Natural Product: NPC86030

Natural Product IDNPC86030
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Rel-(7Alpha,8Beta)-3-Methoxy-4',7-Epoxy-8,3'-Oxyneolignan-4,9,9'-Triol
IUPAC Name 4-[(2R,3R)-3-(hydroxymethyl)-6-(3-hydroxypropyl)-2,3-dihydro-1,4-benzodioxin-2-yl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3088128
PubChem CID 76317135
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002699] Benzodioxanes
        • [CHEMONTID:0002704] Phenylbenzodioxanes
          • [CHEMONTID:0002707] Phenylbenzo-1,4-dioxanes

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 CYLVTAFKOSKXKE-RTBURBONSA-N
Standard InCHI InChI=1S/C19H22O6/c1-23-16-10-13(5-6-14(16)22)19-18(11-21)24-17-9-12(3-2-8-20)4-7-15(17)25-19/h4-7,9-10,18-22H,2-3,8,11H2,1H3/t18-,19-/m1/s1
SMILES COc1cc(ccc1O)[C@@H]1[C@@H](CO)Oc2cc(CCCO)ccc2O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.14 Volume:   348.433
?
Van der Waals volume.
Dense:   0.993 LogP:   2.172
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.332
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.503
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   88.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.743 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.104 Fsp3:   0.368
MCE-18:   53.615
?
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:   0.535 Fluc inhibitor:   0.788
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.197
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.115 Promiscuous compounds:   0.283

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.164 MDCK Permeability:   -4.762
Pgp-inhibitor:   0.898 Pgp-substrate:   0.403
PAMPA:   0.067
?
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):   0.009
20% Bioavailability (F20%):   0.126 30% Bioavailability (F30%):   0.412
50% Bioavailability (F50%):   0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.066 MRP1:   0.686
Plasma Protein Binding (PPB):   86.013% Volume Distribution (VD):   -0.212
Fu: 14.754%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.968 BCRP inhibitor:   0.681
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.896 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.523 CYP2D6-substrate:   0.272
CYP3A4-inhibitor:   0.918 CYP3A4-substrate:   0.003
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.792
HLM stability:   0.001
?
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):  6.938 Half-life (T1/2):  1.509

ADMET: Toxicity

hERG Blockers:  0.175 hERG Blockers (10um):  0.327
Human Hepatotoxicity (H-HT):  0.799 Drug-induced Liver Injury (DILI):  0.366
AMES Toxicity:  0.682 Rat Oral Acute Toxicity:  0.073
Maximum Recommended Daily Dose:  0.045 Skin Sensitization:  0.977
Carcinogencity:  0.517 Eye Corrosion:  0.027
Eye Irritation:  0.959 Respiratory Toxicity:  0.195
Drug-induced Neurotoxicity:  0.404 Ototoxicity:  0.752
Hematotoxicity:  0.329 Drug-induced Nephrotoxicity:  0.729
Genotoxicity:  0.05 RPMI-8226 Immunitoxicity:  0.062
A549 Cytotoxicity:  0.335 Hek293 Cytotoxicity:  0.376
BCF:   0.576
?
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:   3.036
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.55
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.689
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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
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. leaf n.a. PMID[11348221]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[15844957]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits n.a. n.a. PMID[16378361]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota fruits Tahiti n.a. PMID[17378609]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[17480098]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota roots n.a. n.a. PMID[18076142]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[24224843]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[27196335]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[32083868]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[36014413]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4323 Morinda citrifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4323 Morinda citrifolia Species Rubiaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 > 30000.0 nM PMID[19845338]

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

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 NPC86030 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
0.9434 High Similarity NPC5851
0.7627 Intermediate Similarity NPC605857
0.6562 Remote Similarity NPC481838
0.6393 Remote Similarity NPC194519
0.6269 Remote Similarity NPC126206
0.619 Remote Similarity NPC111247
0.619 Remote Similarity NPC292056
0.597 Remote Similarity NPC98809
0.5821 Remote Similarity NPC476394
0.5811 Remote Similarity NPC138688
0.5811 Remote Similarity NPC72787
0.5811 Remote Similarity NPC217795
0.5811 Remote Similarity NPC58223
0.5672 Remote Similarity NPC224876
0.5641 Remote Similarity NPC470935
0.5467 Remote Similarity NPC36916
0.5467 Remote Similarity NPC36
0.5467 Remote Similarity NPC7154
0.5467 Remote Similarity NPC125039
0.5467 Remote Similarity NPC7688
0.5373 Remote Similarity NPC29799
0.5373 Remote Similarity NPC263367
0.5373 Remote Similarity NPC54743
0.5231 Remote Similarity NPC293701
0.5224 Remote Similarity NPC163332
0.5167 Remote Similarity NPC71090
0.5161 Remote Similarity NPC479112
0.5152 Remote Similarity NPC16208
0.5067 Remote Similarity NPC476347

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC86030 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
0.5467 Remote Similarity NPD6166 Phase 2
0.5467 Remote Similarity NPD6167 Clinical (unspecified phase)
0.5467 Remote Similarity NPD6168 Clinical (unspecified phase)

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