Natural Product: NPC54179

Natural Product IDNPC54179
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Helioxanthin
IUPAC Name 10-(1,3-benzodioxol-5-yl)-9H-[2]benzofuro[6,5-g][1,3]benzodioxol-7-one
Synonyms Helioxanthin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL436474
PubChem CID 177023
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001610] Arylnaphthalene lignans

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 JUBRYHUFFFYTGR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H12O6/c21-20-12-5-10-2-4-15-19(26-9-24-15)18(10)17(13(12)7-22-20)11-1-3-14-16(6-11)25-8-23-14/h1-6H,7-9H2
SMILES c1cc2c(cc1c1c3COC(=O)c3cc3ccc4c(c13)OCO4)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.06 Volume:   332.151
?
Van der Waals volume.
Dense:   1.048 LogP:   3.246
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.943
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.424
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   30.0
TPSA:   63.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   6.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.626 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.697 Fsp3:   0.15
MCE-18:   65.565
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.918 Fluc inhibitor:   0.366
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.86
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.482
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.32 Promiscuous compounds:   0.357

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.96 MDCK Permeability:   -4.677
Pgp-inhibitor:   0.357 Pgp-substrate:   0.002
PAMPA:   0.393
?
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):   0.0
20% Bioavailability (F20%):   0.014 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.117

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.99 MRP1:   0.77
Plasma Protein Binding (PPB):   97.335% Volume Distribution (VD):   0.131
Fu: 3.625%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.729
OATP1B3 inhibitor:   0.872 BCRP inhibitor:   0.012
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.987
CYP2C19-inhibitor:   0.975 CYP2C19-substrate:   0.848
CYP2C9-inhibitor:   0.972 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.785 CYP2C8-inhibitor:   0.0
HLM stability:   0.759
?
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):  2.301 Half-life (T1/2):  0.847

ADMET: Toxicity

hERG Blockers:  0.231 hERG Blockers (10um):  0.582
Human Hepatotoxicity (H-HT):  0.89 Drug-induced Liver Injury (DILI):  0.989
AMES Toxicity:  0.956 Rat Oral Acute Toxicity:  0.679
Maximum Recommended Daily Dose:  0.939 Skin Sensitization:  0.983
Carcinogencity:  0.994 Eye Corrosion:  0.0
Eye Irritation:  0.461 Respiratory Toxicity:  0.474
Drug-induced Neurotoxicity:  0.867 Ototoxicity:  0.592
Hematotoxicity:  0.958 Drug-induced Nephrotoxicity:  0.983
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.38
A549 Cytotoxicity:  0.468 Hek293 Cytotoxicity:  0.767
BCF:   1.614
?
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:   4.481
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.298
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.713
?
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
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[15568798]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. twig n.a. PMID[22474975]
NPO18553.1 Heliopsis helianthoides Under-species n.a. n.a. n.a. n.a. n.a. PMID[24972328]
NPO18553.1 Heliopsis helianthoides Under-species n.a. n.a. n.a. n.a. n.a. PMID[25479041]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[31347365]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[32319765]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[9014350]
NPO25275 Cynoglossum officinale Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO146 Heliotropium indicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18553.1 Heliopsis helianthoides Under-species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO149 Heliotropium europaeum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8442 Heliotropium curassavicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO819 Heliotropium olgae Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO149 Heliotropium europaeum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO819 Heliotropium olgae Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8442 Heliotropium curassavicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3786 Heliotropium arguzioides Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO146 Heliotropium indicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25275 Cynoglossum officinale Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8442 Heliotropium curassavicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO819 Heliotropium olgae Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3786 Heliotropium arguzioides Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO149 Heliotropium europaeum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO146 Heliotropium indicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25275 Cynoglossum officinale Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO149 Heliotropium europaeum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25275 Cynoglossum officinale Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO146 Heliotropium indicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO753 Acanthopanax sessiliflorum n.a. n.a. n.a. n.a. n.a. n.a. Database[TM-MC]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3786 Heliotropium arguzioides Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO149 Heliotropium europaeum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25275 Cynoglossum officinale Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8442 Heliotropium curassavicum Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO819 Heliotropium olgae Species Heliotropiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO146 Heliotropium indicum Species Heliotropiaceae 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
NPT404 Cell line CCRF-CEM Homo sapiens ID50 = 30.0 uM PMID[15658867]
NPT460 Cell line MT2 Homo sapiens ID50 = 2.5 uM PMID[15658867]
NPT190 Organism Human herpesvirus 1 Human herpesvirus 1 EC50 = 2000.0 nM PMID[15658867]
NPT1141 Organism Human herpesvirus 2 Human herpesvirus 2 EC50 = 35000.0 nM PMID[15658867]
NPT963 Organism Hepatitis B virus Hepatitis B virus EC50 > 1000.0 nM PMID[24549242]
NPT191 Organism Hepatitis C virus Hepatitis C virus EC50 > 3000.0 nM PMID[15658867]
NPT191 Organism Hepatitis C virus Hepatitis C virus Inhibition = 64.0 % PMID[15658867]
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 EC50 > 20000.0 nM PMID[15658867]
NPT963 Organism Hepatitis B virus Hepatitis B virus EC50 = 160.0 nM PMID[23465436]
NPT963 Organism Hepatitis B virus Hepatitis B virus Inhibition = 30.0 % PMID[23465436]
NPT963 Organism Hepatitis B virus Hepatitis B virus EC50 = 1000.0 nM PMID[24549242]
NPT963 Organism Hepatitis B virus Hepatitis B virus IC50 = 1000.0 nM PMID[28383274]
NPT963 Organism Hepatitis B virus Hepatitis B virus EC50 = 160.0 nM PMID[36709647]
NPT2 Others Unspecified n.a. EC50 = 7300.0 nM PMID[15658867]
NPT2 Others Unspecified n.a. EC50 > 2500.0 nM PMID[15658867]
NPT2 Others Unspecified n.a. Activity = 15.0 % PMID[25479041]
NPT24647 Cell line HepG2 2.2.15 Homo sapiens CC50 = 6000.0 nM PMID[28383274]

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 = 3.0 ug.mL-1 PMID[9014350]
- Artemia salina LC50 > 500.0 ug.mL-1 PMID[9014350]

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 NPC54179 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
0.7119 Intermediate Similarity NPC24193
0.6885 Remote Similarity NPC127827
0.6308 Remote Similarity NPC602570
0.5775 Remote Similarity NPC605689
0.5679 Remote Similarity NPC193377
0.5385 Remote Similarity NPC181464
0.5373 Remote Similarity NPC78944
0.5373 Remote Similarity NPC15212
0.5224 Remote Similarity NPC299820

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC54179 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