Natural Product (NP) Details
| General Information of the NP (ID: NP5891) | |||||
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| Name |
Pristimerin
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| Synonyms |
Celastrol-methylether; Pristimerine; GNF-PF-476; UNII-28ZK7PR57S; CHEBI:8416; Celastrol methyl ester; 28ZK7PR57S; MFCD01711331; methyl (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-carboxylate; (9b,13a,14b,20a)-3-Hydroxy-9,13-dimethyl-2-oxo-24,25,26 -trinoroleana-1(10),3,5,7-tertraen-29-oic acid methyl ester; C30H40O4; methyl (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-carboxylate; Spectrum_001558; SpecPlus_000649; Spectrum2_000546; Spectrum3_001651; Spectrum4_001681; Spectrum5_000322; 24-Nor-D:A-friedooleana-1(10),3,5,7-tetraen-29-oic acid, 3-hydroxy-2-oxo-, methyl ester; SCHEMBL15020; BSPBio_003401; KBioGR_001942; KBioSS_002038; CHEMBL54804; DivK1c_006745; SPECTRUM1504181; SPBio_000591; MEGxp0_000269; DTXSID5044027; ACon0_000836; KBio1_001689; KBio2_002038; KBio2_004606; KBio2_007174; KBio3_002621; HY-N1937; ZINC4097723; BDBM50481947; CCG-38723; s9404; AKOS032960306; CS-6257; SDCCGMLS-0066814.P001; NCGC00178090-01; NCGC00178090-03; B7488; X1210; C08633; Q-100112; Q27108073; (9?,13?,14?,20?)-3-Hydroxy-9,13-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid methyl ester; D:A-Friedo-24-noroleana-1(10),3,5,7-tetraen-29-oic acid, 3-hydroxy-2-oxo-, methyl ester, (20alpha)- (9CI)
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| Species Origin | Pristimera indica ... | Click to Show/Hide | |||
| Pristimera indica | |||||
| Primula elatior | |||||
| Maytenus canariensis | |||||
| Disease | Colorectal cancer [ICD-11: 2B91] | Investigative | [1] | ||
| Structure |
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Click to Download Mol2D MOL |
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| ADMET Property |
Absporption
Caco-2 Permeability
-5.133
MDCK Permeability
-4.906
PAMPA
++
HIA
- - -
Distribution
VDss
0.242
PPB
93%
BBB
+++
Metabolism
CYP1A2 inhibitor
++
CYP1A2 substrate
++
CYP2C19 inhibitor
+++
CYP2C19 substrate
- - -
CYP2C9 inhibitor
+
CYP2C9 substrate
- - -
CYP2D6 inhibitor
- - -
CYP2D6 substrate
- - -
CYP3A4 inhibitor
++
CYP3A4 substrate
+++
CYP2B6 inhibitor
+++
CYP2B6 substrate
- - -
CYP2C8 inhibitor
+++
HLM Stability
+++
Excretion
CLplasma
4.754
T1/2
0.535
Toxicity
DILI
+++
Rat Oral Acute Toxicity
++
FDAMDD
++
Respiratory
+++
Human Hepatotoxicity
++
Ototoxicity
++
Drug-induced Nephrotoxicity
+++
Drug-induced Neurotoxicity
++
Hematotoxicity
++
Genotoxicity
+++
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++).
2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | |||||
| Formula |
C30H40O4
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| PubChem CID | |||||
| Canonical SMILES |
CC1=C(C(=O)C=C2C1=CC=C3C2(CCC4(C3(CCC5(C4CC(CC5)(C)C(=O)OC)C)C)C)C)O
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| InChI |
1S/C30H40O4/c1-18-19-8-9-22-28(4,20(19)16-21(31)24(18)32)13-15-30(6)23-17-27(3,25(33)34-7)11-10-26(23,2)12-14-29(22,30)5/h8-9,16,23,32H,10-15,17H2,1-7H3/t23-,26-,27-,28+,29-,30+/m1/s1
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| InChIKey |
JFACETXYABVHFD-WXPPGMDDSA-N
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| CAS Number |
CAS 1258-84-0
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| Herb ID | |||||
| SymMap ID | |||||
| TCMSP ID | |||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP | ||||||
| Gemcitabine | Solid tumour/cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | CHK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | TP53BP1 | Molecule Info |
Pathway MAP
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| In-vitro Model | AsPC-1 | CVCL_0152 | Pancreatic ductal adenocarcinoma | Homo sapiens | ||
| BxPC-3 | CVCL_0186 | Pancreatic ductal adenocarcinoma | Homo sapiens | |||
| PANC-1 | CVCL_0480 | Pancreatic ductal adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Pristimerin synergizes with gemcitabine through abrogating Chk1/53BP1-mediated DNA repair in pancreatic cancer cells. | |||||
| Target and Pathway | ||||
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| Target(s) | Stress-activated protein kinase JNK1 (JNK1) | Molecule Info | [3] | |
| Stress-activated protein kinase JNK2 (JNK2) | Molecule Info | [3] | ||
| KEGG Pathway | MAPK signaling pathway | Click to Show/Hide | ||
| 2 | ErbB signaling pathway | |||
| 3 | Ras signaling pathway | |||
| 4 | cAMP signaling pathway | |||
| 5 | FoxO signaling pathway | |||
| 6 | Sphingolipid signaling pathway | |||
| 7 | Protein processing in endoplasmic reticulum | |||
| 8 | Wnt signaling pathway | |||
| 9 | Osteoclast differentiation | |||
| 10 | Focal adhesion | |||
| 11 | Toll-like receptor signaling pathway | |||
| 12 | NOD-like receptor signaling pathway | |||
| 13 | RIG-I-like receptor signaling pathway | |||
| 14 | Fc epsilon RI signaling pathway | |||
| 15 | TNF signaling pathway | |||
| 16 | Neurotrophin signaling pathway | |||
| 17 | Retrograde endocannabinoid signaling | |||
| 18 | Dopaminergic synapse | |||
| 19 | Inflammatory mediator regulation of TRP channels | |||
| 20 | Insulin signaling pathway | |||
| 21 | GnRH signaling pathway | |||
| 22 | Progesterone-mediated oocyte maturation | |||
| 23 | Prolactin signaling pathway | |||
| 24 | Adipocytokine signaling pathway | |||
| 25 | Type II diabetes mellitus | |||
| 26 | Non-alcoholic fatty liver disease (NAFLD) | |||
| 27 | Epithelial cell signaling in Helicobacter pylori infection | |||
| 28 | Shigellosis | |||
| 29 | Salmonella infection | |||
| 30 | Pertussis | |||
| 31 | Chagas disease (American trypanosomiasis) | |||
| 32 | Toxoplasmosis | |||
| 33 | Tuberculosis | |||
| 34 | Hepatitis C | |||
| 35 | Hepatitis B | |||
| 36 | Influenza A | |||
| 37 | HTLV-I infection | |||
| 38 | Herpes simplex infection | |||
| 39 | Epstein-Barr virus infection | |||
| 40 | Pathways in cancer | |||
| 41 | Colorectal cancer | |||
| 42 | Pancreatic cancer | |||
| 43 | Choline metabolism in cancer | |||
| 44 | T cell receptor signaling pathway | |||
| NetPath Pathway | IL5 Signaling Pathway | Click to Show/Hide | ||
| 2 | TNFalpha Signaling Pathway | |||
| Panther Pathway | Alzheimer disease-amyloid secretase pathway | Click to Show/Hide | ||
| 2 | Angiogenesis | |||
| 3 | Apoptosis signaling pathway | |||
| 4 | B cell activation | |||
| 5 | FAS signaling pathway | |||
| 6 | Integrin signalling pathway | |||
| 7 | Interferon-gamma signaling pathway | |||
| 8 | Oxidative stress response | |||
| 9 | PDGF signaling pathway | |||
| 10 | Parkinson disease | |||
| 11 | TGF-beta signaling pathway | |||
| 12 | T cell activation | |||
| 13 | Toll receptor signaling pathway | |||
| 14 | Ras Pathway | |||
| 15 | CCKR signaling map ST | |||
| 16 | Huntington disease | |||
| Pathwhiz Pathway | Intracellular Signalling Through Adenosine Receptor A2a and Adenosine | Click to Show/Hide | ||
| 2 | Intracellular Signalling Through Adenosine Receptor A2b and Adenosine | |||
| 3 | Fc Epsilon Receptor I Signaling in Mast Cells | |||
| Pathway Interaction Database | Fc-epsilon receptor I signaling in mast cells | Click to Show/Hide | ||
| 2 | Endothelins | |||
| 3 | BCR signaling pathway | |||
| 4 | RhoA signaling pathway | |||
| 5 | Noncanonical Wnt signaling pathway | |||
| 6 | CD40/CD40L signaling | |||
| 7 | Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) | |||
| 8 | Osteopontin-mediated events | |||
| 9 | Reelin signaling pathway | |||
| 10 | TRAIL signaling pathway | |||
| 11 | CDC42 signaling events | |||
| 12 | Signaling events regulated by Ret tyrosine kinase | |||
| 13 | Angiopoietin receptor Tie2-mediated signaling | |||
| 14 | FAS (CD95) signaling pathway | |||
| 15 | IL1-mediated signaling events | |||
| 16 | Role of Calcineurin-dependent NFAT signaling in lymphocytes | |||
| 17 | Glucocorticoid receptor regulatory network | |||
| 18 | IL2-mediated signaling events | |||
| 19 | Rapid glucocorticoid signaling | |||
| 20 | FoxO family signaling | |||
| 21 | Ceramide signaling pathway | |||
| 22 | Regulation of Androgen receptor activity | |||
| 23 | p75(NTR)-mediated signaling | |||
| 24 | ErbB1 downstream signaling | |||
| 25 | ATF-2 transcription factor network | |||
| 26 | ErbB2/ErbB3 signaling events | |||
| 27 | PDGFR-beta signaling pathway | |||
| 28 | JNK signaling in the CD4+ TCR pathway | |||
| 29 | Nephrin/Neph1 signaling in the kidney podocyte | |||
| 30 | HIV-1 Nef: Negative effector of Fas and TNF-alpha | |||
| 31 | Retinoic acid receptors-mediated signaling | |||
| 32 | Signaling events mediated by Stem cell factor receptor (c-Kit) | |||
| 33 | EPO signaling pathway | |||
| 34 | Syndecan-2-mediated signaling events | |||
| 35 | Ephrin B reverse signaling | |||
| 36 | p53 pathway | |||
| 37 | N-cadherin signaling events | |||
| 38 | S1P2 pathway | |||
| 39 | Downstream signaling in naï | |||
| 40 | ||||
| 41 | RAC1 signaling pathway | |||
| 42 | Signaling events mediated by focal adhesion kinase | |||
| 43 | Glypican 3 network | |||
| 44 | IL12 signaling mediated by STAT4 | |||
| 45 | Regulation of retinoblastoma protein | |||
| Reactome | NRAGE signals death through JNK | Click to Show/Hide | ||
| 2 | NRIF signals cell death from the nucleus | |||
| 3 | Oxidative Stress Induced Senescence | |||
| 4 | FCERI mediated MAPK activation | |||
| 5 | DSCAM interactions | |||
| 6 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 | |||
| 7 | Activation of the AP-1 family of transcription factors | |||
| 8 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks | |||
| WikiPathways | Toll-like receptor signaling pathway | Click to Show/Hide | ||
| 2 | DNA Damage Response (only ATM dependent) | |||
| 3 | TCR Signaling Pathway | |||
| 4 | ErbB Signaling Pathway | |||
| 5 | Insulin Signaling | |||
| 6 | EGF/EGFR Signaling Pathway | |||
| 7 | MAPK Signaling Pathway | |||
| 8 | TGF beta Signaling Pathway | |||
| 9 | FAS pathway and Stress induction of HSP regulation | |||
| 10 | Signaling of Hepatocyte Growth Factor Receptor | |||
| 11 | Kit receptor signaling pathway | |||
| 12 | Transcriptional activation by NRF2 | |||
| 13 | NLR Proteins | |||
| 14 | IL-3 Signaling Pathway | |||
| 15 | Cardiac Hypertrophic Response | |||
| 16 | Nanoparticle-mediated activation of receptor signaling | |||
| 17 | Structural Pathway of Interleukin 1 (IL-1) | |||
| 18 | EBV LMP1 signaling | |||
| 19 | JAK/STAT | |||
| 20 | PDGF Pathway | |||
| 21 | Nanoparticle triggered regulated necrosis | |||
| 22 | BDNF signaling pathway | |||
| 23 | Integrated Pancreatic Cancer Pathway | |||
| 24 | Oncostatin M Signaling Pathway | |||
| 25 | Corticotropin-releasing hormone | |||
| 26 | AGE/RAGE pathway | |||
| 27 | TNF alpha Signaling Pathway | |||
| 28 | B Cell Receptor Signaling Pathway | |||
| 29 | Prostate Cancer | |||
| 30 | TSLP Signaling Pathway | |||
| 31 | TWEAK Signaling Pathway | |||
| 32 | Leptin signaling pathway | |||
| 33 | RANKL/RANK Signaling Pathway | |||
| 34 | Signalling by NGF | |||
| 35 | IL-1 signaling pathway | |||
| 36 | Intrinsic Pathway for Apoptosis | |||
| 37 | DSCAM interactions | |||
| 38 | Apoptosis Modulation and Signaling | |||
| 39 | Type II diabetes mellitus | |||
| 40 | MicroRNAs in cardiomyocyte hypertrophy | |||
| 41 | Physiological and Pathological Hypertrophy of the Heart | |||
| 42 | Regulation of toll-like receptor signaling pathway | |||
| 43 | Osteoclast Signaling | |||
| 44 | TGF Beta Signaling Pathway | |||
| 45 | Wnt Signaling Pathway | |||
| 46 | Wnt Signaling Pathway and Pluripotency | |||
| 47 | ATM Signaling Pathway | |||
