Natural Product: NPC73535

Natural Product IDNPC73535
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4''-Deoxy-3-Hydroxyterphenyllin
IUPAC Name 4-(2-hydroxy-3,6-dimethoxy-4-phenylphenyl)benzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1795347
PubChem CID 53262867
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0002042] Terphenyls
          • [CHEMONTID:0002126] P-terphenyls

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 QVPSTGJFYRHFSU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O5/c1-24-17-11-14(12-6-4-3-5-7-12)20(25-2)19(23)18(17)13-8-9-15(21)16(22)10-13/h3-11,21-23H,1-2H3
SMILES COc1cc(c2ccccc2)c(c(c1c1ccc(c(c1)O)O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.12 Volume:   349.03
?
Van der Waals volume.
Dense:   0.969 LogP:   3.25
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.888
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   79.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.623 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.172 Fsp3:   0.1
MCE-18:   18.0
?
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:   0.841 Fluc inhibitor:   0.231
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.541
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.695
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.562 Promiscuous compounds:   0.536

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.022 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.002 Pgp-substrate:   0.013
PAMPA:   0.888
?
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):   0.049
20% Bioavailability (F20%):   0.291 30% Bioavailability (F30%):   0.171
50% Bioavailability (F50%):   0.86

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.934
Plasma Protein Binding (PPB):   98.989% Volume Distribution (VD):   -0.364
Fu: 0.964%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.835
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.189
BSEP inhibitor:   0.238

ADMET: Metabolism

CYP1A2-inhibitor:   0.957 CYP1A2-substrate:   0.929
CYP2C19-inhibitor:   0.76 CYP2C19-substrate:   0.517
CYP2C9-inhibitor:   0.948 CYP2C9-substrate:   0.044
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.992
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.641
CYP2B6-substrate:   0.013 CYP2C8-inhibitor:   0.411
HLM stability:   0.946
?
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):  11.302 Half-life (T1/2):  1.311

ADMET: Toxicity

hERG Blockers:  0.186 hERG Blockers (10um):  0.763
Human Hepatotoxicity (H-HT):  0.532 Drug-induced Liver Injury (DILI):  0.5
AMES Toxicity:  0.428 Rat Oral Acute Toxicity:  0.403
Maximum Recommended Daily Dose:  0.627 Skin Sensitization:  0.934
Carcinogencity:  0.437 Eye Corrosion:  0.034
Eye Irritation:  0.945 Respiratory Toxicity:  0.627
Drug-induced Neurotoxicity:  0.283 Ototoxicity:  0.535
Hematotoxicity:  0.142 Drug-induced Nephrotoxicity:  0.157
Genotoxicity:  0.395 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.771 Hek293 Cytotoxicity:  0.466
BCF:   1.311
?
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:   4.274
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.304
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.79
?
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
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota rhizosphere Sonoran desert n.a. PMID[15620238]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17542490]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17564467]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19053517]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21366228]
NPO9892 Aspergillus taichungensis Species Aspergillaceae Eukaryota isolated from the root soil of the mangrove plant Acrostichum aureum n.a. n.a. PMID[21486068]
NPO9892 Aspergillus taichungensis Species Aspergillaceae Eukaryota a root soil fungus isolated from the mangrove plant Acrostichum aureum n.a. n.a. PMID[21486068]
NPO9892 Aspergillus taichungensis Species Aspergillaceae Eukaryota n.a. mycelium n.a. PMID[21486068]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21718031]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21854017]
NPO13765 Acrostichum aureum Species Pteridaceae Eukaryota n.a. aerial part n.a. PMID[21899268]
NPO33649 Aspergillus sp. YXf3 Species Aspergillaceae Eukaryota isolated from a healthy leaf of Ginkgo biloba the campus of Nanjing University, Nanjing, China 2008-OCT PMID[22196792]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota healthy leaf of Ginkgo biloba campus of Nanjing University, Nanjing, China 2008-OCT PMID[22196792]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota isolated from the sponge Xestospongia testudinaria n.a. n.a. PMID[22225637]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota Isolated from a sandy-loam soil sample 50 m inland from Waikiki Beach, Honolulu, Hawaii 2010-JUL PMID[22400916]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22703109]
NPO13765 Acrostichum aureum Species Pteridaceae Eukaryota n.a. aerial part n.a. PMID[22906240]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23527875]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24050204]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25001296]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25581396]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26273902]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31012585]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[33305943]
NPO13272 Ulva lactuca Species Ulvaceae Eukaryota n.a. n.a. n.a. PMID[39769283]
NPO33649 Aspergillus sp. YXf3 Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9892 Aspergillus taichungensis Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12872 Taraxacum disseminatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11049 Solanum capsicastrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12686 Sideritis hirsuta Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14461 Vibrio fluvialis Species Vibrionaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO13272 Ulva lactuca Species Ulvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11049 Solanum capsicastrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13272 Ulva lactuca Species Ulvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11049 Solanum capsicastrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13272 Ulva lactuca Species Ulvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13272 Ulva lactuca Species Ulvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11049 Solanum capsicastrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22797 Fleroya stipulosa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9892 Aspergillus taichungensis Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13272 Ulva lactuca Species Ulvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7010 Anthocleista procera Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14461 Vibrio fluvialis Species Vibrionaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO13868 Gnaphalium oligandrum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11049 Solanum capsicastrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10556 Eria jarensis Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11828 Mucor hiemalis Species Mucoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14357 Ixeris denticulata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26896 Wulfenia orientalis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13765 Acrostichum aureum Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12686 Sideritis hirsuta Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12872 Taraxacum disseminatum Species Asteraceae 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
NPT116 Cell line HL-60 Homo sapiens IC50 = 9890.0 nM PMID[21486068]
NPT168 Cell line P388 Mus musculus IC50 = 2700.0 nM PMID[21486068]
NPT81 Cell line A549 Homo sapiens IC50 = 40710.0 nM PMID[21486068]
NPT2 Others Unspecified n.a. IC50 > 30000.0 nM PMID[22196792]

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 NPC73535 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
0.85 High Similarity NPC272157
0.8462 Intermediate Similarity NPC201145
0.8049 Intermediate Similarity NPC25111
0.7073 Intermediate Similarity NPC90615
0.6 Remote Similarity NPC34431
0.5893 Remote Similarity NPC485410
0.5714 Remote Similarity NPC165026
0.5439 Remote Similarity NPC485408
0.5439 Remote Similarity NPC485411
0.5254 Remote Similarity NPC485407
0.5208 Remote Similarity NPC114155
0.5106 Remote Similarity NPC6262
0.5088 Remote Similarity NPC295719

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC73535 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