Drug Information

Drug (ID: DG00922) and It's Reported Resistant Information

• Name: Cabergoline
• Synonyms: Cabergoline; 81409-90-7; Dostinex; Cabaser; Cabergolinum [Latin]; Cabergolina [Spanish]; Cabergolinum; Cabergolina; FCE-21336; FCE 21336; UNII-LL60K9J05T; C26H37N5O2; 1-((6-Allylergolin-8beta-yl)carbonyl)-1-(3-(dimethylamino)propyl)-3-ethylurea; Cabaseril; CHEBI:3286; LL60K9J05T; MFCD00867887; DSSTox_CID_2719; 1-[(6-allylergoline-8beta-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethylurea; 1-ethyl-3-(3'-dimethylamionpropyl)-2-(6'-allylergoline-8'beta-carbonyl)urea; (8R)-6-allyl-N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)ergoline-8-carboxamide; DSSTox_RID_76698; DSSTox_GSID_22719; (6aR,9R,10aR)-7-allyl-N-(3-(dimethylamino)propyl)-N-(ethylcarbamoyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide; (8beta)-N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)-ergoline-8-carboxamide; Sogilen; Dostinex (TN); 1-[3-(dimethylamino)propyl]-3-ethyl-1-{[(2R,4R,7R)-6-(prop-2-en-1-yl)-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),9,12,14-tetraen-4-yl]carbonyl}urea; Cabaser (TN); CAS-81409-90-7; SR-05000001493; BRN 6020775; Caberlin; Velactis; NCGC00167821-01; Cabergoline [USAN:USP:INN:BAN]; CG-101; GTPL37; SCHEMBL42292; (8beta)-N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)-6-(prop-2-en-1-yl)ergoline-8-carboxamide; BIDD:GT0775; Cabergoline (JAN/USP/INN); CHEMBL1201087; DTXSID6022719; Cabergoline, >=98% (HPLC); HMS2090A09; HMS3886H05; ZINC3800008; Tox21_112589; BDBM50426497; s5842; 1-Ethyl-3-(3'-dimethylaminopropyl)-3-(6'-allylergoline-8'beta-carbonyl)urea; AKOS015961587; Tox21_112589_1; DB00248; FCE-21336FCE-21336; NCGC00344544-01; (8beta)-N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonyl]-6-prop-2-en-1-ylergoline-8-carboxamide; AC-26126; Ergoline-8-carboxamide, N-(3-(dimethylamino)propyl)-N-((ethylamino)carbonyl)-6-(2-propenyl)-, (8-beta)-; Ergoline-8beta-carboxamide, N-(3-(dimethylamino)propyl)-N-((ethylamino)carbonyl)-6-(2-propenyl)-; HY-15296; K450; C08187; D00987; F17353; AB01275484-01; 409C907; Q423308; SR-05000001493-1; SR-05000001493-2; BRD-K86882815-001-01-6; Cabergoline, European Pharmacopoeia (EP) Reference Standard; Cabergoline, United States Pharmacopeia (USP) Reference Standard; ETHYL4-METHYL-2-PYRIDIN-3-YL-1,3-THIAZOLE-5-CARBOXYLATE; 1-[(6-Allylergoline-8beta-yl)carbonyl]-1-[3-(dimethylamino)-propyl]-3-ethylurea; 6-allyl-N-[3-(dimethylamino)propyl]-N-[(ethylamino)carbonyl]-ergoline-8beta-carboxamide; N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)-6-allyl-ergoline-8beta-carboxamide; (6aR,9R,10aR)-N-[3-(dimethylamino)propyl]-N-(ethylcarbamoyl)-7-prop-2-enyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide; (9R,10aR)-7-allyl-N-(3-(dimethylamino)propyl)-N-(ethylcarbamoyl)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxamide
• Indication:
  In total 1 Indication(s)
  Hyperprolactinaemia [ICD-11: 5A60-5A61]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Pituitary cancer [ICD-11: 2F37]; [2]
• Target: Dopamine D2 receptor (D2R); DRD2_HUMAN; [2]
• Formula: C26H37N5O2
• IsoSMILES: CCNC(=O)N(CCCN(C)C)C(=O)[C@@H]1C[C@H]2[C@@H](CC3=CNC4=CC=CC2=C34)N(C1)CC=C
• InChI: 1S/C26H37N5O2/c1-5-11-30-17-19(25(32)31(26(33)27-6-2)13-8-12-29(3)4)14-21-20-9-7-10-22-24(20)18(16-28-22)15-23(21)30/h5,7,9-10,16,19,21,23,28H,1,6,8,11-15,17H2,2-4H3,(H,27,33)/t19-,21-,23-/m1/s1
• InChIKey: KORNTPPJEAJQIU-KJXAQDMKSA-N
• PubChem CID: 54746
• ChEBI ID: CHEBI:3286
• TTD Drug ID: D04EGX
• VARIDT ID: DR00069
• INTEDE ID: DR0253
• DrugBank ID: DB00248

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Pituitary cancer [ICD-11: 2F37]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Dopamine receptor D2 (DRD2) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Generally, the effectiveness of BRC or CAB has been related to a decreased expression in DRs, as the expression of such receptors has been shown to correlate with responsiveness to therapy in lactotroph, somatotroph, corticotroph and in clinically nonfunctioning PitNET.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-17-5p [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.

Key Molecule: hsa-mir-93 [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Knockdown of mir-93 increased the sensitivity of MMQ cells to bromocriptine treatment, and these effects were abolished when p21 was knocked-down using siRNA.

References

• Ref 1: Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms .Front Endocrinol (Lausanne). 2022 Jan 12;12:791633. doi: 10.3389/fendo.2021.791633. eCollection 2021. 10.3389/fendo.2021.791633
• Ref 2: MicroRNA expression profile of bromocriptine-resistant prolactinomas .Mol Cell Endocrinol. 2014 Sep;395(1-2):10-8. doi: 10.1016/j.mce.2014.07.014. Epub 2014 Jul 23. 10.1016/j.mce.2014.07.014