telotristat ethyl 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
enzyme inhibitors 5214 1033805-22-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • telotristat ethyl
  • xermelo
  • telotristat etiprate
  • LX1606
  • LX 1606
Telotristat, the active metabolite of telotristat ethyl, is an inhibitor of tryptophan hydroxylase, which mediates the rate limiting step in serotonin biosynthesis. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase is 29 times higher than that of telotristat ethyl. Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the gastrointestinal tract, and is over-produced in patients with carcinoid syndrome. Through inhibition of tryptophan hydroxylase, telotristat and telotristat ethyl reduce the production of peripheral serotonin, and the frequency of carcinoid syndrome diarrhea.
  • Molecular weight: 574.99
  • Formula: C27H26ClF3N6O3
  • CLOGP: 6.03
  • LIPINSKI: 2
  • HAC: 9
  • HDO: 2
  • TPSA: 131.17
  • ALOGS: -5.29
  • ROTB: 11
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,CDK9,ERBB2,GRK2,ITK,MAPK10,MET,PDK1,PDK2,PDK4,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC 18
kinase-selectivity-class AXL,PDK1 2
pfas-class PFAS structural alert (1 = True, 0 = False) 1

Approvals:

DateAgencyCompanyOrphan
Sept. 18, 2017 EMA Ipsen Pharma
Feb. 28, 2017 FDA LEXICON PHARMA INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Constipation 57.58 37.28 38 1064 280357 90346988
Abdominal pain 50.10 37.28 40 1062 395681 90231664
Flushing 48.73 37.28 23 1079 88468 90538877
Flatulence 39.97 37.28 16 1086 41351 90585994
Disease progression 38.94 37.28 24 1078 156591 90470754
Death 37.28 37.28 36 1066 456515 90170830

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Flushing 85.79 40.18 34 1173 36994 42583134
Abdominal pain 72.14 40.18 52 1155 190419 42429709
Diarrhoea 63.74 40.18 71 1136 460778 42159350
Constipation 49.49 40.18 39 1168 162252 42457876
Serum serotonin increased 46.80 40.18 7 1200 107 42620021
Blood chromogranin A increased 46.10 40.18 8 1199 320 42619808

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Flushing 67.39 36.01 30 1268 104706 110483295
Abdominal pain 48.09 36.01 43 1255 512946 110075055
Death 47.44 36.01 49 1249 698820 109889181
Disease progression 43.62 36.01 30 1268 244004 110343997
Hospice care 41.08 36.01 12 1286 12461 110575540
Diarrhoea 39.76 36.01 57 1241 1139448 109448553
Flatulence 36.92 36.01 16 1282 52133 110535868
Nausea 36.23 36.01 57 1241 1235633 109352368

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35610 antineoplastic agent

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Diarrhea indication 62315008




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.14 Basic
pKa2 2.78 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 250MG BASE XERMELO TERSERA N208794 Feb. 28, 2017 RX TABLET ORAL 7968559 Dec. 11, 2027 THE TREATMENT OF CARCINOID SYNDROME DIARRHEA IN COMBINATION WITH SOMATOSTATIN ANALOG (SSA) THERAPY IN ADULTS INADEQUATELY CONTROLLED BY SSA THERAPY
EQ 250MG BASE XERMELO TERSERA N208794 Feb. 28, 2017 RX TABLET ORAL 8653094 Dec. 19, 2028 THE TREATMENT OF CARCINOID SYNDROME DIARRHEA IN COMBINATION WITH SOMATOSTATIN ANALOG (SSA) THERAPY IN ADULTS INADEQUATELY CONTROLLED BY SSA THERAPY
EQ 250MG BASE XERMELO TERSERA N208794 Feb. 28, 2017 RX TABLET ORAL 7709493 Feb. 28, 2031 THE TREATMENT OF CARCINOID SYNDROME DIARRHEA IN COMBINATION WITH SOMATOSTATIN ANALOG (SSA) THERAPY IN ADULTS INADEQUATELY CONTROLLED BY SSA THERAPY

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Tryptophan 5-hydroxylase 1 Enzyme INHIBITOR IC50 7.80 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
8G388563M7 UNII
1137608-69-5 SECONDARY_CAS_RN
4036470 VANDF
C4317559 UMLSCUI
CHEBI:751580 CHEBI
CHEMBL2105695 ChEMBL_ID
25181577 PUBCHEM_CID
DB12095 DRUGBANK_ID
D09974 KEGG_DRUG
CHEMBL3348963 ChEMBL_ID
C000621725 MESH_SUPPLEMENTAL_RECORD_UI
9490 IUPHAR_LIGAND_ID
C000592493 MESH_SUPPLEMENTAL_RECORD_UI
41129611000001104 SNOMEDCT_US
733879005 SNOMEDCT_US
252423 MMSL
32389 MMSL
d08528 MMSL
017120 NDDF
017121 NDDF
1872441 RXNORM

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Xermelo HUMAN PRESCRIPTION DRUG LABEL 1 70183-125 TABLET 250 mg ORAL NDA 24 sections
Xermelo HUMAN PRESCRIPTION DRUG LABEL 1 70183-125 TABLET 250 mg ORAL NDA 24 sections
Xermelo HUMAN PRESCRIPTION DRUG LABEL 1 70720-125 TABLET 250 mg ORAL NDA 25 sections