Natural Product: NPC474770

Natural Product IDNPC474770
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bicyclol
IUPAC Name methyl 4-[5-(hydroxymethyl)-7-methoxy-1,3-benzodioxol-4-yl]-7-methoxy-1,3-benzodioxole-5-carboxylate
Synonyms Bicyclol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL482035
PubChem CID 9821754
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000238] Tannins
        • [CHEMONTID:0001710] Hydrolyzable tannins

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 KXMTXZACPVCDMH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O9/c1-22-11-4-9(6-20)13(17-15(11)25-7-27-17)14-10(19(21)24-3)5-12(23-2)16-18(14)28-8-26-16/h4-5,20H,6-8H2,1-3H3
SMILES COc1cc(CO)c(c2c(cc(c3c2OCO3)OC)C(=O)OC)c2c1OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.1 Volume:   363.611
?
Van der Waals volume.
Dense:   1.073 LogP:   2.056
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.518
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.723
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   21.0
TPSA:   101.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.769 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.869 Fsp3:   0.316
MCE-18:   49.68
?
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:   0
Colloidal aggregators:   0.138 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.585
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.144
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.094 Promiscuous compounds:   0.481

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.815 MDCK Permeability:   -4.706
Pgp-inhibitor:   0.741 Pgp-substrate:   0.039
PAMPA:   0.042
?
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):   0.006
20% Bioavailability (F20%):   0.052 30% Bioavailability (F30%):   0.024
50% Bioavailability (F50%):   0.222

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.186 MRP1:   0.985
Plasma Protein Binding (PPB):   77.697% Volume Distribution (VD):   0.055
Fu: 25.115%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.941
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.109
BSEP inhibitor:   0.976

ADMET: Metabolism

CYP1A2-inhibitor:   0.985 CYP1A2-substrate:   0.865
CYP2C19-inhibitor:   0.981 CYP2C19-substrate:   0.012
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.951
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.99
CYP3A4-inhibitor:   0.256 CYP3A4-substrate:   0.169
CYP2B6-substrate:   0.086 CYP2C8-inhibitor:   0.105
HLM stability:   0.454
?
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):  3.53 Half-life (T1/2):  1.066

ADMET: Toxicity

hERG Blockers:  0.111 hERG Blockers (10um):  0.482
Human Hepatotoxicity (H-HT):  0.463 Drug-induced Liver Injury (DILI):  0.744
AMES Toxicity:  0.391 Rat Oral Acute Toxicity:  0.147
Maximum Recommended Daily Dose:  0.582 Skin Sensitization:  0.435
Carcinogencity:  0.857 Eye Corrosion:  0.001
Eye Irritation:  0.633 Respiratory Toxicity:  0.354
Drug-induced Neurotoxicity:  0.505 Ototoxicity:  0.48
Hematotoxicity:  0.323 Drug-induced Nephrotoxicity:  0.374
Genotoxicity:  0.365 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.047 Hek293 Cytotoxicity:  0.288
BCF:   1.06
?
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:   3.318
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.729
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.929
?
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
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10654410]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[10843587]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[11678654]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[15568770]
NPO11713 Hypericum scabrum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[15568778]
NPO11713 Hypericum scabrum Species Hypericaceae Eukaryota n.a. Uzbekistan n.a. PMID[15568778]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15787451]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[16124785]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. leaf n.a. PMID[16235962]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. stem n.a. PMID[16235962]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16392664]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. stem n.a. PMID[16394567]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. root n.a. PMID[16394567]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota roots Hualien Hsien, Taiwan 2003-JUL PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[17951038]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[17970593]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18175961]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. rhizome n.a. PMID[18787781]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. aerial part n.a. PMID[18991207]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota essential oil Tibet n.a. PMID[20944522]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[21302967]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota Roots Anhui, China n.a. PMID[22694318]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24295087]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24738739]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[25612070]
NPO40316 Rehmannia chingii Species Orobanchaceae Eukaryota n.a. n.a. n.a. PMID[26859776]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[27228227]
NPO11713 Hypericum scabrum Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[27280968]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27575476]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota Twigs n.a. n.a. PMID[28541690]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[29595972]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[30298740]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[30379546]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31050424]
NPO2519 Tinospora baenzigeri Species Menispermaceae Eukaryota Stems n.a. n.a. PMID[31135149]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[31556297]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[31596079]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[31994661]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[32035880]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[32674448]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[34500567]
NPO56910 Eugenia gracillima Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36442761]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[36552598]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[36770639]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37533252]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[37746728]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38998569]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39013008]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39395223]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[39489989]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[4207788]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[4629903]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[7528269]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[9544564]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[9868163]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. Database[Article]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. stem n.a. Database[Article]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11713 Hypericum scabrum Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2519 Tinospora baenzigeri Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2519 Tinospora baenzigeri Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14089 Hypericum ascyron Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6701 Cinnamomum camphora Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23756 Aspergillus flavus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16087 Atractylodes lancea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29110 Litsea cubeba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2519 Tinospora baenzigeri Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11713 Hypericum scabrum Species Hypericaceae 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
NPO56910 Eugenia gracillima Oil n.a. 4.89 n.a. n.a. % PMID[36442761]
NPO6701 Cinnamomum camphora Oil Leaves 0.70 n.a. n.a. % PMID[31994661]

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
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 5.868 % DOI[10.6019/CHEMBL4495564]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = -14.92 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = -0.94 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Inhibition = 28.28 % PMID[28958618]
NPT65 Cell line HepG2 Homo sapiens Activity = 34.8 % PMID[28541690]
NPT65 Cell line HepG2 Homo sapiens Inhibition = 52.6 % PMID[30379546]
NPT65 Cell line HepG2 Homo sapiens Inhibition = 15.7 % PMID[31135149]
NPT65 Cell line HepG2 Homo sapiens Activity = 49.0 % PMID[31556297]
NPT65 Cell line HepG2 Homo sapiens Activity = 32.0 % PMID[33606538]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 8.5 % DOI[10.21203/rs.3.rs-23951/v1]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -0.19 % DOI[10.6019/CHEMBL4495565]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 27.4 % PMID[16643038]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 11.2 % PMID[20092289]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 47.0 % PMID[19916529]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 67.0 % PMID[21627109]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 42.0 % PMID[22694318]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 16.7 % PMID[22916954]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 42.5 % PMID[24195447]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 29.4 % PMID[24295087]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 19.5 % PMID[27280968]
NPT21742 Cell line L02 Homo sapiens Activity = 47.0 % PMID[33606538]
NPT21742 Cell line L02 Homo sapiens Activity = 26.2 % PMID[29353722]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Survival = 66.5 % PMID[21090801]
NPT65 Cell line HepG2 Homo sapiens Survival = 52.87 % PMID[27228227]
NPT65 Cell line HepG2 Homo sapiens Survival = 49.0 % PMID[29595972]
NPT65 Cell line HepG2 Homo sapiens Survival = 31.9 % PMID[31050424]
NPT65 Cell line HepG2 Homo sapiens Survival = 60.0 % PMID[38600636]
NPT21742 Cell line L02 Homo sapiens Survival = 63.6 % PMID[22916954]
NPT21742 Cell line L02 Homo sapiens Survival = 76.0 % PMID[24195447]
NPT21742 Cell line L02 Homo sapiens Survival = 62.5 % PMID[24295087]
NPT2 Others Unspecified n.a. Survival = 80.0 % PMID[20192242]





 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 NPC474770 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
0.5614 Remote Similarity NPC304821

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474770 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