Natural Product: NPC185738

Natural Product IDNPC185738
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tetramethoxycurcumin
IUPAC Name (1E,6E)-1,7-bis(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5-dione
Synonyms Di-O-Methylcurcumin; Tetramethoxycurcumin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL261295
PubChem CID 9952605
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids
          • [CHEMONTID:0000356] Curcuminoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey HMJSBVCDPKODEX-NXZHAISVSA-N
Standard InCHI InChI=1S/C23H24O6/c1-26-20-11-7-16(13-22(20)28-3)5-9-18(24)15-19(25)10-6-17-8-12-21(27-2)23(14-17)29-4/h5-14H,15H2,1-4H3/b9-5+,10-6+
SMILES COc1ccc(/C=C/C(=O)CC(=O)/C=C/c2ccc(c(c2)OC)OC)cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   396.16 Volume:   415.628
?
Van der Waals volume.
Dense:   0.953 LogP:   2.582
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.015
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.078
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   16.0
TPSA:   71.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.447 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.262 Fsp3:   0.217
MCE-18:   14.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.994 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.279
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.798
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.6 Promiscuous compounds:   0.013

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.883 MDCK Permeability:   -4.608
Pgp-inhibitor:   0.997 Pgp-substrate:   0.002
PAMPA:   0.003
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.145
20% Bioavailability (F20%):   0.652 30% Bioavailability (F30%):   0.209
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.052
Plasma Protein Binding (PPB):   93.877% Volume Distribution (VD):   -0.268
Fu: 5.738%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.975
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.014 CYP1A2-substrate:   0.134
CYP2C19-inhibitor:   0.77 CYP2C19-substrate:   0.096
CYP2C9-inhibitor:   0.031 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.993 CYP2D6-substrate:   0.115
CYP3A4-inhibitor:   0.483 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.645
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  8.555 Half-life (T1/2):  0.866

ADMET: Toxicity

hERG Blockers:  0.547 hERG Blockers (10um):  0.634
Human Hepatotoxicity (H-HT):  0.46 Drug-induced Liver Injury (DILI):  0.095
AMES Toxicity:  0.3 Rat Oral Acute Toxicity:  0.159
Maximum Recommended Daily Dose:  0.321 Skin Sensitization:  0.958
Carcinogencity:  0.335 Eye Corrosion:  0.192
Eye Irritation:  0.821 Respiratory Toxicity:  0.749
Drug-induced Neurotoxicity:  0.676 Ototoxicity:  0.107
Hematotoxicity:  0.125 Drug-induced Nephrotoxicity:  0.287
Genotoxicity:  0.025 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.25 Hek293 Cytotoxicity:  0.434
BCF:   1.032
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.006
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.155
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.764
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12350137]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota rhizome n.a. n.a. PMID[12617587]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[23153397]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. leaf n.a. PMID[23901173]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[28068085]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9584408]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizome Essent. Oil n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 35.7 n.a. PMID[29223100]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens EC50 = 16600.0 nM PMID[29223100]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT134 Cell line SK-BR-3 Homo sapiens IC50 = 955.0 nM PMID[19019687]
NPT83 Cell line MCF7 Homo sapiens IC50 = 1070.0 nM PMID[19019687]
NPT71 Cell line HEK293 Homo sapiens EC50 = 200000.0 nM PMID[20004045]
NPT71 Cell line HEK293 Homo sapiens CC50 > 20000.0 nM PMID[36608774]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 7860.0 nM PMID[18194869]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum MIC = 29600.0 nM PMID[18194869]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum MIC = 29100.0 nM PMID[18194869]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 8400.0 nM PMID[18194869]
NPT115 Organism Mycobacterium tuberculosis H37Ra Mycobacterium tuberculosis H37Ra MIC = 100.0 ug.mL-1 PMID[20691508]
NPT1018 Organism Trypanosoma brucei Trypanosoma brucei EC50 > 4000.0 nM PMID[36608774]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 = 450.0 nM PMID[20004045]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 = 620.0 nM PMID[20004045]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 = 770.0 nM PMID[20004045]
NPT841 Organism Leishmania major Leishmania major EC50 = 2800.0 nM PMID[20004045]
NPT842 Organism Leishmania mexicana Leishmania mexicana EC50 = 10000.0 nM PMID[20004045]
NPT2 Others Unspecified n.a. Ratio EC50 = 70.0 n.a. PMID[20004045]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC185738 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.697 Remote Similarity NPC310905
0.6571 Remote Similarity NPC179309
0.6216 Remote Similarity NPC227894
0.6047 Remote Similarity NPC280001
0.6 Remote Similarity NPC56332
0.5854 Remote Similarity NPC160900
0.5789 Remote Similarity NPC245552
0.5556 Remote Similarity NPC175298
0.5429 Remote Similarity NPC179726
0.5333 Remote Similarity NPC71941
0.5217 Remote Similarity NPC106659
0.5128 Remote Similarity NPC123948
0.5128 Remote Similarity NPC96122
0.5122 Remote Similarity NPC294941
0.5116 Remote Similarity NPC258171
0.5102 Remote Similarity NPC47194

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC185738 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
1.0 High Similarity NPD5536 Phase 2
0.5854 Remote Similarity NPD4379 Clinical (unspecified phase)

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data