Natural Product: NPC283088

Natural Product IDNPC283088
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1',4-Dihydroxy-1,6'-Dimethyl-6,7-Dihydro-2,2'-Binaphthyl-5,5',8,8'-Tetraone
IUPAC Name 5-hydroxy-6-(4-hydroxy-1-methyl-5,8-dioxo-6,7-dihydronaphthalen-2-yl)-2-methylnaphthalene-1,4-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1097168
PubChem CID 46888888
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 BILDVPLFDVMZBG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H16O6/c1-9-7-16(25)19-12(21(9)27)4-3-11(22(19)28)13-8-17(26)20-15(24)6-5-14(23)18(20)10(13)2/h3-4,7-8,26,28H,5-6H2,1-2H3
SMILES O=C1C(=CC(=O)c2c1ccc(c2O)c1cc(O)c2c(c1C)C(=O)CCC2=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.09 Volume:   378.583
?
Van der Waals volume.
Dense:   0.993 LogP:   3.346
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.78
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.195
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   26.0
TPSA:   108.74
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.788 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.996 Fsp3:   0.182
MCE-18:   56.0
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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:   0 PAINS Alert:   1
Colloidal aggregators:   0.629 Fluc inhibitor:   0.958
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.641
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.532
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.289 Promiscuous compounds:   0.294

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.897 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.042 Pgp-substrate:   0.0
PAMPA:   0.995
?
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):   0.041
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.024
50% Bioavailability (F50%):   0.602

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.998
Plasma Protein Binding (PPB):   98.009% Volume Distribution (VD):   -0.135
Fu: 1.775%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.882

ADMET: Metabolism

CYP1A2-inhibitor:   0.901 CYP1A2-substrate:   0.966
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.694
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.238
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.007
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.73
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.993
HLM stability:   0.941
?
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):  1.381 Half-life (T1/2):  1.337

ADMET: Toxicity

hERG Blockers:  0.079 hERG Blockers (10um):  0.474
Human Hepatotoxicity (H-HT):  0.905 Drug-induced Liver Injury (DILI):  0.985
AMES Toxicity:  0.946 Rat Oral Acute Toxicity:  0.79
Maximum Recommended Daily Dose:  0.915 Skin Sensitization:  0.975
Carcinogencity:  0.866 Eye Corrosion:  0.0
Eye Irritation:  0.959 Respiratory Toxicity:  0.981
Drug-induced Neurotoxicity:  0.551 Ototoxicity:  0.596
Hematotoxicity:  0.854 Drug-induced Nephrotoxicity:  0.743
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.434
A549 Cytotoxicity:  0.817 Hek293 Cytotoxicity:  0.877
BCF:   1.677
?
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:   4.822
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.897
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.48
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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
NPO22192 Cribraria cancellata Species Cribrariaceae Eukaryota n.a. n.a. n.a. PMID[14695806]
NPO20721 Halichondria panicea Species Halichondriidae Eukaryota n.a. n.a. n.a. PMID[20695474]
NPO22069 Persea major Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[2614421]
NPO20721 Halichondria panicea Species Halichondriidae Eukaryota n.a. n.a. n.a. PMID[27035556]
NPO23517 Heterotropa aspera n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO18387 Sedum formosanum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22196 Kickxia ramosissima Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20721 Halichondria panicea Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21383 Cnicothamnus lorentzii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23045 Lotus helleri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18256 Aconitum excelsum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23045 Lotus helleri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18256 Aconitum excelsum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23432 Viguiera oaxacana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9038 Aconitum burnatii Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13113 Ardisia kivuensis Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22999 Cussonia spicata Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22069 Persea major Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23045 Lotus helleri Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19736 Haplopappus glutinosus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23865 Scorzonera veratrifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23517 Heterotropa aspera n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO18387 Sedum formosanum Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18256 Aconitum excelsum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17645.1 Orobanche cernua var. cumana Varieties Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20094 Loranthus micranthus Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22831 Isodon angustifolius Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18921 Athrixia phylicoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21383 Cnicothamnus lorentzii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22192 Cribraria cancellata Species Cribrariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20721 Halichondria panicea Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22196 Kickxia ramosissima Species Plantaginaceae 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

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
- Aedes aegypti LC50 = 31.21 ug.mL-1 PMID[20347303]
- Aedes aegypti LC90 = 42.72 ug ml-1 PMID[20347303]

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 NPC283088 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
0.62 Remote Similarity NPC55949

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC283088 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