Natural Product: NPC249624

Natural Product IDNPC249624
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PWXVHDBBWJSGOT-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101931848
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000325] Biphenols

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 PWXVHDBBWJSGOT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O6/c1-7(17)9-5-6-12(19)13(14(9)20)11-4-3-10(8(2)18)15(21)16(11)22/h3-6,19-22H,1-2H3
SMILES CC(=O)c1ccc(c(c2ccc(C(=O)C)c(c2O)O)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   299.829
?
Van der Waals volume.
Dense:   1.008 LogP:   1.902
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.228
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.48
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   115.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.511 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.513 Fsp3:   0.125
MCE-18:   16.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.528 Fluc inhibitor:   0.062
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.313
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.034
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.687 Promiscuous compounds:   0.338

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.046 MDCK Permeability:   -4.767
Pgp-inhibitor:   0.004 Pgp-substrate:   0.005
PAMPA:   0.878
?
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):   0.026
20% Bioavailability (F20%):   0.06 30% Bioavailability (F30%):   0.154
50% Bioavailability (F50%):   0.78

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.978
Plasma Protein Binding (PPB):   96.37% Volume Distribution (VD):   -0.613
Fu: 3.604%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.95
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.001
BSEP inhibitor:   0.029

ADMET: Metabolism

CYP1A2-inhibitor:   0.023 CYP1A2-substrate:   0.607
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.602
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.998
HLM stability:   0.996
?
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):  2.984 Half-life (T1/2):  1.715

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.384
Human Hepatotoxicity (H-HT):  0.512 Drug-induced Liver Injury (DILI):  0.265
AMES Toxicity:  0.588 Rat Oral Acute Toxicity:  0.226
Maximum Recommended Daily Dose:  0.501 Skin Sensitization:  0.517
Carcinogencity:  0.385 Eye Corrosion:  0.004
Eye Irritation:  0.977 Respiratory Toxicity:  0.859
Drug-induced Neurotoxicity:  0.104 Ototoxicity:  0.337
Hematotoxicity:  0.317 Drug-induced Nephrotoxicity:  0.314
Genotoxicity:  0.821 RPMI-8226 Immunitoxicity:  0.246
A549 Cytotoxicity:  0.512 Hek293 Cytotoxicity:  0.499
BCF:   0.771
?
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:   3.617
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.277
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.773
?
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
NPO8680 Polypodium niponicum Species Polypodiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)80275-7]
NPO8809 Cynanchum wilfordii Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[10217732]
NPO626 Indigofera tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16644212]
NPO280 Dysidea chlorea Species Dysideidae Eukaryota n.a. Okinawan n.a. PMID[16872148]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota Roots n.a. n.a. PMID[24054487]
NPO55 Croton urucurana Species Euphorbiaceae Eukaryota n.a. twig n.a. PMID[24354204]
NPO55 Croton urucurana Species Euphorbiaceae Eukaryota n.a. leaf n.a. PMID[24354204]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota roots n.a. n.a. PMID[24412339]
NPO55 Croton urucurana Species Euphorbiaceae Eukaryota Latex n.a. n.a. PMID[26561866]
NPO8809 Cynanchum wilfordii Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[26716755]
NPO12693 Mesembryanthemum tortuosum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8680 Polypodium niponicum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7220 Artemisia latifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8942 Hedysarum coronarium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8276 Harpullia ramiflora Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3834 Periplaneta americana Species Blattoidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO280 Dysidea chlorea Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6312 Picea engelmannii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6086 Axinella polypoides Species Axinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5745 Randia formosa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2641 Marsupella aquatica Species Gymnomitriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO626 Indigofera tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12693 Mesembryanthemum tortuosum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8680 Polypodium niponicum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12693 Mesembryanthemum tortuosum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5745 Randia formosa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO626 Indigofera tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8680 Polypodium niponicum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8680 Polypodium niponicum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8809 Cynanchum wilfordii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8276 Harpullia ramiflora Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4983 Bromelia pinguin Species Bromeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6086 Axinella polypoides Species Axinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO55 Croton urucurana Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12693 Mesembryanthemum tortuosum Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4010 Flemingia philippinensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7220 Artemisia latifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8942 Hedysarum coronarium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3834 Periplaneta americana Species Blattoidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1017 Dendrobium gibsonii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6312 Picea engelmannii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8809 Cynanchum wilfordii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8407 Polyporus fomentarius Species Polyporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28100 Jacobaea othonnae Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2641 Marsupella aquatica Species Gymnomitriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8531 Centaurea ferox Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO626 Indigofera tinctoria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23643 Thalictrum aquilegiifolium Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5745 Randia formosa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5486 Helicoon richonis Species Orbiliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO280 Dysidea chlorea Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8680 Polypodium niponicum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13333 Paenibacillus thiaminolyticus Species Paenibacillaceae Bacteria 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 NPC249624 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 NPC249624 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