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Identification
NameCycloserine
Accession NumberDB00260  (APRD00894, DB03123)
TypeSmall Molecule
GroupsApproved
DescriptionAntibiotic substance produced by Streptomyces garyphalus. [PubChem]
Structure
Thumb
Synonyms
(+)-4-Amino-3-isoxazolidinone
(+)-Cycloserine
(R)-4-AMINO-isoxazolidin-3-one
alpha-Cycloserine
Cicloserina
cyclo-D-Serine
Cycloserine
Cycloserinum
D-(+)-Cycloserine
D-4-amino-3-Isoxazolidinone
D-4-amino-3-Isoxazolidone
D-Cycloserine
DCS
Orientomycin
PA 94
PA-94
Ro-1-9213
Seromycin
α-Cycloserine
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Seromycin Cap 250mgCapsule250 mgOralEli Lilly Canada Inc1994-12-311997-08-13Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CycloserineCapsule250 mg/250mgOralPurdue GMP Center LLC dba The Chao Center2009-03-01Not applicableUs
CycloserineCapsule250 1/1OralPurdue GMP Center LLC1952-01-29Not applicableUs
SeromycinCapsule250 mg/250mgOralPurdue GMP Center LLC dba The Chao Center2009-03-01Not applicableUs
SeromycinCapsule250 mg/1OralREMEDYREPACK INC.2011-08-022016-10-13Us
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
OxamycinMerck
TisomycinLilly
Brand mixturesNot Available
SaltsNot Available
Categories
UNII95IK5KI84Z
CAS number68-41-7
WeightAverage: 102.0919
Monoisotopic: 102.042927446
Chemical FormulaC3H6N2O2
InChI KeyDYDCUQKUCUHJBH-UWTATZPHSA-N
InChI
InChI=1S/C3H6N2O2/c4-2-1-7-5-3(2)6/h2H,1,4H2,(H,5,6)/t2-/m1/s1
IUPAC Name
(4R)-4-amino-1,2-oxazolidin-3-one
SMILES
N[C@@H]1CONC1=O
Pharmacology
IndicationUsed in combination with up to 5 other drugs as a treatment for Mycobacterium avium complex (MAC) and is also used to treat tuberculosis (TB).
Structured Indications
PharmacodynamicsCycloserine, a broad-spectrum antibiotic, may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. Cycloserine works by blocking the formation of these peptidoglycans. By doing this the walls of the bacteria become weak and it results in the death of the bacteria
Mechanism of actionCycloserine is an analog of the amino acid D-alanine. It interferes with an early step in bacterial cell wall synthesis in the cytoplasm by competitive inhibition of two enzymes, L-alanine racemase, which forms D-alanine from L-alanine, and D-alanylalanine synthetase, which incorporates D-alanine into the pentapeptide necessary for peptidoglycan formation and bacterial cell wall synthesis.
TargetKindPharmacological actionActionsOrganismUniProt ID
D-alanine--D-alanine ligase AProteinyes
inhibitor
Escherichia coli (strain K12)P0A6J8 details
Alanine racemaseProteinyes
inhibitor
Mycobacterium aviumQ9L888 details
Related Articles
AbsorptionRapidly and almost completely absorbed (70 to 90%) from the gastrointestinal tract following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeHalf-life in patients with normal renal function is 10 hours, and is prolonged in patients with impaired renal function.
ClearanceNot Available
ToxicityOral LD50 in mouse is 5290 mg/kg, and in rat is over 5000 mg/kg. Symptoms of a cycloserine overdose include drowsiness, confusion, headache, dizziness, irritability, numbness and tingling, difficulty speaking, paralysis, abnormal behavior, seizures, and unconsciousness.
Affected organisms
  • Enteric bacteria and other eubacteria
  • Mycobacterium tuberculosis
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Cycloserine.Investigational
EthanolEthanol may increase the neurotoxic activities of Cycloserine.Approved
EthionamideThe risk or severity of adverse effects can be increased when Ethionamide is combined with Cycloserine.Approved
IsoniazidThe risk or severity of adverse effects can be increased when Isoniazid is combined with Cycloserine.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cycloserine.Approved
Food InteractionsNot Available
References
Synthesis Reference

Norman P. Jensen, “N-substituted cycloserine compounds, salts thereof, and processes for preparing them.” U.S. Patent US3932439, issued December, 1956.

US3932439
General ReferencesNot Available
External Links
ATC CodesJ04AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.4 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9909
Blood Brain Barrier+0.9382
Caco-2 permeable-0.6038
P-glycoprotein substrateNon-substrate0.7749
P-glycoprotein inhibitor INon-inhibitor0.9306
P-glycoprotein inhibitor IINon-inhibitor1.0
Renal organic cation transporterNon-inhibitor0.9522
CYP450 2C9 substrateNon-substrate0.9244
CYP450 2D6 substrateNon-substrate0.8168
CYP450 3A4 substrateNon-substrate0.5966
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9608
Ames testAMES toxic0.5756
CarcinogenicityNon-carcinogens0.8944
BiodegradationNot ready biodegradable0.7842
Rat acute toxicity1.3414 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9964
hERG inhibition (predictor II)Non-inhibitor0.9389
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Purdue gmp center llc dba the chao center industrial pharmacy
Packagers
Dosage forms
FormRouteStrength
CapsuleOral250 1/1
CapsuleOral250 mg/250mg
CapsuleOral250 mg/1
CapsuleOral250 mg
Prices
Unit descriptionCostUnit
Seromycin 250 mg capsule7.53USD each
Seromycin 250 mg pulvule6.0USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point155.5 dec °CPhysProp
water solubilitySolubleNot Available
logP-0.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility877.0 mg/mLALOGPS
logP-2.3ALOGPS
logP-2.4ChemAxon
logS0.93ALOGPS
pKa (Strongest Acidic)4.21ChemAxon
pKa (Strongest Basic)8.36ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area64.35 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity21.85 m3·mol-1ChemAxon
Polarizability8.87 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.89 KB)
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-0uy0-5900000000-06bce0b228f324fe49b4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
Substituents
  • Alpha-amino acid or derivatives
  • Oxazolidinone
  • Isoxazolidine
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Manganese ion binding
Specific Function:
Cell wall formation.
Gene Name:
ddlA
Uniprot ID:
P0A6J8
Molecular Weight:
39315.435 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Belanger AE, Porter JC, Hatfull GF: Genetic analysis of peptidoglycan biosynthesis in mycobacteria: characterization of a ddlA mutant of Mycobacterium smegmatis. J Bacteriol. 2000 Dec;182(23):6854-6. [PubMed:11073937 ]
  4. Noda M, Kawahara Y, Ichikawa A, Matoba Y, Matsuo H, Lee DG, Kumagai T, Sugiyama M: Self-protection mechanism in D-cycloserine-producing Streptomyces lavendulae. Gene cloning, characterization, and kinetics of its alanine racemase and D-alanyl-D-alanine ligase, which are target enzymes of D-cycloserine. J Biol Chem. 2004 Oct 29;279(44):46143-52. Epub 2004 Aug 9. [PubMed:15302885 ]
  5. McCoy AJ, Maurelli AT: Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D-alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine sensitivity. Mol Microbiol. 2005 Jul;57(1):41-52. [PubMed:15948948 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Mycobacterium avium
Pharmacological action
yes
Actions
inhibitor
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the interconversion of L-alanine and D-alanine.
Gene Name:
alr
Uniprot ID:
Q9L888
Molecular Weight:
41001.515 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Feng Z, Barletta RG: Roles of Mycobacterium smegmatis D-alanine:D-alanine ligase and D-alanine racemase in the mechanisms of action of and resistance to the peptidoglycan inhibitor D-cycloserine. Antimicrob Agents Chemother. 2003 Jan;47(1):283-91. [PubMed:12499203 ]
  4. Fenn TD, Stamper GF, Morollo AA, Ringe D: A side reaction of alanine racemase: transamination of cycloserine. Biochemistry. 2003 May 20;42(19):5775-83. [PubMed:12741835 ]
  5. Fenn TD, Holyoak T, Stamper GF, Ringe D: Effect of a Y265F mutant on the transamination-based cycloserine inactivation of alanine racemase. Biochemistry. 2005 Apr 12;44(14):5317-27. [PubMed:15807525 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Gene Name:
DDC
Uniprot ID:
P20711
Molecular Weight:
53925.815 Da
References
  1. DENGLER HJ, RAUCHS E, RUMMEL W: [On the inhibition of L-glutamic acid and L-DOPA decarboxylase by D-cycloserine and other isoxazolidones]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1962;243:366-81. [PubMed:13885421 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
L-proline transmembrane transporter activity
Specific Function:
Involved in a pH-dependent electrogenic neuronal transport and sequestration of small amino acids. Transports glycine and proline. Inhibited by sarcosine (By similarity).
Gene Name:
SLC36A2
Uniprot ID:
Q495M3
Molecular Weight:
53215.65 Da
References
  1. Kennedy DJ, Gatfield KM, Winpenny JP, Ganapathy V, Thwaites DT: Substrate specificity and functional characterisation of the H+/amino acid transporter rat PAT2 (Slc36a2). Br J Pharmacol. 2005 Jan;144(1):28-41. [PubMed:15644866 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23