Drug (ID: DG00255) and It's Reported Resistant Information
Name
Leucovorin
Indication
In total 1 Indication(s)
Discovery agent [ICD-11: N.A.]
Investigative
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
Colorectal cancer [ICD-11: 2B91]
[2]
Neuroendocrine carcinoma [ICD-11: 2D4Y]
[3]
Target Proton-coupled folate transporter (SLC46A1) PCFT_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C20H23N7O7
IsoSMILES
C1C(N(C2=C(N1)N=C(NC2=O)N)C=O)CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
InChI
1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)/t12 ,13-/m0/s1
InChIKey
VVIAGPKUTFNRDU-ABLWVSNPSA-N
PubChem CID
135403648
ChEBI ID
CHEBI:15640
TTD Drug ID
D0R4PS
VARIDT ID
DR00238
DrugBank ID
DB00650
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  RTDM: Regulation by the Disease Microenvironment
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Colorectal cancer [ICD-11: 2B91]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-19a [2]
Molecule Alteration Expression
Up-regulation
Resistant Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
Response evaluation criteria in solid tumors assay
Mechanism Description Aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: hsa-mir-218 [1]
Molecule Alteration Expression
Up-regulation
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
FHC cells Colon Homo sapiens (Human) CVCL_3688
SW620 cells Colon Homo sapiens (Human) CVCL_0547
Experiment for
Molecule Alteration
RT-PCR; qRT-PCR
Experiment for
Drug Resistance
Boyden chambers cell migration and invasion assays
Mechanism Description miR218 is a tumor-suppressor gene and could significantly suppress the EMT process, miR218 promoted cell apoptosis and enhanced 5-FU-based chemosensitivity in colorectal cancer cells by targeting BIRC5.
References
Ref 1 MALAT1 Is Associated with Poor Response to Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients and Promotes Chemoresistance through EZH2. Mol Cancer Ther. 2017 Apr;16(4):739-751. doi: 10.1158/1535-7163.MCT-16-0591. Epub 2017 Jan 9.
Ref 2 Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal cancer cases. Asian Pac J Cancer Prev. 2013;14(12):7421-6. doi: 10.7314/apjcp.2013.14.12.7421.
Ref 3 Benefit of rebiopsy for deciding treatment strategy in rectal cancer: A case reportOncol Lett. 2017 Sep;14(3):3697-3700. doi: 10.3892/ol.2017.6601. Epub 2017 Jul 18.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Zhang.