Natural Product: NPC190310

Natural Product IDNPC190310
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NJMLHRWYACXVHJ-IFUGULHKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 497202
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001983] Dihydrofurans
        • [CHEMONTID:0001982] Furanones
          • [CHEMONTID:0002223] Butenolides

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 NJMLHRWYACXVHJ-IFUGULHKSA-N
Standard InCHI InChI=1S/C15H16O4/c1-8-7-17-11-6-15(2)12(19-15)4-3-9-5-10(13(8)11)18-14(9)16/h5,7,10,12H,3-4,6H2,1-2H3/t10-,12+,15-/m1/s1
SMILES Cc1coc2C[C@]3(C)[C@H](CCC4=C[C@H](c12)OC4=O)O3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.1 Volume:   258.385
?
Van der Waals volume.
Dense:   1.007 LogP:   1.566
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.723
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.662
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   51.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.531 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.726 Fsp3:   0.533
MCE-18:   77.478
?
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:   0.437 Fluc inhibitor:   0.383
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.281
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.2
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.271 Promiscuous compounds:   0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.52 MDCK Permeability:   -4.54
Pgp-inhibitor:   0.819 Pgp-substrate:   0.974
PAMPA:   0.108
?
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):   0.001
20% Bioavailability (F20%):   0.487 30% Bioavailability (F30%):   0.863
50% Bioavailability (F50%):   0.926

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.84 MRP1:   0.987
Plasma Protein Binding (PPB):   87.29% Volume Distribution (VD):   -0.295
Fu: 10.292%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.908
OATP1B3 inhibitor:   0.297 BCRP inhibitor:   0.255
BSEP inhibitor:   0.984

ADMET: Metabolism

CYP1A2-inhibitor:   0.667 CYP1A2-substrate:   0.973
CYP2C19-inhibitor:   0.857 CYP2C19-substrate:   0.58
CYP2C9-inhibitor:   0.335 CYP2C9-substrate:   0.018
CYP2D6-inhibitor:   0.356 CYP2D6-substrate:   0.5
CYP3A4-inhibitor:   0.993 CYP3A4-substrate:   0.544
CYP2B6-substrate:   0.707 CYP2C8-inhibitor:   0.981
HLM stability:   0.997
?
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):  8.081 Half-life (T1/2):  1.233

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.489
Human Hepatotoxicity (H-HT):  0.711 Drug-induced Liver Injury (DILI):  0.948
AMES Toxicity:  0.926 Rat Oral Acute Toxicity:  0.802
Maximum Recommended Daily Dose:  0.709 Skin Sensitization:  0.991
Carcinogencity:  0.891 Eye Corrosion:  0.078
Eye Irritation:  0.892 Respiratory Toxicity:  0.47
Drug-induced Neurotoxicity:  0.738 Ototoxicity:  0.403
Hematotoxicity:  0.427 Drug-induced Nephrotoxicity:  0.816
Genotoxicity:  0.967 RPMI-8226 Immunitoxicity:  0.16
A549 Cytotoxicity:  0.265 Hek293 Cytotoxicity:  0.322
BCF:   1.362
?
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:   3.994
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.259
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.947
?
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
NPO15351 Streptomyces prunicolor Species Streptomycetaceae Bacteria n.a. mycelium n.a. DOI[10.1021/np50098a008]
NPO12553 Lindera chunii Species Lauraceae Eukaryota n.a. root n.a. PMID[12237535]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota roots n.a. n.a. PMID[12444706]
NPO11093 Pseudobersama mossambicensis Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[1479381]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[20000780]
NPO11898 Lobophora variegata Species Dictyotaceae Eukaryota n.a. at depths of 630 m at El Mdano (Tenerife, Canary Islands) n.a. PMID[26126835]
NPO5247 Elaphoglossum lindbergii Species Dryopteridaceae Eukaryota n.a. n.a. n.a. PMID[26689830]
NPO2996 Pistacia atlantica Species Anacardiaceae Eukaryota n.a. n.a. n.a. PMID[38202742]
NPO12553 Lindera chunii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15351 Streptomyces prunicolor Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO1116 Periconia atropurpurea Species Periconiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10530 Aconitum subcuneatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1044 Caiman crocodilus Species Alligatoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9606 Castanea dentata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5247 Elaphoglossum lindbergii Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11527 Ibacus peronii Species Scyllaridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6696 Chukrasia tabularis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11206 Trifolium hybridum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7560 Tachardia acaciae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO12146 Stemodia maritima Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2207 Sphaerella rubella n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5714 Rogeria adenophylla Species Pedaliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12633 Rapanea neurophylla Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2996 Pistacia atlantica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23883 Penicillium abidjanum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11898 Lobophora variegata Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12853 Leucocarpus perfoliatus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9363 Ferula ammoniacum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12853 Leucocarpus perfoliatus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12633 Rapanea neurophylla Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10530 Aconitum subcuneatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12553 Lindera chunii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12633 Rapanea neurophylla Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12853 Leucocarpus perfoliatus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11206 Trifolium hybridum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10530 Aconitum subcuneatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6696 Chukrasia tabularis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12553 Lindera chunii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10530 Aconitum subcuneatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1116 Periconia atropurpurea Species Periconiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9363 Ferula ammoniacum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11527 Ibacus peronii Species Scyllaridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15351 Streptomyces prunicolor Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO12633 Rapanea neurophylla Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2996 Pistacia atlantica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7560 Tachardia acaciae n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO9606 Castanea dentata Species Fagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11206 Trifolium hybridum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12146 Stemodia maritima Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23883 Penicillium abidjanum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12553 Lindera chunii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12853 Leucocarpus perfoliatus Species Phrymaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11093 Pseudobersama mossambicensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1044 Caiman crocodilus Species Alligatoridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10530 Aconitum subcuneatum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2207 Sphaerella rubella n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO11898 Lobophora variegata Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4228 Wickerhamomyces anomalus Species Phaffomycetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6541 Scrophularia buergeriana Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6696 Chukrasia tabularis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5714 Rogeria adenophylla Species Pedaliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5247 Elaphoglossum lindbergii Species Dryopteridaceae 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 NPC190310 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
1.0 High Similarity NPC286130
0.661 Remote Similarity NPC216810

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC190310 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