Natural Product: NPC470213

Natural Product IDNPC470213
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-[(3R,5S)-3,5-Dihydroxy-7-(4-Hydroxyphenyl)Heptyl]-3-Methoxybenzene-1,2-Diol
IUPAC Name 5-[(3R,5S)-3,5-dihydroxy-7-(4-hydroxyphenyl)heptyl]-3-methoxybenzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1824569
PubChem CID 53387512
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 SCVDDDBKWRBFKH-DLBZAZTESA-N
Standard InCHI InChI=1S/C20H26O6/c1-26-19-11-14(10-18(24)20(19)25)5-9-17(23)12-16(22)8-4-13-2-6-15(21)7-3-13/h2-3,6-7,10-11,16-17,21-25H,4-5,8-9,12H2,1H3/t16-,17+/m0/s1
SMILES COc1cc(CC[C@H](C[C@H](CCc2ccc(cc2)O)O)O)cc(c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.17 Volume:   374.286
?
Van der Waals volume.
Dense:   0.968 LogP:   1.706
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.87
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.571
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   12.0
TPSA:   110.38
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.438 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.075 Fsp3:   0.4
MCE-18:   28.0
?
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:   1
Colloidal aggregators:   0.407 Fluc inhibitor:   0.254
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.018
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.11
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.555 Promiscuous compounds:   0.386

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.297 MDCK Permeability:   -4.961
Pgp-inhibitor:   0.035 Pgp-substrate:   0.978
PAMPA:   0.259
?
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%):   0.756 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.26
Plasma Protein Binding (PPB):   86.71% Volume Distribution (VD):   -0.225
Fu: 15.619%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.967 BCRP inhibitor:   0.965
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.326 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.98 CYP2C9-substrate:   0.016
CYP2D6-inhibitor:   0.946 CYP2D6-substrate:   0.066
CYP3A4-inhibitor:   0.312 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.782
HLM stability:   0.217
?
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):  12.516 Half-life (T1/2):  1.966

ADMET: Toxicity

hERG Blockers:  0.384 hERG Blockers (10um):  0.749
Human Hepatotoxicity (H-HT):  0.744 Drug-induced Liver Injury (DILI):  0.081
AMES Toxicity:  0.089 Rat Oral Acute Toxicity:  0.03
Maximum Recommended Daily Dose:  0.933 Skin Sensitization:  0.899
Carcinogencity:  0.158 Eye Corrosion:  0.009
Eye Irritation:  0.865 Respiratory Toxicity:  0.313
Drug-induced Neurotoxicity:  0.222 Ototoxicity:  0.836
Hematotoxicity:  0.073 Drug-induced Nephrotoxicity:  0.866
Genotoxicity:  0.036 RPMI-8226 Immunitoxicity:  0.03
A549 Cytotoxicity:  0.615 Hek293 Cytotoxicity:  0.515
BCF:   0.399
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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:   2.954
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.34
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.67
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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]
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]
NPO22741 Curcuma kwangsiensis 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]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 2410.0 nM PMID[25765759]

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 NPC470213 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
0.7447 Intermediate Similarity NPC186843
0.7292 Intermediate Similarity NPC473853
0.7292 Intermediate Similarity NPC470212
0.6667 Remote Similarity NPC343720
0.6667 Remote Similarity NPC54872
0.6522 Remote Similarity NPC179002
0.6522 Remote Similarity NPC257430
0.6458 Remote Similarity NPC312675
0.6458 Remote Similarity NPC262156
0.6458 Remote Similarity NPC184651
0.6458 Remote Similarity NPC113865
0.6279 Remote Similarity NPC91461
0.6279 Remote Similarity NPC7686
0.6279 Remote Similarity NPC40258
0.6182 Remote Similarity NPC310718
0.6154 Remote Similarity NPC324571
0.5962 Remote Similarity NPC98631
0.5962 Remote Similarity NPC206615
0.5818 Remote Similarity NPC311595
0.5818 Remote Similarity NPC24474
0.5745 Remote Similarity NPC213730
0.5652 Remote Similarity NPC187583
0.5517 Remote Similarity NPC215941
0.5517 Remote Similarity NPC123196
0.5517 Remote Similarity NPC311419
0.551 Remote Similarity NPC299028
0.5312 Remote Similarity NPC201587
0.5208 Remote Similarity NPC474272
0.5091 Remote Similarity NPC79383
0.5082 Remote Similarity NPC65935
0.5082 Remote Similarity NPC319282

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470213 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