Drug Information

Drug (ID: DG00090) and It's Reported Resistant Information

• Name: Hydroxycamptothecin
• Synonyms: 10-Hydroxycamptothecin; 19685-09-7; (S)-10-Hydroxycamptothecin; Hydroxycamptothecin; 10-hydroxycamptothecine; 10-Hydroxy camptothecin; Hydroxycamptothecine; Camptothecin, hydroxy-; 10-Hydroxy-Camptothecin; (S)-4-Ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; Camptothecin, 10-hydroxy-; Camptothecine, 10-hydroxy-; UNII-9Z01632KRV; NSC 107124; HCPT; (4S)-4-Ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; (S)-10-Hydroxycamptothecin hydrate; NSC107124
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Bladder cancer [ICD-11: 2C94]; [1]
  Colon cancer [ICD-11: 2B90]; [2]
• Target: DNA topoisomerase I (TOP1); TOP1_HUMAN; [1]
• Formula: C20H16N2O5
• IsoSMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C3=C2)N=C5C=CC(=CC5=C4)O)O
• InChI: 1S/C20H16N2O5/c1-2-20(26)14-7-16-17-11(5-10-6-12(23)3-4-15(10)21-17)8-22(16)18(24)13(14)9-27-19(20)25/h3-7,23,26H,2,8-9H2,1H3/t20-/m0/s1
• InChIKey: HAWSQZCWOQZXHI-FQEVSTJZSA-N
• PubChem CID: 97226
• ChEBI ID: CHEBI:81395
• TTD Drug ID: D07ILP
• VARIDT ID: DR01489
• DrugBank ID: DB12385

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Colon cancer [ICD-11: 2B90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-506 [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vitro Model: SW1116/HCPT; Colon; Homo sapiens (Human); CVCL_0544
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARalpha expression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Peroxisome proliferator-activated receptor alpha (PPARA) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vitro Model: SW1116/HCPT; Colon; Homo sapiens (Human); CVCL_0544
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARalpha expression.

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 G2 (ABCG2) [3]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MMP16 is one member of the matrix metalloproteinase (MMP) family and can degrade type III collagen, gelatin, fibronectin and laminin-1, enhance the growth and invasiveness. ABCG2 is a member of ATP-binding cassette transporters. miR-328 downregulation may contribute to the overexpression of ABCG2 and MMP16 and cause drug resistance.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: hsa-mir-328 [3]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MMP16 is one member of the matrix metalloproteinase (MMP) family and can degrade type III collagen, gelatin, fibronectin and laminin-1, enhance the growth and invasiveness. ABCG2 is a member of ATP-binding cassette transporters. miR-328 downregulation may contribute to the overexpression of ABCG2 and MMP16 and cause drug resistance.

Key Molecule: Matrix metalloproteinase-16 (MMP16) [3]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: MMP16 is one member of the matrix metalloproteinase (MMP) family and can degrade type III collagen, gelatin, fibronectin and laminin-1, enhance the growth and invasiveness. ABCG2 is a member of ATP-binding cassette transporters. miR-328 downregulation may contribute to the overexpression of ABCG2 and MMP16 and cause drug resistance.

Bladder cancer [ICD-11: 2C94]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-22-3p [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: UM-UC-3 cells; Bladder; Homo sapiens (Human); CVCL_1783
• In Vitro Model: H-bc cells; Bladder; Homo sapiens (Human); CVCL_BT00
• In Vitro Model: HTB-1 cells; Bladder; Homo sapiens (Human); CVCL_0359
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Neuroepithelial cell-transforming gene 1 protein (NET1) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vitro Model: UM-UC-3 cells; Bladder; Homo sapiens (Human); CVCL_1783
• In Vitro Model: H-bc cells; Bladder; Homo sapiens (Human); CVCL_BT00
• In Vitro Model: HTB-1 cells; Bladder; Homo sapiens (Human); CVCL_0359
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells.

References

• Ref 1: miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells. Oncol Rep. 2018 Jun;39(6):2731-2740. doi: 10.3892/or.2018.6355. Epub 2018 Apr 4.
• Ref 2: MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells. FEBS Lett. 2011 Nov 16;585(22):3560-8. doi: 10.1016/j.febslet.2011.10.021. Epub 2011 Oct 22.
• Ref 3: MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer. Br J Cancer. 2012 Mar 27;106(7):1320-30. doi: 10.1038/bjc.2012.88.