Natural Product: NPC184651

Natural Product IDNPC184651
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R,5R)-1,7-Bis(4-Hydroxy-3-Methoxyphenyl)Heptane-3,5-Diol
IUPAC Name (3R,5R)-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL514825
PubChem CID 10883331
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 OELMAFBLFOKZJD-IAGOWNOFSA-N
Standard InCHI InChI=1S/C21H28O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h5-6,9-12,16-17,22-25H,3-4,7-8,13H2,1-2H3/t16-,17-/m1/s1
SMILES COc1cc(CC[C@H](C[C@@H](CCc2ccc(c(c2)OC)O)O)O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.19 Volume:   391.582
?
Van der Waals volume.
Dense:   0.961 LogP:   1.699
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.951
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.526
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   12.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.509 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.978 Fsp3:   0.429
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:   0
Colloidal aggregators:   0.424 Fluc inhibitor:   0.014
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.071
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.527 Promiscuous compounds:   0.524

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.115 MDCK Permeability:   -4.855
Pgp-inhibitor:   0.319 Pgp-substrate:   0.949
PAMPA:   0.012
?
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):   0.002
20% Bioavailability (F20%):   0.548 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.322
Plasma Protein Binding (PPB):   84.034% Volume Distribution (VD):   -0.223
Fu: 17.406%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.863
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.043
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.028
CYP2D6-inhibitor:   0.944 CYP2D6-substrate:   0.099
CYP3A4-inhibitor:   0.964 CYP3A4-substrate:   0.375
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.436
?
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):  9.423 Half-life (T1/2):  1.721

ADMET: Toxicity

hERG Blockers:  0.504 hERG Blockers (10um):  0.797
Human Hepatotoxicity (H-HT):  0.747 Drug-induced Liver Injury (DILI):  0.121
AMES Toxicity:  0.3 Rat Oral Acute Toxicity:  0.126
Maximum Recommended Daily Dose:  0.935 Skin Sensitization:  0.954
Carcinogencity:  0.248 Eye Corrosion:  0.003
Eye Irritation:  0.55 Respiratory Toxicity:  0.852
Drug-induced Neurotoxicity:  0.495 Ototoxicity:  0.835
Hematotoxicity:  0.529 Drug-induced Nephrotoxicity:  0.97
Genotoxicity:  0.033 RPMI-8226 Immunitoxicity:  0.156
A549 Cytotoxicity:  0.925 Hek293 Cytotoxicity:  0.793
BCF:   0.587
?
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:   3.112
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.272
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.602
?
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
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota rhizomes SiMao City, Yunnan Province, China 1996-OCT PMID[11908966]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota Rhizomes n.a. n.a. PMID[12350150]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota aerial parts n.a. n.a. PMID[16124773]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[18177011]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[19271742]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[20590154]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. PMID[20715765]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[32872604]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. PMID[33253561]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[36352904]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39679248]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[39680258]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[8064299]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[8064299]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Resin, Exudate, Sap n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO13332 Tacca chantrieri Species Taccaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20553 Zingiber officinale Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13332 Tacca chantrieri Species Taccaceae 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
NPT324 Individual protein Cyclooxygenase-1 Ovis aries IC50 > 100.0 ug.mL-1 PMID[19303782]
NPT325 Individual protein Cyclooxygenase-2 Ovis aries IC50 > 100.0 ug.mL-1 PMID[19303782]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT116 Cell line HL-60 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[11908966]
NPT34 Cell line BV-2 Mus musculus Activity = 84.3 % PMID[33253561]
NPT34 Cell line BV-2 Mus musculus Activity = 101.2 % PMID[33253561]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 48.7 ug.mL-1 PMID[19303782]
NPT1 Others Radical scavenging activity n.a. IC50 = 12.3 ug.mL-1 PMID[19303782]

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 NPC184651 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 NPC312675
1.0 High Similarity NPC262156
1.0 High Similarity NPC113865
0.9 High Similarity NPC473853
0.9 High Similarity NPC98631
0.9 High Similarity NPC206615
0.9 High Similarity NPC470212
0.878 High Similarity NPC324571
0.8571 High Similarity NPC343720
0.8571 High Similarity NPC54872
0.8182 Intermediate Similarity NPC311595
0.8182 Intermediate Similarity NPC24474
0.7447 Intermediate Similarity NPC310718
0.7333 Intermediate Similarity NPC164386
0.7174 Intermediate Similarity NPC137427
0.7045 Intermediate Similarity NPC186843
0.6923 Remote Similarity NPC8547
0.66 Remote Similarity NPC215941
0.66 Remote Similarity NPC123196
0.66 Remote Similarity NPC311419
0.6522 Remote Similarity NPC481914
0.6471 Remote Similarity NPC275724
0.6471 Remote Similarity NPC244246
0.6471 Remote Similarity NPC611247
0.6458 Remote Similarity NPC470213
0.6346 Remote Similarity NPC65935
0.6346 Remote Similarity NPC319282
0.6341 Remote Similarity NPC471693
0.6279 Remote Similarity NPC17943
0.6279 Remote Similarity NPC299406
0.625 Remote Similarity NPC485986
0.6226 Remote Similarity NPC207613
0.619 Remote Similarity NPC255675
0.6154 Remote Similarity NPC156840
0.6098 Remote Similarity NPC221049
0.6047 Remote Similarity NPC474320
0.6 Remote Similarity NPC481913
0.6 Remote Similarity NPC177291
0.6 Remote Similarity NPC127937
0.5854 Remote Similarity NPC257124
0.575 Remote Similarity NPC91461
0.575 Remote Similarity NPC7686
0.575 Remote Similarity NPC40258
0.5745 Remote Similarity NPC51840
0.5745 Remote Similarity NPC82679
0.5714 Remote Similarity NPC212015
0.5714 Remote Similarity NPC140359
0.5714 Remote Similarity NPC474272
0.5682 Remote Similarity NPC85488
0.566 Remote Similarity NPC20287
0.566 Remote Similarity NPC20404
0.5652 Remote Similarity NPC474214
0.56 Remote Similarity NPC303680
0.5581 Remote Similarity NPC165133
0.5581 Remote Similarity NPC242885
0.5581 Remote Similarity NPC95614
0.5581 Remote Similarity NPC193544
0.5581 Remote Similarity NPC232316
0.5556 Remote Similarity NPC12022
0.5556 Remote Similarity NPC278308
0.551 Remote Similarity NPC5018
0.551 Remote Similarity NPC74817
0.5476 Remote Similarity NPC187583
0.541 Remote Similarity NPC52277
0.54 Remote Similarity NPC311680
0.54 Remote Similarity NPC114298
0.54 Remote Similarity NPC159968
0.54 Remote Similarity NPC53305
0.54 Remote Similarity NPC606450
0.5357 Remote Similarity NPC252307
0.5357 Remote Similarity NPC245826
0.5333 Remote Similarity NPC57490
0.5333 Remote Similarity NPC603326
0.5333 Remote Similarity NPC603989
0.5294 Remote Similarity NPC282000
0.5294 Remote Similarity NPC4181
0.5294 Remote Similarity NPC201777
0.5294 Remote Similarity NPC604524
0.5227 Remote Similarity NPC213730
0.5217 Remote Similarity NPC197757
0.5208 Remote Similarity NPC117214
0.5208 Remote Similarity NPC66518
0.5208 Remote Similarity NPC487676
0.5208 Remote Similarity NPC476968
0.5192 Remote Similarity NPC487210
0.5094 Remote Similarity NPC123228
0.5094 Remote Similarity NPC123722
0.5094 Remote Similarity NPC164778
0.5094 Remote Similarity NPC163083
0.5077 Remote Similarity NPC199459

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC184651 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
0.5854 Remote Similarity NPD228 Phase 0

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