Natural Product: NPC264083

Natural Product IDNPC264083
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 OVSYWZXDPOVKQU-AWEZNQCLSA-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:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 OVSYWZXDPOVKQU-AWEZNQCLSA-N
Standard InCHI InChI=1S/C15H12O5/c16-9-1-2-12-13(19)7-14(20-15(12)6-9)8-3-10(17)5-11(18)4-8/h1-6,14,16-18H,7H2/t14-/m0/s1
SMILES c1cc2C(=O)C[C@@H](c3cc(cc(c3)O)O)Oc2cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.07 Volume:   267.823
?
Van der Waals volume.
Dense:   1.016 LogP:   2.307
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.453
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.573
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.742 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.95 Fsp3:   0.133
MCE-18:   55.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.607 Fluc inhibitor:   0.751
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.149
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.255
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.477 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.945 MDCK Permeability:   -4.743
Pgp-inhibitor:   0.246 Pgp-substrate:   0.033
PAMPA:   0.566
?
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):   0.0
20% Bioavailability (F20%):   0.008 30% Bioavailability (F30%):   0.737
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.643
Plasma Protein Binding (PPB):   88.007% Volume Distribution (VD):   -0.147
Fu: 16.203%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.986
BSEP inhibitor:   0.591

ADMET: Metabolism

CYP1A2-inhibitor:   0.406 CYP1A2-substrate:   0.955
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.017 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.54
CYP3A4-inhibitor:   0.258 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.992
HLM stability:   0.756
?
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):  7.685 Half-life (T1/2):  1.844

ADMET: Toxicity

hERG Blockers:  0.187 hERG Blockers (10um):  0.578
Human Hepatotoxicity (H-HT):  0.651 Drug-induced Liver Injury (DILI):  0.226
AMES Toxicity:  0.716 Rat Oral Acute Toxicity:  0.433
Maximum Recommended Daily Dose:  0.815 Skin Sensitization:  0.722
Carcinogencity:  0.82 Eye Corrosion:  0.109
Eye Irritation:  0.998 Respiratory Toxicity:  0.245
Drug-induced Neurotoxicity:  0.67 Ototoxicity:  0.166
Hematotoxicity:  0.061 Drug-induced Nephrotoxicity:  0.144
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.267 Hek293 Cytotoxicity:  0.867
BCF:   1.048
?
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:   3.497
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.469
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.005
?
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
NPO25111 Streptomyces tanashiensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. DOI[10.1016/S0040-4039(01)84249-0]
NPO24121 Vernoniopsis caudata n.a. n.a. n.a. n.a. n.a. n.a. PMID[15921436]
NPO20815 Lindera fruticosa Species Lauraceae Eukaryota roots n.a. n.a. PMID[16724860]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[26509914]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO16971 Sparassis crispa Species Sparassidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21683 Selaginella lepidophylla Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25111 Streptomyces tanashiensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23376 Genista aetnensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23843 Clerodendrum grayi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20815 Lindera fruticosa Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14448 Laurencia venusta Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23948 Serratia plymuthica Species Yersiniaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22722 Ranunculus japonicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22722 Ranunculus japonicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24776 Euryops jacksonii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18589 Allopora californica n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO22722 Ranunculus japonicus Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21121 Ips japonicus Species Curculionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23948 Serratia plymuthica Species Yersiniaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO24411 Pentaspadon motleyi Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23676 Fleroya rubrostipulata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20815 Lindera fruticosa Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14448 Laurencia venusta Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23843 Clerodendrum grayi Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20362 Ruta montana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23158 Penicillium carminoviolaceum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24121 Vernoniopsis caudata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23376 Genista aetnensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17668 Artemisia gmelinii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20226 Artemisia filatovae Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22713 Aquilegia flabellata Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20936 Arecastrum romanzoffianum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO21683 Selaginella lepidophylla Species Selaginellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21787 Betula pubescens Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16184 Asclepias asperula Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24560 Ricinus communis Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16971 Sparassis crispa Species Sparassidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23445 Vernonia triflosculosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13388 Lithophyllum incrustans Species Corallinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25111 Streptomyces tanashiensis Species Streptomycetaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 2.0 % PMID[28522265]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.54 n.a. PMID[28835349]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens GI = 13.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 4.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 0.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 15.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 1.0 % PMID[28522265]
NPT2 Others Unspecified n.a. Inhibition = 12.0 % PMID[28522265]

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 NPC264083 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
0.7955 Intermediate Similarity NPC329225
0.7955 Intermediate Similarity NPC147686
0.766 Intermediate Similarity NPC1612
0.766 Intermediate Similarity NPC183959
0.7609 Intermediate Similarity NPC476480
0.7609 Intermediate Similarity NPC84585
0.7083 Intermediate Similarity NPC472460
0.6531 Remote Similarity NPC182421
0.6364 Remote Similarity NPC143896
0.614 Remote Similarity NPC221432
0.614 Remote Similarity NPC257097
0.6102 Remote Similarity NPC474033
0.6034 Remote Similarity NPC68104
0.6 Remote Similarity NPC23728
0.5849 Remote Similarity NPC73028
0.5806 Remote Similarity NPC474034
0.5769 Remote Similarity NPC32441
0.5769 Remote Similarity NPC79943
0.5645 Remote Similarity NPC291508
0.5577 Remote Similarity NPC225153
0.5577 Remote Similarity NPC479876
0.5522 Remote Similarity NPC209040
0.5455 Remote Similarity NPC321011
0.5455 Remote Similarity NPC294852
0.5455 Remote Similarity NPC210084
0.5455 Remote Similarity NPC188679
0.5303 Remote Similarity NPC170475
0.5294 Remote Similarity NPC110303
0.5294 Remote Similarity NPC601247
0.5273 Remote Similarity NPC324386
0.5185 Remote Similarity NPC295261
0.5185 Remote Similarity NPC243083
0.5185 Remote Similarity NPC13768
0.5185 Remote Similarity NPC296490
0.5185 Remote Similarity NPC287246
0.5179 Remote Similarity NPC486095
0.5167 Remote Similarity NPC39329
0.5167 Remote Similarity NPC51032
0.5094 Remote Similarity NPC265871
0.5094 Remote Similarity NPC205093

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC264083 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
0.7955 Intermediate Similarity NPD1549 Phase 2
0.5769 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5185 Remote Similarity NPD1550 Phase 2

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