Natural Product: NPC166863

Natural Product IDNPC166863
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JIJQATZAZOPDCS-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5319632
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002507] Homoisoflavonoids
        • [CHEMONTID:0002508] Homoisoflavans

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 JIJQATZAZOPDCS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H18O6/c1-22-15-6-10(2-5-13(15)19)8-17(21)9-23-14-7-11(18)3-4-12(14)16(17)20/h2-7,16,18-21H,8-9H2,1H3
SMILES COc1cc(ccc1O)CC1(COc2cc(ccc2C1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   318.11 Volume:   313.841
?
Van der Waals volume.
Dense:   1.014 LogP:   0.654
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.999
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.736
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   17.0
TPSA:   99.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.684 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.389 Fsp3:   0.294
MCE-18:   62.182
?
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:   0.104 Fluc inhibitor:   0.231
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.045
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.12
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.174 Promiscuous compounds:   0.251

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.01 MDCK Permeability:   -4.776
Pgp-inhibitor:   0.0 Pgp-substrate:   0.881
PAMPA:   0.545
?
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):   0.01
20% Bioavailability (F20%):   0.836 30% Bioavailability (F30%):   0.796
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.72
Plasma Protein Binding (PPB):   70.996% Volume Distribution (VD):   0.087
Fu: 32.519%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.971
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.208
BSEP inhibitor:   0.174

ADMET: Metabolism

CYP1A2-inhibitor:   0.247 CYP1A2-substrate:   0.259
CYP2C19-inhibitor:   0.181 CYP2C19-substrate:   0.13
CYP2C9-inhibitor:   0.591 CYP2C9-substrate:   0.013
CYP2D6-inhibitor:   0.97 CYP2D6-substrate:   0.318
CYP3A4-inhibitor:   0.958 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.103
HLM stability:   0.656
?
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):  7.511 Half-life (T1/2):  2.352

ADMET: Toxicity

hERG Blockers:  0.125 hERG Blockers (10um):  0.396
Human Hepatotoxicity (H-HT):  0.474 Drug-induced Liver Injury (DILI):  0.094
AMES Toxicity:  0.438 Rat Oral Acute Toxicity:  0.232
Maximum Recommended Daily Dose:  0.467 Skin Sensitization:  0.417
Carcinogencity:  0.644 Eye Corrosion:  0.002
Eye Irritation:  0.837 Respiratory Toxicity:  0.685
Drug-induced Neurotoxicity:  0.223 Ototoxicity:  0.501
Hematotoxicity:  0.1 Drug-induced Nephrotoxicity:  0.275
Genotoxicity:  0.426 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.082 Hek293 Cytotoxicity:  0.451
BCF:   0.842
?
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:   2.996
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.883
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.437
?
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
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[1402962]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. PMID[15387653]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. heartwood n.a. PMID[19420770]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20815207]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. bark n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. heartwood n.a. PMID[21800859]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21800859]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[22207282]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. PMID[22325941]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23127886]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23234407]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[23806866]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. Konya, Turkey 2007-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota root bark University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic 2011-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota leaves Chungbuk, Korea n.a. PMID[25935644]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[25981820]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota seeds Nanning, Guangxi Province, China 2013-APR PMID[26398312]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Flower Buds n.a. n.a. PMID[26977531]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. latex n.a. PMID[27294120]
NPO28265 Morus alba Species Moraceae Eukaryota Root barks n.a. n.a. PMID[3097265]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[34770801]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[34964904]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[36529712]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36985392]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[37836118]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39684253]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39699537]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[8904847]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2554 Biancaea sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2654 Beaumontia grandiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2554 Biancaea sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2654 Beaumontia grandiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29935 Caesalpinia sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2554 Biancaea sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2654 Beaumontia grandiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23323 Dianthus superbus Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2554 Biancaea sappan Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3987 Syzygium aromaticum Species Myrtaceae 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

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 NPC166863 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
0.7037 Intermediate Similarity NPC164787
0.6167 Remote Similarity NPC67876
0.6066 Remote Similarity NPC230734
0.5645 Remote Similarity NPC211758
0.5312 Remote Similarity NPC87794
0.5094 Remote Similarity NPC255675

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC166863 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