Natural Product: NPC73464

Natural Product IDNPC73464
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FOJRFMGTQBVGNJ-LCYFTJDESA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 21592416
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles

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 FOJRFMGTQBVGNJ-LCYFTJDESA-N
Standard InCHI InChI=1S/C18H11NO3/c20-11-7-5-10(6-8-11)9-13-16-15(18(22)17(13)21)12-3-1-2-4-14(12)19-16/h1-9,19-20H/b13-9-
SMILES c1ccc2c(c1)c1c(/C(=C/c3ccc(cc3)O)/C(=O)C1=O)[nH]2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   289.07 Volume:   296.661
?
Van der Waals volume.
Dense:   0.974 LogP:   3.029
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.928
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.058
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   23.0
TPSA:   70.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.534 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.43 Fsp3:   0.0
MCE-18:   42.0
?
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:   1
Colloidal aggregators:   0.985 Fluc inhibitor:   0.998
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.492
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.871
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.329 Promiscuous compounds:   0.411

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.056 MDCK Permeability:   -4.773
Pgp-inhibitor:   0.984 Pgp-substrate:   0.0
PAMPA:   0.578
?
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):   0.182
20% Bioavailability (F20%):   0.064 30% Bioavailability (F30%):   0.567
50% Bioavailability (F50%):   0.427

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.03
Plasma Protein Binding (PPB):   97.049% Volume Distribution (VD):   0.176
Fu: 2.792%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.948
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.754 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.565
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.403
?
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):  8.774 Half-life (T1/2):  0.799

ADMET: Toxicity

hERG Blockers:  0.315 hERG Blockers (10um):  0.735
Human Hepatotoxicity (H-HT):  0.985 Drug-induced Liver Injury (DILI):  0.8
AMES Toxicity:  0.933 Rat Oral Acute Toxicity:  0.829
Maximum Recommended Daily Dose:  0.937 Skin Sensitization:  1.0
Carcinogencity:  0.839 Eye Corrosion:  0.0
Eye Irritation:  0.922 Respiratory Toxicity:  0.328
Drug-induced Neurotoxicity:  0.782 Ototoxicity:  0.67
Hematotoxicity:  0.812 Drug-induced Nephrotoxicity:  0.952
Genotoxicity:  0.969 RPMI-8226 Immunitoxicity:  0.241
A549 Cytotoxicity:  0.62 Hek293 Cytotoxicity:  0.888
BCF:   1.392
?
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:   4.65
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.578
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.365
?
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
NPO18618 Neurolaena lobata Species Asteraceae Eukaryota n.a. aerial part n.a. DOI[10.1021/jo00416a020]
NPO3613 Eriobotrya deflexa Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[11473413]
NPO4541 Capnella lacertiliensis Species Nephtheidae Eukaryota n.a. n.a. n.a. PMID[12608844]
NPO8945 Grevillea robusta Species Proteaceae Eukaryota leaves n.a. n.a. PMID[17243726]
NPO18618 Neurolaena lobata Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO18618 Neurolaena lobata Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[24476550]
NPO23436 Cladrastis sikokiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1537 Vaccinium arctostaphylos Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8426 Tinospora rumphii Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8945 Grevillea robusta Species Proteaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8305 Katsuwonus pelamis Species Scombridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4198 Ungernia vvedenskyi Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1969 Streptomyces pilosus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12744 Ajuga nipponensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8623 Anneissia japonica Species Comatulidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4541 Capnella lacertiliensis Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7788 Rana catesbeiana Species Ranidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8811 Cytisus prolifer Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28833 Eleutherococcus sieboldianus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3613 Eriobotrya deflexa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10879 Lasius meridionalis Species Formicidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19804 Lycopodium saururus Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9705 Meyerozyma guilliermondii Species Debaryomycetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19541 Smilax moranensis Species Smilacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18618 Neurolaena lobata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7240 Osteospermum oppositifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO834 Peperomia clusiifolia Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8305 Katsuwonus pelamis Species Scombridae Eukaryota n.a. n.a. Database[FooDB]
NPO8945 Grevillea robusta Species Proteaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3613 Eriobotrya deflexa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12744 Ajuga nipponensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8945 Grevillea robusta Species Proteaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8945 Grevillea robusta Species Proteaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7240 Osteospermum oppositifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1969 Streptomyces pilosus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO8426 Tinospora rumphii Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8305 Katsuwonus pelamis Species Scombridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4541 Capnella lacertiliensis Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7788 Rana catesbeiana Species Ranidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18618 Neurolaena lobata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8623 Anneissia japonica Species Comatulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5335 Nostoc sp Species Nostocaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO28833 Eleutherococcus sieboldianus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1537 Vaccinium arctostaphylos Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10879 Lasius meridionalis Species Formicidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4198 Ungernia vvedenskyi Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12744 Ajuga nipponensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23436 Cladrastis sikokiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8945 Grevillea robusta Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8811 Cytisus prolifer Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19804 Lycopodium saururus Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO834 Peperomia clusiifolia Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9705 Meyerozyma guilliermondii Species Debaryomycetaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3613 Eriobotrya deflexa Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19541 Smilax moranensis Species Smilacaceae 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 NPC73464 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC73464 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