Natural Product: NPC80007

Natural Product IDNPC80007
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KJUMUMWJYIOICG-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 KJUMUMWJYIOICG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-7-3-2-4-9(18)12(7)16-15(21)14(20)13-10(19)5-8(17)6-11(13)22-16/h2-6,17-19,21H,1H3
SMILES Cc1cccc(c1c1c(c(=O)c2c(cc(cc2o1)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   2.054
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.067
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.213
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.549 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.599 Fsp3:   0.062
MCE-18:   19.0
?
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:   0
Colloidal aggregators:   0.805 Fluc inhibitor:   0.547
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.822
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.423
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.509 Promiscuous compounds:   0.722

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.402 MDCK Permeability:   -4.848
Pgp-inhibitor:   0.163 Pgp-substrate:   0.468
PAMPA:   0.739
?
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):   0.061
20% Bioavailability (F20%):   0.072 30% Bioavailability (F30%):   0.561
50% Bioavailability (F50%):   0.938

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.919
Plasma Protein Binding (PPB):   96.611% Volume Distribution (VD):   -0.463
Fu: 2.502%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.64
OATP1B3 inhibitor:   0.917 BCRP inhibitor:   0.834
BSEP inhibitor:   0.604

ADMET: Metabolism

CYP1A2-inhibitor:   0.91 CYP1A2-substrate:   0.757
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.688
CYP2C9-inhibitor:   0.957 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.846
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.009
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.998
?
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):  4.85 Half-life (T1/2):  1.203

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.43
Human Hepatotoxicity (H-HT):  0.409 Drug-induced Liver Injury (DILI):  0.584
AMES Toxicity:  0.587 Rat Oral Acute Toxicity:  0.468
Maximum Recommended Daily Dose:  0.695 Skin Sensitization:  0.684
Carcinogencity:  0.657 Eye Corrosion:  0.437
Eye Irritation:  0.997 Respiratory Toxicity:  0.856
Drug-induced Neurotoxicity:  0.021 Ototoxicity:  0.09
Hematotoxicity:  0.078 Drug-induced Nephrotoxicity:  0.049
Genotoxicity:  0.9 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.358 Hek293 Cytotoxicity:  0.627
BCF:   1.121
?
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:   3.886
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.745
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.295
?
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
NPO11748 Eunicea knighti Species Plexauridae Eukaryota n.a. Santa Marta Bay, Colombian Caribbean 2007-MAY PMID[19778088]
NPO17543 Stizophyllum riparium Species Bignoniaceae Eukaryota n.a. n.a. n.a. PMID[3598599]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. kernel n.a. PMID[7092570]
NPO17543 Stizophyllum riparium Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11748 Eunicea knighti Species Plexauridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16610 Chromodoris hamiltoni Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14992 Prunus persica Species Rosaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO14992 Prunus persica Species Rosaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO14992 Prunus persica Species Rosaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO14992 Prunus persica Species Rosaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14992 Prunus persica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17543 Stizophyllum riparium Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14691.1 Crambe hispanica subsp. abyssinica Subspecies Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15658 Utricularia vulgaris Species Lentibulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11748 Eunicea knighti Species Plexauridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3962 Parinari campestris Species Chrysobalanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16730 Helichrysum lindleyi Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16610 Chromodoris hamiltoni Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17023 Cusparia macrocarpa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26084 Vincetoxicum amplexicaule Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14992 Prunus persica Species Rosaceae 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 NPC80007 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
0.6923 Remote Similarity NPC601197
0.6667 Remote Similarity NPC256042
0.6182 Remote Similarity NPC179271
0.6182 Remote Similarity NPC216361
0.6111 Remote Similarity NPC116775
0.6111 Remote Similarity NPC187432
0.6 Remote Similarity NPC20791
0.5714 Remote Similarity NPC169749
0.5593 Remote Similarity NPC219330
0.55 Remote Similarity NPC50403
0.55 Remote Similarity NPC241838
0.55 Remote Similarity NPC28274
0.5397 Remote Similarity NPC125062
0.5333 Remote Similarity NPC605617
0.5323 Remote Similarity NPC54394
0.5323 Remote Similarity NPC159103
0.5303 Remote Similarity NPC205046
0.5238 Remote Similarity NPC609179
0.5224 Remote Similarity NPC200694
0.5156 Remote Similarity NPC133953

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC80007 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
0.6 Remote Similarity NPD1512 Phase 3

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