Natural Product: NPC117387

Natural Product IDNPC117387
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KUIRIGZNHOTLPQ-RUDMXATFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14779758
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002507] Homoisoflavonoids

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 KUIRIGZNHOTLPQ-RUDMXATFSA-N
Standard InCHI InChI=1S/C17H14O7/c1-23-17-12(20)6-13-14(16(17)22)15(21)9(7-24-13)4-8-2-3-10(18)11(19)5-8/h2-6,18-20,22H,7H2,1H3/b9-4+
SMILES COc1c(cc2c(C(=O)/C(=C/c3ccc(c(c3)O)O)/CO2)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   1.958
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.993
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.881
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.492 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.811 Fsp3:   0.118
MCE-18:   40.0
?
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:   1
Colloidal aggregators:   0.854 Fluc inhibitor:   0.681
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.66
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.593
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.307 Promiscuous compounds:   0.499

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.169 MDCK Permeability:   -4.822
Pgp-inhibitor:   0.005 Pgp-substrate:   0.01
PAMPA:   0.309
?
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):   0.012
20% Bioavailability (F20%):   0.778 30% Bioavailability (F30%):   0.894
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.629
Plasma Protein Binding (PPB):   97.216% Volume Distribution (VD):   -0.614
Fu: 2.336%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.952
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.51
BSEP inhibitor:   0.095

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.058
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.034
CYP2C9-inhibitor:   0.018 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.14 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.889
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.749
?
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):  8.177 Half-life (T1/2):  1.137

ADMET: Toxicity

hERG Blockers:  0.209 hERG Blockers (10um):  0.492
Human Hepatotoxicity (H-HT):  0.76 Drug-induced Liver Injury (DILI):  0.783
AMES Toxicity:  0.742 Rat Oral Acute Toxicity:  0.756
Maximum Recommended Daily Dose:  0.958 Skin Sensitization:  0.998
Carcinogencity:  0.757 Eye Corrosion:  0.0
Eye Irritation:  0.342 Respiratory Toxicity:  0.408
Drug-induced Neurotoxicity:  0.089 Ototoxicity:  0.775
Hematotoxicity:  0.168 Drug-induced Nephrotoxicity:  0.481
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.338
A549 Cytotoxicity:  0.961 Hek293 Cytotoxicity:  0.896
BCF:   1.24
?
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:   3.783
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.996
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.517
?
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
NPO28718 Penicillium terrestre Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[18163588]
NPO29396 Bidens bipinnata Species Asteraceae Eukaryota n.a. whole plant n.a. PMID[25282892]
NPO29250 Coprinus comatus Species Agaricaceae Eukaryota n.a. n.a. n.a. PMID[26338495]
NPO40241 Hyacinthaceae Species n.a. n.a. n.a. n.a. n.a. PMID[30951308]
NPO29481 Streptomyces reticuli Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29278 Sicyos angulatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29534 Sarcomelicope leiocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28718 Penicillium terrestre Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29250 Coprinus comatus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18245 Coprinellus micaceus Species Psathyrellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29499 Chionodoxa luciliae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29213 Bulbine narcissifolia Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29396 Bidens bipinnata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40241 Hyacinthaceae Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29125 Ulex europaeus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29125 Ulex europaeus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29396 Bidens bipinnata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29125 Ulex europaeus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29396 Bidens bipinnata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18245 Coprinellus micaceus Species Psathyrellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29125 Ulex europaeus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29499 Chionodoxa luciliae n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO29481 Streptomyces reticuli Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO29250 Coprinus comatus Species Agaricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29396 Bidens bipinnata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29534 Sarcomelicope leiocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28718 Penicillium terrestre Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29278 Sicyos angulatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29213 Bulbine narcissifolia Species Asphodelaceae 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
NPT5265 Cell line Y79 Homo sapiens GI50 > 100000.0 nM PMID[30951308]
NPT21798 Cell line ARPE-19 Homo sapiens GI50 > 100000.0 nM PMID[30951308]
NPT2 Others Unspecified n.a. GI50 > 100000.0 nM PMID[30951308]

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 NPC117387 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
0.6842 Remote Similarity NPC54347
0.6842 Remote Similarity NPC472916
0.6667 Remote Similarity NPC170892
0.6207 Remote Similarity NPC95864
0.6066 Remote Similarity NPC482965
0.5806 Remote Similarity NPC482975
0.5806 Remote Similarity NPC482956
0.5574 Remote Similarity NPC3188
0.55 Remote Similarity NPC275055
0.541 Remote Similarity NPC472915
0.5397 Remote Similarity NPC94758
0.5323 Remote Similarity NPC91236
0.5323 Remote Similarity NPC99333
0.5224 Remote Similarity NPC482964
0.5077 Remote Similarity NPC482968

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC117387 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