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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 IDs Not Available
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Seromycin Cap 250mgCapsule250 mgOralEli Lilly & Co. Ltd.1994-12-311997-08-13Canada
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/1OralRemedy Repack2011-08-022016-10-13Us
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
OxamycinMerck
TisomycinLilly
Brand mixturesNot 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
Pharmacogenomic Effects/ADRs Not 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)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0Enrolling by InvitationTreatmentBipolar Disorder (BD) / Schizophrenia1
0RecruitingBasic ScienceChronic Obstructive Pulmonary Disease (COPD)1
0RecruitingTreatmentBody Dysmorphic Disorders1
0RecruitingTreatmentNicotine Addiction / Panic Attacks1
0RecruitingTreatmentOsteomyelitis1
0RecruitingTreatmentSocial Anxiety Disorder (SAD)1
0Unknown StatusTreatmentTraumatic Brain Injury (TBI)1
1CompletedNot AvailableDrug Dependence1
1CompletedNot AvailableNicotine Addiction1
1CompletedBasic ScienceSchizophrenia1
1CompletedTreatmentAnaplastic Astrocytoma (AA) / Ependymomas / Glioblastomas / Medulloblastomas / Tumor, Brain1
1CompletedTreatmentHealthy Volunteers1
1RecruitingTreatmentAnxiety Disorder1
1TerminatedTreatmentLeukemias1
1TerminatedTreatmentSleep Apnea Syndromes1
1, 2CompletedTreatmentFeeding Disorders / Specific Phobias1
2CompletedNot AvailableCocaine Use Disorders1
2CompletedTreatmentAnxiety / Phobic Disorders / Social Phobia1
2CompletedTreatmentBipolar Disorder (BD) / Major Depressive Disorder (MDD)1
2CompletedTreatmentCocaine Use Disorders1
2CompletedTreatmentCocaine-Related Disorders1
2CompletedTreatmentFear of open spaces1
2CompletedTreatmentGastric Cancers1
2CompletedTreatmentLow Back Pain (LBP) / Pain1
2CompletedTreatmentMajor Depressive Disorder (MDD)1
2CompletedTreatmentObsessive-Compulsive Disorder (OCD)1
2CompletedTreatmentPhobic Disorders1
2CompletedTreatmentPlacebo / Treatments1
2CompletedTreatmentStroke2
2CompletedTreatmentSubstance-Related Disorders1
2Not Yet RecruitingTreatmentSocial Anxiety Disorder (SAD)1
2RecruitingTreatmentAstrocytoma, Grade IV / Giant Cell Glioblastoma / Glioblastoma Multiforme / Glioblastomas1
2RecruitingTreatmentGulf War Illness1
2RecruitingTreatmentMajor Depressive Disorder (MDD)1
2Unknown StatusNot AvailableSmoking, Cigarette1
2Unknown StatusTreatmentObsessive-Compulsive Disorder (OCD)1
2Unknown StatusTreatmentPosttraumatic Stress Disorders / PTSD2
2Unknown StatusTreatmentPanic Disorders1
2Unknown StatusTreatmentTraumatic Brain Injury (TBI)1
2WithdrawnNot AvailableObsessive Compulsive Disorder (OCD)1
2WithdrawnTreatmentOpioid-Related Disorders1
2WithdrawnTreatmentSmokers1
2, 3CompletedTreatmentSchizoaffective Disorders / Schizophrenia1
2, 3CompletedTreatmentStress Disorders, Post Traumatic1
2, 3Unknown StatusBasic ScienceAlcohol Drinking1
2, 3Unknown StatusTreatmentPost-Traumatic Stress Disorder (PTSD)1
3Active Not RecruitingTreatmentObsessive-Compulsive Disorder (OCD)1
3CompletedTreatmentAsperger's Disorder / Autistic Disorder / Pervasive Developmental Disorder NOS1
3CompletedTreatmentAutistic Disorder2
3CompletedTreatmentCessation, Smoking1
3CompletedTreatmentObsessive-Compulsive Disorder (OCD)1
3CompletedTreatmentPhobic Disorders1
3CompletedTreatmentSchizophrenia1
3CompletedTreatmentSocial Anxiety Disorder (SAD)1
3RecruitingBasic SciencePanic Disorders1
3TerminatedSupportive CareCancer, Breast / Neurotoxicity / Pain1
3WithdrawnTreatmentSchizophrenia1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentChronic Prostatitis With Chronic Pelvic Pain Syndrome1
4CompletedTreatmentObsessive-Compulsive Disorder (OCD)1
4CompletedTreatmentPost-Traumatic Stress Disorder (PTSD)1
4CompletedTreatmentSchizophrenia2
4CompletedTreatmentSocial Anxiety Disorder (SAD)1
4Not Yet RecruitingTreatmentSpinal Cord Injuries (SCI)1
4Not Yet RecruitingTreatmentTreatment Resistant Depression (TRD)1
4RecruitingTreatmentDelusional Disorder / Schizoaffective Disorders / Schizophrenia1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4RecruitingTreatmentObsessive-Compulsive Disorder (OCD)1
4RecruitingTreatmentSpinal Cord Injuries (SCI)1
4WithdrawnTreatmentSchizophrenia1
Not AvailableActive Not RecruitingBasic ScienceStress Disorders, Posttraumatic1
Not AvailableCompletedPreventionAlcohol Dependence / Alcohol Dependent1
Not AvailableCompletedTreatmentAnorexia and Bulimia Nervosa1
Not AvailableCompletedTreatmentCocaine Addictions1
Not AvailableCompletedTreatmentCombat Disorders / Stress Disorders, Post-Traumatic1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
Not AvailableCompletedTreatmentObsessive Compulsive Disorder (OCD)1
Not AvailableCompletedTreatmentObsessive-Compulsive Disorder (OCD)2
Not AvailableCompletedTreatmentPanic Disorders1
Not AvailableCompletedTreatmentPosttraumatic Stress Disorders1
Not AvailableCompletedTreatmentSchizophrenia1
Not AvailableCompletedTreatmentSmoking1
Not AvailableCompletedTreatmentSpecific Phobias1
Not AvailableRecruitingBasic ScienceMajor Depressive Disorder (MDD)1
Not AvailableRecruitingTreatmentChronic Tic Disorders / Tourette's Disorder1
Not AvailableRecruitingTreatmentPain, Chronic / Post Treatment Lyme Syndrome (PTLS)1
Not AvailableRecruitingTreatmentPosttraumatic Stress Disorders1
Not AvailableUnknown StatusNot Available3 Conditions Including 250 mg Syromycin, 500 mg Seromycin, and Placebo1
Not AvailableUnknown StatusBasic ScienceHealthy Individuals1
Not AvailableUnknown StatusTreatmentHeight Phobia1
Not AvailableWithdrawnTreatmentPsychological Trauma1
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
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 )
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 chemical entities known as isoxazolines. These are compounds containing a five-member unsaturated aliphatic ring, with an oxygen atom adjacent to a nitrogen atoms, and three carbon atoms.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassAzolines
Direct ParentIsoxazolines
Alternative Parents
Substituents
  • Isoxazoline
  • Oxacycle
  • Azacycle
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • 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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23