Drug Information

Drug (ID: DG00314) and It's Reported Resistant Information

• Name: Mitotane
• Synonyms: Chloditan; Chlodithan; Chlodithane; Khloditan; Khlodithan; Lysodren; Mitotan; Mitotano; Mitotanum; Mytotan; Bristol Myers Squibb Brand of Mitotane; C 3010; CB 313; CB313; PS694_SUPELCO; Bristol-Myers Squibb Brand of Mitotane; CB-313; Lysodren (TN); Mitotano [INN-Spanish]; Mitotanum [INN-Latin]; Ortho,para DDD; Mitotane [USAN:INN:JAN]; O,p-DDD; O,p-Tde; Ortho,para-DDD; Mitotane (JAN/USP/INN); O,p'-DDD; O,p'-Dichlorodiphenyldichloroethane; O,p'-TDE; Ethane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-(8CI); (+-)-1,1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane; (2,4'-Dichlorodiphenyl)dichloroethane; (o,p)-DDD; 1,1-Dichloro-2,2-bis(2,4'-dichlorophenyl)ethane; 1,1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane; 1,1-Dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane; 1-(2-Chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane; 1-Chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)benzene; 1-Chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene; 2,2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane; 2,4'-Ddd; 2,4'-Dichlorodiphenyldichloroethane; 2,4'-Dichlorophenyldichlorethane; 2-(2-Chlorophenyl)-2-(4-chlorophenyl)-1,1-dichloroethane; 2-(o-Chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloroethane
• Indication:
  In total 1 Indication(s)
  Adrenal cancer [ICD-11: 2D11]; Approved; [1]
• Target: Estrogen receptor (ESR); ESR1_HUMAN; [1]
• Formula: C14H10Cl4
• IsoSMILES: C1=CC=C(C(=C1)C(C2=CC=C(C=C2)Cl)C(Cl)Cl)Cl
• InChI: 1S/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H
• InChIKey: JWBOIMRXGHLCPP-UHFFFAOYSA-N
• PubChem CID: 4211
• ChEBI ID: CHEBI:6954
• TTD Drug ID: D0Z5OE
• DrugBank ID: DB00648

Type(s) of Resistant Mechanism of This Drug

  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

Breast cancer [ICD-11: 2C60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-431 [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: H295R cells; Kidney; Homo sapiens (Human); CVCL_0458
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Cell Growth Assay; Flow cytometry assay
• Mechanism Description: Restoration of miR-431 in vitro decreased the half maximal inhibitory concentrations of doxorubicin and mitotane, with markedly increased apoptosis via downregulating ZEB1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: H295R cells; Kidney; Homo sapiens (Human); CVCL_0458
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: Cell Growth Assay; Flow cytometry assay
• Mechanism Description: Restoration of miR-431 in vitro decreased the half maximal inhibitory concentrations of doxorubicin and mitotane, with markedly increased apoptosis via downregulating ZEB1.

References

• Ref 1: microRNA-431 as a Chemosensitizer and Potentiator of Drug Activity in Adrenocortical Carcinoma. Oncologist. 2019 Jun;24(6):e241-e250. doi: 10.1634/theoncologist.2018-0849. Epub 2019 Mar 27.