Drug Information

Drug (ID: DG00124) and It's Reported Resistant Information

• Name: Colchicine
• Synonyms: Colchicin; Colchicina; Colchicinum; Colchineos; Colchisol; Colchysat; Colcin; Colcrys; Colsaloid; Colstat; Condylon; Goutnil; Kolkicin; LOC; Binds to tubulin; Colchicin [German]; Colchicina [Italian]; Colchicine [JAN]; Inhibits microtubular assembly; Spindle poison; C 9754; Colchicine (TN); Colchicine, Colchicum autumnale; MPC-004; N-Acetyl trimethylcolchicinic acid methylether; Colchicine (JP15/USP); Colchicine, (R)-Isomer; Benzo(a)heptalen-9(5H)-one; Colchicine, (+-)-Isomer; N-(5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)acetamide; N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide; N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide; N-[(7S)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamide; N-(5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[.alpha.]heptalen-7-yl)-acetamide; N-((7S)-5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo(a)heptalen-7-yl)-acetamide; (S)-N-(5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl)acetamide; 7-alpha-H-Colchicine; 7.alpha.H-Colchicine; 7alphaH-Colchicine
• Indication:
  In total 1 Indication(s)
  Gout [ICD-11: FA25]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  Pituitary cancer [ICD-11: 2F37]; [2]
• Target: Tubulin (TUB); NOUNIPROTAC; [1]
• Formula: C22H25NO6
• IsoSMILES: CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC
• InChI: 1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m0/s1
• InChIKey: IAKHMKGGTNLKSZ-INIZCTEOSA-N
• PubChem CID: 6167
• ChEBI ID: CHEBI:27882
• TTD Drug ID: D09DHY
• DrugBank ID: DB01394

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [3]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Colorectal carcinoma [ICD-11: 2B91.3]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• In Vitro Model: HCT-8 cells; Colon; Homo sapiens (Human); CVCL_2478
• In Vitro Model: NIH-G185 cells; Ovary; Homo sapiens (Human); CVCL_L991
• In Vitro Model: NIH 3T3 cells; Colon; Homo sapiens (Human); CVCL_0594
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: G185 cells were 27-135 fold more resistant to the cytotoxic drugs doxorubicin, vinblastine, colchicine and paclitaxel than the parental NIH 3T3 cells. Co-administration of TPGS enhanced the cytotoxicity of doxorubicin, vinblastine, paclitaxel, and colchicine in the G185 cells to levels comparable to the parental.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-106b~25 [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR106b~25 cluster/EP300/E-cadherin signaling pathway; Regulation; hsa05206
• In Vitro Model: MTMECs cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Histone acetyltransferase p300 (EP300) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR106b~25 cluster/EP300/E-cadherin signaling pathway; Regulation; hsa05206
• In Vitro Model: MTMECs cells; Breast; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.

Pituitary cancer [ICD-11: 2F37]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

References

• Ref 1: MiR-106b~25 cluster regulates multidrug resistance in an ABC transporter-independent manner via downregulation of EP300. Oncol Rep. 2016 Feb;35(2):1170-8. doi: 10.3892/or.2015.4412. Epub 2015 Nov 12.
• Ref 2: Characterization of multidrug-resistant pituitary tumor cells .Endocrinology. 1992 Jun;130(6):3246-56. doi: 10.1210/endo.130.6.1350759. 10.1210/endo.130.6.1350759
• Ref 3: Inhibition of P-glycoprotein by D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Pharm Res. 1999 Oct;16(10):1550-6. doi: 10.1023/a:1015000503629.