Drug Information

Drug (ID: DG00198) and It's Reported Resistant Information
Name
Celastrol
Synonyms
Tripterin; Tripterine; Celastrol, Celastrus scandens; (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxylic acid; (2R,4aS,6aS,12bR,14aS,14bR)-10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylic acid; 3-Hydroxy-24-nor-2-oxo-1(10),3,5,7-friedelatetraen-29-oic Acid
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Indication
In total 1 Indication(s)
Motor neuron disease [ICD-11: 8B60]
Preclinical
[1]
Structure
Target Interleukin-1 beta (IL1B) IL1B_HUMAN [1]
Tumor necrosis factor (TNF) TNFA_HUMAN [1]
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Formula
C29H38O4
IsoSMILES
CC1=C(C(=O)C=C2C1=CC=C3[C@]2(CC[C@@]4([C@@]3(CC[C@@]5([C@H]4C[C@](CC5)(C)C(=O)O)C)C)C)C)O
InChI
1S/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1
InChIKey
KQJSQWZMSAGSHN-JJWQIEBTSA-N
PubChem CID
122724
ChEBI ID
CHEBI:63959
TTD Drug ID
D0I9XH
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  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
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Lung cancer [ICD-11: 2C25]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-33a-5p [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
LTEP-a-2 cells Lung Homo sapiens (Human) CVCL_6929
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Combination of celastrol and miR-33a-5p increases the expression of miR-33a-5p to inhibit the mTOR signaling pathway.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
LTEP-a-2 cells Lung Homo sapiens (Human) CVCL_6929
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description Combination of celastrol and miR-33a-5p increases the expression of miR-33a-5p to inhibit the mTOR signaling pathway.
Melanoma [ICD-11: 2C30]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-217 [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
In Vitro Model SNU387 cells Liver Homo sapiens (Human) CVCL_0250
Malme3M cells Skin Homo sapiens (Human) CVCL_1438
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-326, which forms a negative feedback regulatory loop with HDAC3, regulates the invasion and the metastatic potential of cancer cells and tumor-induced angiogenesis in response to anti-cancer drugs. miR-200b, miR-217, and miR-335, which form a positive feedback loop with HDAC3, confer sensitivity to anti-cancer drugs. We show that CAGE, reported to form a feedback loop with miR-200b, serves as a downstream target of HDAC3 and miR-326. In this study, we show that the regulation of the miR-326/HDAC3 axis can be employed for the development of anti-cancer therapeutics.
Key Molecule: hsa-mir-335 [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
In Vitro Model SNU387 cells Liver Homo sapiens (Human) CVCL_0250
Malme3M cells Skin Homo sapiens (Human) CVCL_1438
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-326, which forms a negative feedback regulatory loop with HDAC3, regulates the invasion and the metastatic potential of cancer cells and tumor-induced angiogenesis in response to anti-cancer drugs. miR-200b, miR-217, and miR-335, which form a positive feedback loop with HDAC3, confer sensitivity to anti-cancer drugs. We show that CAGE, reported to form a feedback loop with miR-200b, serves as a downstream target of HDAC3 and miR-326. In this study, we show that the regulation of the miR-326/HDAC3 axis can be employed for the development of anti-cancer therapeutics.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: hsa-mir-200b [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model SNU387 cells Liver Homo sapiens (Human) CVCL_0250
Malme3M cells Skin Homo sapiens (Human) CVCL_1438
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-326, which forms a negative feedback regulatory loop with HDAC3, regulates the invasion and the metastatic potential of cancer cells and tumor-induced angiogenesis in response to anti-cancer drugs. miR-200b, miR-217, and miR-335, which form a positive feedback loop with HDAC3, confer sensitivity to anti-cancer drugs. We show that CAGE, reported to form a feedback loop with miR-200b, serves as a downstream target of HDAC3 and miR-326. In this study, we show that the regulation of the miR-326/HDAC3 axis can be employed for the development of anti-cancer therapeutics.
Key Molecule: hsa-miR-326 [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
In Vitro Model SNU387 cells Liver Homo sapiens (Human) CVCL_0250
Malme3M cells Skin Homo sapiens (Human) CVCL_1438
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-326, which forms a negative feedback regulatory loop with HDAC3, regulates the invasion and the metastatic potential of cancer cells and tumor-induced angiogenesis in response to anti-cancer drugs. miR-200b, miR-217, and miR-335, which form a positive feedback loop with HDAC3, confer sensitivity to anti-cancer drugs. We show that CAGE, reported to form a feedback loop with miR-200b, serves as a downstream target of HDAC3 and miR-326. In this study, we show that the regulation of the miR-326/HDAC3 axis can be employed for the development of anti-cancer therapeutics.
References
Ref 1 miR-33a-5p enhances the sensitivity of lung adenocarcinoma cells to celastrol by regulating mTOR signaling. Int J Oncol. 2018 Apr;52(4):1328-1338. doi: 10.3892/ijo.2018.4276. Epub 2018 Feb 14.
Ref 2 miR-326-histone deacetylase-3 feedback loop regulates the invasion and tumorigenic and angiogenic response to anti-cancer drugs. J Biol Chem. 2014 Oct 3;289(40):28019-39. doi: 10.1074/jbc.M114.578229. Epub 2014 Aug 19.

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