Cycloserine

Identification

Summary

Cycloserine is a broad-spectrum antibiotic used in the treatment of tuberculosis and certain urinary tract infections (UTI).

Brand Names
Seromycin
Generic Name
Cycloserine
DrugBank Accession Number
DB00260
Background

Antibiotic substance produced by Streptomyces garyphalus.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 102.0919
Monoisotopic: 102.042927446
Chemical Formula
C3H6N2O2
Synonyms
  • (+)-4-amino-3-isoxazolidinone
  • (+)-cycloserine
  • alpha-Cycloserine
  • Cicloserina
  • cyclo-D-Serine
  • Cycloserine
  • Cyclosérine
  • Cycloserinum
  • D-(+)-cycloserine
  • D-4-amino-3-isoxazolidinone
  • D-4-amino-3-isoxazolidone
  • D-Cycloserine
  • DCS
  • Orientomycin
  • α-Cycloserine
External IDs
  • NSC-154851
  • NSC-76029
  • PA 94
  • PA-94
  • Ro-1-9213

Pharmacology

Indication

Used in combination with up to 5 other drugs as a treatment for Mycobacterium avium complex (MAC) and is also used to treat tuberculosis (TB).

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Cycloserine, 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 action

Cycloserine 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.

TargetActionsOrganism
AD-alanine--D-alanine ligase A
inhibitor
Escherichia coli (strain K12)
AAlanine racemase
inhibitor
Mycobacterium avium
Absorption

Rapidly and almost completely absorbed (70 to 90%) from the gastrointestinal tract following oral administration.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Half-life in patients with normal renal function is 10 hours, and is prolonged in patients with impaired renal function.

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Oral 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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolThe risk or severity of bleeding can be increased when Cycloserine is combined with Acenocoumarol.
AcetophenazineCycloserine may increase the neurotoxic activities of Acetophenazine.
AlimemazineCycloserine may increase the neurotoxic activities of Alimemazine.
AmisulprideCycloserine may increase the neurotoxic activities of Amisulpride.
AmitriptylineCycloserine may increase the neurotoxic activities of Amitriptyline.
AmitriptylinoxideCycloserine may increase the neurotoxic activities of Amitriptylinoxide.
AmoxapineCycloserine may increase the neurotoxic activities of Amoxapine.
AripiprazoleCycloserine may increase the neurotoxic activities of Aripiprazole.
Aripiprazole lauroxilCycloserine may increase the neurotoxic activities of Aripiprazole lauroxil.
AsenapineCycloserine may increase the neurotoxic activities of Asenapine.
Interactions
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Food Interactions
  • Do not take with or immediately after a high-fat meal. High-fat meals may reduce the rate of absorption; however, the impact on the extent of absorption is unknown.

Products

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International/Other Brands
Oxamycin (Merck) / Tisomycin (Lilly)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CycloserineCapsule250 mg/1OralMacleods Pharmaceuticals Limited2019-01-18Not applicableUS flag
SeromycinCapsule250 mg/1OralEli Lilly & Co. Ltd.1956-09-012010-02-08US flag
Seromycin Cap 250mgCapsule250 mg / capOralEli Lilly & Co. Ltd.1994-12-311997-08-13Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CycloserineCapsule250 mg/250mgOralParsolex Gmp Center, Inc.2009-03-01Not applicableUS flag
CycloserineCapsule250 1/1OralParsolex Gmp Center, Inc.1952-01-29Not applicableUS flag
SeromycinCapsule250 mg/1OralParsolex Gmp Center, Inc.2009-03-01Not applicableUS flag
SeromycinCapsule250 mg/1OralRemedy Repack2011-08-022011-08-02US flag
SeromycinCapsule250 mg/250mgOralParsolex Gmp Center, Inc.2009-03-01Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
CycloserineCycloserine (250 mg/1)CapsuleOralMacleods Pharmaceuticals Limited2019-01-18Not applicableUS flag

Categories

ATC Codes
J04AB01 — Cycloserine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azolines
Sub Class
Isoxazolines
Direct Parent
Isoxazolines
Alternative Parents
Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
Aliphatic heteromonocyclic compound / Amine / Azacycle / Hydrocarbon derivative / Isoxazoline / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
organooxygen heterocyclic antibiotic, organonitrogen heterocyclic antibiotic, 4-amino-1,2-oxazolidin-3-one (CHEBI:40009) / Non-ribosomal peptide/polyketide hybrids (C08057) / Non-ribosomal peptide/polyketide hybrids (LMPK14000007)
Affected organisms
  • Enteric bacteria and other eubacteria
  • Mycobacterium tuberculosis

Chemical Identifiers

UNII
95IK5KI84Z
CAS number
68-41-7
InChI Key
DYDCUQKUCUHJBH-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

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 References
Not Available
Human Metabolome Database
HMDB0014405
KEGG Compound
C08057
PubChem Compound
6234
PubChem Substance
46506865
ChemSpider
5998
BindingDB
50103516
RxNav
3007
ChEBI
40009
ChEMBL
CHEMBL771
ZINC
ZINC000034676245
Therapeutic Targets Database
DAP001468
PharmGKB
PA164764600
PDBe Ligand
4AX
Drugs.com
Drugs.com Drug Page
Wikipedia
Cycloserine
PDB Entries
1pb9 / 1xql
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic SciencePost Traumatic Stress Disorder (PTSD)1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentChronic Prostatitis With Chronic Pelvic Pain Syndrome1
4CompletedTreatmentDelusional Disorder / Schizoaffective Disorders / Schizophrenia1
4CompletedTreatmentObsessive Compulsive Disorder (OCD)2
4CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
4CompletedTreatmentSchizophrenia2
4CompletedTreatmentSocial Anxiety Disorder (SAD)1
4CompletedTreatmentSpinal Cord Injuries (SCI)1
4Unknown StatusTreatmentMajor depressive disorder, recurrent episode1

Pharmacoeconomics

Manufacturers
  • Purdue gmp center llc dba the chao center industrial pharmacy
Packagers
  • Eli Lilly & Co.
  • Purdue Pharma LP
  • The Chao Center
Dosage Forms
FormRouteStrength
Capsule, coatedOral250 mg
CapsuleOral
CapsuleOral250 1/1
CapsuleOral250 mg
CapsuleOral250 mg/1
CapsuleOral250 mg/250mg
CapsuleOral250 mg / cap
Tablet250 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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155.5 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-0uy0-5900000000-06bce0b228f324fe49b4
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-MSGC-MSsplash10-0uy0-5900000000-06bce0b228f324fe49b4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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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
Uniprot Name
D-alanine--D-alanine ligase A
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
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
Uniprot Name
Alanine racemase
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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
Uniprot Name
Aromatic-L-amino-acid decarboxylase
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. [Article]

Transporters

Kind
Protein
Organism
Humans
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
Uniprot Name
Proton-coupled amino acid transporter 2
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. [Article]

Drug created on June 13, 2005 13:24 / Updated on August 07, 2021 00:19