Disopyramide

drug
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Also known as (rs)-disopyramideDicorantilDisopiramidaDl-disopyramideH-3292IsorythmLispineRitmilenRythmodan pSC-7031Searle-703SID50106174SID85231006SID90340571SID90341382SID85148360SID174006632SID144204278SID170464947

Summary

Disopyramide (CHEMBL517) is an approved small-molecule anti-arrhythmia drug (ATC C01BA03) targeting KCNH2; indicated across 3 conditions including atrial fibrillation and heart failure.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: C01BA03
  • Targets: 1 (KCNH2)
  • Indications: 3 conditions
  • Clinical trials: 2
  • Chemistry: 339.5 Da · C21H29N3O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL517
NameDisopyramide
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID3114
ChEBICHEBI:4657
ATCC01BA03
Molecular formulaC21H29N3O
Molecular weight339.5
InChIKeyUVTNFZQICZKOEM-UHFFFAOYSA-N

SMILES: CC(C)N(CCC(C1=CC=CC=C1)(C2=CC=CC=N2)C(=O)N)C(C)C

IUPAC name: 4-[di(propan-2-yl)amino]-2-phenyl-2-pyridin-2-ylbutanamide

ChEBI definition: A monocarboxylic acid amide that is butanamide substituted by a diisopropylamino group at position 4, a phenyl group at position 2 and a pyridin-2-yl group at position 2. It is used as a anti-arrhythmia drug.

Pharmacological roles (ChEBI): anti-arrhythmia drug.

Also known as: (rs)-disopyramide, Dicorantil, Disopiramida, Disopyramide, Dl-disopyramide, H-3292, Isorythm, Lispine, Ritmilen, Rythmodan p, SC-7031, Searle-703

Parent form; salt/anhydrous children: CHEMBL1201020

Patent coverage: 3,172 distinct patent families (11,140 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 11,139 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
KCNH2Kv11.1Inhibition4.040.3%Q12809

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: RecQ-like DNA helicase BLM, Peripheral myelin protein 22, Solute carrier family 22 member 2, Multidrug and toxin extrusion protein 1, Solute carrier family 22 member 2, Thyroid hormone receptor beta, Solute carrier family 22 member 1, Progesterone receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2.

Bioactivity

ChEMBL activities: 7 potent at pChembl ≥ 5 of 21 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
BLM6.25Potency562.3nMCHEMBL_ACT_4749910
BLM6.25Potency562.3nMCHEMBL_ACT_4933856
SLC22A25.54IC502900nMCHEMBL_ACT_12064059
THRB5.5Potency3162nMCHEMBL_ACT_4020966
PDE3A5.27AC505400nMCHEMBL_ACT_25190873
OPRK15.17AC506731nMCHEMBL_ACT_25129593
ADRB35.08AC508370nMCHEMBL_ACT_25153353

Target pathways

Aggregated over 1 target gene(s): KCNH2.

Top Reactome pathways

6 total, by targets touching each:

PathwayTargetsGenes
Neuronal System1KCNH2
Potassium Channels1KCNH2
Voltage gated Potassium channels1KCNH2
Muscle contraction1KCNH2
Phase 3 - rapid repolarisation1KCNH2
Cardiac conduction1KCNH2

Dominant GO biological processes

GO termTargets
regulation of heart rate by hormone1
potassium ion transport1
regulation of membrane potential1
positive regulation of DNA-templated transcription1
potassium ion homeostasis1
cardiac muscle contraction1
regulation of membrane repolarization1
regulation of ventricular cardiac muscle cell membrane repolarization1
cellular response to xenobiotic stimulus1
potassium ion transmembrane transport1
ventricular cardiac muscle cell action potential1
membrane repolarization1
membrane depolarization during action potential1
membrane repolarization during action potential1
membrane repolarization during cardiac muscle cell action potential1

Indications & clinical

Indications

3 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
atrial fibrillation3MONDO:0004981EFO:0000275
heart failure3MONDO:0005252EFO:0003144

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 2.

Phase distribution

PhaseTrials
PHASE31
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00000556PHASE3COMPLETEDAtrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
NCT02294955Not specifiedUNKNOWNCatheter Ablation Compared With Pharmacological Therapy for Atrial Fibrillation (CAPTAF Trial)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

GuidelineSourceGene(s)DosingRecommendation
Annotation of DPWG Guideline for disopyramide and CYP2D6DPWGCYP2D6

PharmGKB also curates 1 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

617 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
AFATINIBChEMBL + PubChemPhase 4 (approved)KCNH2
DIHYDROERGOTAMINEChEMBL + PubChemPhase 4 (approved)KCNH2
GENTIAN VIOLETChEMBL + PubChemPhase 4 (approved)KCNH2
MAVORIXAFORChEMBL + PubChemPhase 4 (approved)KCNH2
PIMAVANSERINChEMBL + PubChemPhase 4 (approved)KCNH2
PROPOXYPHENEChEMBL + PubChemPhase 4 (approved)KCNH2
RELUGOLIXChEMBL + PubChemPhase 4 (approved)KCNH2
RIOCIGUATChEMBL + PubChemPhase 4 (approved)KCNH2
VORAPAXARChEMBL + PubChemPhase 4 (approved)KCNH2
ABEMACICLIBChEMBLPhase 4 (approved)KCNH2
ACENOCOUMAROLChEMBLPhase 4 (approved)KCNH2
ACETOPHENAZINEChEMBLPhase 4 (approved)KCNH2
ACLIDINIUM BROMIDEChEMBLPhase 4 (approved)KCNH2
ALBENDAZOLEChEMBLPhase 4 (approved)KCNH2
ALMOTRIPTANChEMBLPhase 4 (approved)KCNH2
ALOSETRONChEMBLPhase 4 (approved)KCNH2
ALPIDEMChEMBLPhase 4 (approved)KCNH2
AMBENONIUMChEMBLPhase 4 (approved)KCNH2
AMCINONIDEChEMBLPhase 4 (approved)KCNH2
AMIODARONEChEMBLPhase 4 (approved)KCNH2
AMISULPRIDEChEMBLPhase 4 (approved)KCNH2
AMITRIPTYLINEChEMBLPhase 4 (approved)KCNH2
AMLODIPINEChEMBLPhase 4 (approved)KCNH2
AMODIAQUINEChEMBLPhase 4 (approved)KCNH2
AMOROLFINEChEMBLPhase 4 (approved)KCNH2
AMOXAPINEChEMBLPhase 4 (approved)KCNH2
AMSACRINEChEMBLPhase 4 (approved)KCNH2
ANISOTROPINEChEMBLPhase 4 (approved)KCNH2
ANTAZOLINEChEMBLPhase 4 (approved)KCNH2
APOMORPHINEChEMBLPhase 4 (approved)KCNH2
ARIPIPRAZOLEChEMBLPhase 4 (approved)KCNH2
ASCIMINIBChEMBLPhase 4 (approved)KCNH2
ASENAPINEChEMBLPhase 4 (approved)KCNH2
ASTEMIZOLEChEMBLPhase 4 (approved)KCNH2
ATOMOXETINEChEMBLPhase 4 (approved)KCNH2
ATRACURIUMChEMBLPhase 4 (approved)KCNH2
AVATROMBOPAGChEMBLPhase 4 (approved)KCNH2
AZELASTINEChEMBLPhase 4 (approved)KCNH2
BAZEDOXIFENEChEMBLPhase 4 (approved)KCNH2
BEDAQUILINEChEMBLPhase 4 (approved)KCNH2
BENFLUOREXChEMBLPhase 4 (approved)KCNH2
BENOXINATEChEMBLPhase 4 (approved)KCNH2
BENPERIDOLChEMBLPhase 4 (approved)KCNH2
BENZPHETAMINEChEMBLPhase 4 (approved)KCNH2
BENZTROPINEChEMBLPhase 4 (approved)KCNH2
BENZYDAMINEChEMBLPhase 4 (approved)KCNH2
BEPRIDILChEMBLPhase 4 (approved)KCNH2
BERBERINEChEMBLPhase 4 (approved)KCNH2
BETRIXABANChEMBLPhase 4 (approved)KCNH2
BEXAROTENEChEMBLPhase 4 (approved)KCNH2
BIFONAZOLEChEMBLPhase 4 (approved)KCNH2
BIPERIDENChEMBLPhase 4 (approved)KCNH2
BITHIONOLChEMBLPhase 4 (approved)KCNH2
BOSUTINIBChEMBLPhase 4 (approved)KCNH2
BROMHEXINEChEMBLPhase 4 (approved)KCNH2
BROMPERIDOLChEMBLPhase 4 (approved)KCNH2
BUCLIZINEChEMBLPhase 4 (approved)KCNH2
BUFLOMEDILChEMBLPhase 4 (approved)KCNH2
BUPIVACAINEChEMBLPhase 4 (approved)KCNH2
BUPRENORPHINEChEMBLPhase 4 (approved)KCNH2