding site. J Am Chem Soc. 2008 Jan 30;130(4):1114-5.
• [12] Aminoglycoside association pathways with the 30S ribosomal subunit. J Phys Chem B. 2009 May 21;113(20):7322-30.
• [13] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [14] Reversed-phase high-performance liquid chromatography coupled to ultraviolet and electrospray time-of-flight mass spectrometry on-line detection fo... J Chromatogr A. 2008 Jun 27;1195(1-2):107-16.
• [15] Detection of tetracycline resistance genes by PCR methods. Methods Mol Biol. 2004;268:3-13.
• [16] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [17] Cerner Multum, Inc. "Australian Product Information.".
• [18] FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
• [19] Engle JE, Drago J, Carlin B, Schoolwerth AC "Letter: Reversible acute renal failure after cephalothin." Ann Intern Med 83 (1975): 232-3. [PMID: 1147461]
• [20] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [21] Wong GT, Lee EY, Irwin MG. Contrast induced nephropathy in vascular surgery.?Br J Anaesth. 2016;117 Suppl 2:ii63-ii73. [PMID: 27566809]
• [22] Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF "Mutual potentiation of the neuromuscular effects of antibiotics and relaxants." Anesth Analg 58 (1979): 107-15. [PMID: 571233]
• [23] Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
• [24] Assael BM, Chiabrando C, Gagliardi L, Noseda A, Bamonte F, Salmona M "Prostaglandins and aminoglycoside nephrotoxicity." Toxicol Appl Pharmacol 78 (1985): 386-94. [PMID: 4049389]
• [25] Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
• [26] Novis BH, Korzets Z, Chen P, Bernheim J "Nephrotic syndrome after treatment with 5-aminosalicylic acid." Br Med J (Clin Res Ed) 296 (1988): 1442. [PMID: 3132281]