Natural Product: NPC70843

Natural Product IDNPC70843
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,2-Dihydrobis(De-O-Methyl)-Curcumin
IUPAC Name (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL448759
PubChem CID 10614892
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 XLKHKZCPVAHTFN-YLMKKNOUSA-N
Standard InCHI InChI=1S/C19H18O4/c20-16-7-1-14(2-8-16)5-11-18(22)13-19(23)12-6-15-3-9-17(21)10-4-15/h1-5,7-11,13,20-22H,6,12H2/b11-5+,18-13-
SMILES c1cc(ccc1/C=C/C(=C/C(=O)CCc1ccc(cc1)O)/O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.12 Volume:   331.5
?
Van der Waals volume.
Dense:   0.936 LogP:   3.138
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.008
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.813
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   15.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.431 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.439 Fsp3:   0.105
MCE-18:   12.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.958 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.529
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.811 Promiscuous compounds:   0.304

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.904 MDCK Permeability:   -4.806
Pgp-inhibitor:   0.141 Pgp-substrate:   0.002
PAMPA:   0.822
?
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):   0.001
20% Bioavailability (F20%):   0.846 30% Bioavailability (F30%):   0.973
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.002
Plasma Protein Binding (PPB):   95.919% Volume Distribution (VD):   -0.458
Fu: 3.172%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.009
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.024 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.366
CYP2C9-inhibitor:   0.036 CYP2C9-substrate:   0.209
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.154
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.344
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.409
?
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):  9.123 Half-life (T1/2):  1.004

ADMET: Toxicity

hERG Blockers:  0.148 hERG Blockers (10um):  0.222
Human Hepatotoxicity (H-HT):  0.839 Drug-induced Liver Injury (DILI):  0.376
AMES Toxicity:  0.341 Rat Oral Acute Toxicity:  0.107
Maximum Recommended Daily Dose:  0.583 Skin Sensitization:  0.953
Carcinogencity:  0.381 Eye Corrosion:  0.071
Eye Irritation:  0.991 Respiratory Toxicity:  0.555
Drug-induced Neurotoxicity:  0.288 Ototoxicity:  0.388
Hematotoxicity:  0.072 Drug-induced Nephrotoxicity:  0.523
Genotoxicity:  0.432 RPMI-8226 Immunitoxicity:  0.027
A549 Cytotoxicity:  0.089 Hek293 Cytotoxicity:  0.629
BCF:   1.317
?
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:   3.933
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.566
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.38
?
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
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota seeds Mengha, Yunnan Province, China 1991-Aug PMID[11277741]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota seeds n.a. n.a. PMID[11325233]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota Seeds n.a. n.a. PMID[11430002]
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]
NPO33355 aframomum letestuianum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12662093]
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]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9461664]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9584408]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
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]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
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]
NPO6836 Alpinia blepharocalyx 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT453 Cell line HT-1080 Homo sapiens ED50 > 100.0 uM PMID[11277741]
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense IC50 = 2.8 ug.mL-1 PMID[12662093]
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense IC50 = 1.3 ug.mL-1 PMID[12662093]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 62.6 uM PMID[11277741]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 77.3 % PMID[9461664]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 100.0 % PMID[9461664]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 62.8 % PMID[9461664]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 = 2.6 ug.mL-1 PMID[12662093]

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 NPC70843 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
0.7647 Intermediate Similarity NPC90128
0.7111 Intermediate Similarity NPC123476
0.6604 Remote Similarity NPC84076
0.6458 Remote Similarity NPC88141
0.6304 Remote Similarity NPC130193
0.625 Remote Similarity NPC69332
0.6122 Remote Similarity NPC120693
0.566 Remote Similarity NPC23402
0.5577 Remote Similarity NPC285350
0.5577 Remote Similarity NPC95178
0.5472 Remote Similarity NPC8931
0.5472 Remote Similarity NPC277394
0.5455 Remote Similarity NPC188677
0.5349 Remote Similarity NPC260000
0.5273 Remote Similarity NPC19290
0.5263 Remote Similarity NPC189844
0.5208 Remote Similarity NPC29989
0.5208 Remote Similarity NPC52087
0.5111 Remote Similarity NPC68269

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC70843 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
NPD

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