Natural Product: NPC471693

Natural Product IDNPC471693
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+)-Dihydroguaiaretic Acid
IUPAC Name (2S,3S)-1,4-bis(4-hydroxy-3-methoxyphenyl)butane-2,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3104944
PubChem CID 76324774
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 OEQIZINHSBTLBQ-HOTGVXAUSA-N
Standard InCHI InChI=1S/C18H22O6/c1-23-17-9-11(3-5-13(17)19)7-15(21)16(22)8-12-4-6-14(20)18(10-12)24-2/h3-6,9-10,15-16,19-22H,7-8H2,1-2H3/t15-,16-/m0/s1
SMILES COC1=C(C=CC(=C1)CC(C(CC2=CC(=C(C=C2)O)OC)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   334.14 Volume:   339.694
?
Van der Waals volume.
Dense:   0.984 LogP:   1.092
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.511
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.172
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 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:   0.614 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.937 Fsp3:   0.333
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:   0.29 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.01
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.309
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.347 Promiscuous compounds:   0.549

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.177 MDCK Permeability:   -4.8
Pgp-inhibitor:   0.001 Pgp-substrate:   0.791
PAMPA:   0.123
?
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):   0.047
20% Bioavailability (F20%):   0.526 30% Bioavailability (F30%):   0.636
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.626
Plasma Protein Binding (PPB):   55.509% Volume Distribution (VD):   -0.05
Fu: 42.329%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.529
BSEP inhibitor:   0.613

ADMET: Metabolism

CYP1A2-inhibitor:   0.077 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.822 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.975 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.978 CYP2D6-substrate:   0.049
CYP3A4-inhibitor:   0.713 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.711
HLM stability:   0.199
?
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):  10.061 Half-life (T1/2):  1.752

ADMET: Toxicity

hERG Blockers:  0.211 hERG Blockers (10um):  0.804
Human Hepatotoxicity (H-HT):  0.443 Drug-induced Liver Injury (DILI):  0.025
AMES Toxicity:  0.216 Rat Oral Acute Toxicity:  0.063
Maximum Recommended Daily Dose:  0.363 Skin Sensitization:  0.099
Carcinogencity:  0.083 Eye Corrosion:  0.0
Eye Irritation:  0.487 Respiratory Toxicity:  0.188
Drug-induced Neurotoxicity:  0.125 Ototoxicity:  0.88
Hematotoxicity:  0.04 Drug-induced Nephrotoxicity:  0.119
Genotoxicity:  0.018 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.212 Hek293 Cytotoxicity:  0.496
BCF:   0.697
?
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:   3.08
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.999
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.507
?
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
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[10924192]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[11754613]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. root n.a. PMID[14750033]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[15482936]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota roots n.a. n.a. PMID[18841903]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Roots n.a. n.a. PMID[24359277]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Aerial Parts n.a. n.a. PMID[24387347]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[31642320]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20323 Saururus chinensis Species Saururaceae 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
NPT20967 Cell line Platelet n.a. Activity = 74.5 % PMID[24387347]

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 NPC471693 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
0.8 Intermediate Similarity NPC255675
0.7143 Intermediate Similarity NPC257124
0.7059 Intermediate Similarity NPC156840
0.6944 Remote Similarity NPC221049
0.6486 Remote Similarity NPC8547
0.6486 Remote Similarity NPC140359
0.641 Remote Similarity NPC85488
0.6341 Remote Similarity NPC312675
0.6341 Remote Similarity NPC262156
0.6341 Remote Similarity NPC184651
0.6341 Remote Similarity NPC113865
0.6316 Remote Similarity NPC165133
0.6316 Remote Similarity NPC242885
0.6316 Remote Similarity NPC95614
0.6316 Remote Similarity NPC193544
0.6316 Remote Similarity NPC232316
0.625 Remote Similarity NPC197757
0.6042 Remote Similarity NPC310718
0.6 Remote Similarity NPC57490
0.6 Remote Similarity NPC603326
0.6 Remote Similarity NPC603989
0.5952 Remote Similarity NPC203133
0.587 Remote Similarity NPC343720
0.587 Remote Similarity NPC54872
0.5854 Remote Similarity NPC17943
0.5854 Remote Similarity NPC299406
0.5814 Remote Similarity NPC117214
0.5814 Remote Similarity NPC56214
0.5814 Remote Similarity NPC487676
0.5814 Remote Similarity NPC476968
0.5778 Remote Similarity NPC473853
0.5778 Remote Similarity NPC98631
0.5778 Remote Similarity NPC206615
0.5778 Remote Similarity NPC470212
0.5778 Remote Similarity NPC481914
0.5714 Remote Similarity NPC7097
0.5676 Remote Similarity NPC293619
0.5652 Remote Similarity NPC324571
0.5581 Remote Similarity NPC194416
0.5581 Remote Similarity NPC31344
0.5581 Remote Similarity NPC177291
0.5581 Remote Similarity NPC317769
0.5581 Remote Similarity NPC127937
0.5556 Remote Similarity NPC127587
0.5532 Remote Similarity NPC164386
0.55 Remote Similarity NPC181969
0.5455 Remote Similarity NPC66518
0.5435 Remote Similarity NPC5428
0.5435 Remote Similarity NPC607444
0.5417 Remote Similarity NPC137427
0.5333 Remote Similarity NPC51840
0.5333 Remote Similarity NPC227217
0.5333 Remote Similarity NPC117780
0.5333 Remote Similarity NPC82679
0.5319 Remote Similarity NPC311680
0.5319 Remote Similarity NPC212015
0.5306 Remote Similarity NPC311595
0.5306 Remote Similarity NPC481913
0.5306 Remote Similarity NPC24474
0.5263 Remote Similarity NPC246358
0.5263 Remote Similarity NPC203719
0.525 Remote Similarity NPC320987
0.5238 Remote Similarity NPC35071
0.5238 Remote Similarity NPC177475
0.5238 Remote Similarity NPC148615
0.5217 Remote Similarity NPC78974
0.5208 Remote Similarity NPC472090
0.5208 Remote Similarity NPC303680
0.5128 Remote Similarity NPC32163
0.5128 Remote Similarity NPC309203
0.5128 Remote Similarity NPC604189
0.5122 Remote Similarity NPC326599
0.5122 Remote Similarity NPC139519
0.5122 Remote Similarity NPC329595
0.5116 Remote Similarity NPC129889
0.5116 Remote Similarity NPC307006
0.5116 Remote Similarity NPC325625
0.5106 Remote Similarity NPC5018
0.5106 Remote Similarity NPC74817
0.5102 Remote Similarity NPC173308
0.5102 Remote Similarity NPC181079
0.5094 Remote Similarity NPC65935
0.5094 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 NPC471693 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
0.7143 Intermediate 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