Natural Product: NPC216468

Natural Product IDNPC216468
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R)-1,7-Bis(4-Hydroxyphenyl)-(6E)-6-Hepten-3-Ol
IUPAC Name 4-[(E,3R)-3-hydroxy-7-(4-hydroxyphenyl)hept-6-enyl]phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1269827
PubChem CID 38362130
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 HLWUXTFOZZSNLD-XKKXFUJGSA-N
Standard InCHI InChI=1S/C19H22O3/c20-17(10-7-16-8-13-19(22)14-9-16)4-2-1-3-15-5-11-18(21)12-6-15/h1,3,5-6,8-9,11-14,17,20-22H,2,4,7,10H2/b3-1+/t17-/m1/s1
SMILES O[C@@H](CCc1ccc(cc1)O)CC/C=C/c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.16 Volume:   327.983
?
Van der Waals volume.
Dense:   0.909 LogP:   3.399
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.51
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.728
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   13.0
TPSA:   60.69
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.727 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.619 Fsp3:   0.263
MCE-18:   22.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.641 Fluc inhibitor:   0.914
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.075
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.757 Promiscuous compounds:   0.411

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.052 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.486 Pgp-substrate:   0.064
PAMPA:   0.03
?
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):   0.0
20% Bioavailability (F20%):   0.874 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.019
Plasma Protein Binding (PPB):   89.077% Volume Distribution (VD):   -0.426
Fu: 7.843%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.762
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.408 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.566 CYP2C9-substrate:   0.739
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.624
CYP3A4-inhibitor:   0.203 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.819
?
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):  11.945 Half-life (T1/2):  1.12

ADMET: Toxicity

hERG Blockers:  0.647 hERG Blockers (10um):  0.867
Human Hepatotoxicity (H-HT):  0.845 Drug-induced Liver Injury (DILI):  0.026
AMES Toxicity:  0.159 Rat Oral Acute Toxicity:  0.019
Maximum Recommended Daily Dose:  0.955 Skin Sensitization:  0.943
Carcinogencity:  0.087 Eye Corrosion:  0.011
Eye Irritation:  0.905 Respiratory Toxicity:  0.402
Drug-induced Neurotoxicity:  0.427 Ototoxicity:  0.725
Hematotoxicity:  0.06 Drug-induced Nephrotoxicity:  0.782
Genotoxicity:  0.065 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.351 Hek293 Cytotoxicity:  0.851
BCF:   1.359
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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:   4.015
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.092
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.743
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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
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. rhizome n.a. DOI[10.1021/np100392m]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np100392m]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota rhizomes Kampaengsaen district, Nakhon Pathom province, Thailand n.a. PMID[18554915]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota aerial parts n.a. n.a. PMID[20196571]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[20879743]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[21807513]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[23910596]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8176399]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22901 Curcuma comosa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22901 Curcuma comosa 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
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition = 25.5 % PMID[23910596]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 = 16110.0 nM PMID[20879743]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 360.0 nM PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 90.5 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 79.3 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 67.3 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 47.5 % PMID[23910596]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 27.7 % PMID[23910596]

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 NPC216468 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
1.0 High Similarity NPC78119
0.881 High Similarity NPC51333
0.8605 High Similarity NPC147634
0.8605 High Similarity NPC79793
0.7255 Intermediate Similarity NPC207613
0.7021 Intermediate Similarity NPC55617
0.7021 Intermediate Similarity NPC62258
0.6977 Remote Similarity NPC164449
0.6977 Remote Similarity NPC184030
0.6122 Remote Similarity NPC285350
0.6042 Remote Similarity NPC120693
0.5909 Remote Similarity NPC132078
0.5909 Remote Similarity NPC600556
0.5854 Remote Similarity NPC91461
0.5854 Remote Similarity NPC7686
0.5854 Remote Similarity NPC40258
0.551 Remote Similarity NPC226401
0.551 Remote Similarity NPC174096
0.5435 Remote Similarity NPC179002
0.5435 Remote Similarity NPC257430
0.5385 Remote Similarity NPC8931
0.537 Remote Similarity NPC86900
0.5366 Remote Similarity NPC138117
0.5366 Remote Similarity NPC325292
0.5333 Remote Similarity NPC213730
0.5273 Remote Similarity NPC154899
0.5273 Remote Similarity NPC233396
0.525 Remote Similarity NPC239808
0.5208 Remote Similarity NPC177576
0.5088 Remote Similarity NPC135464
0.5088 Remote Similarity NPC92623

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC216468 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