Natural Product: NPC21951

Natural Product IDNPC21951
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SSIWKQVIFLSBDM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 13845921
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-O-methylated flavonoids

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 SSIWKQVIFLSBDM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O13S2/c1-26-16-9(18)6-13-14(15(16)19)8(17)5-11(27-13)7-2-3-10(28-30(20,21)22)12(4-7)29-31(23,24)25/h2-6,18-19H,1H3,(H,20,21,22)(H,23,24,25)
SMILES COc1c(cc2c(c(=O)cc(c3ccc(c(c3)OS(=O)(=O)O)OS(=O)(=O)O)o2)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   475.97 Volume:   389.822
?
Van der Waals volume.
Dense:   1.221 LogP:   0.011
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.837
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.67
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   207.1
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   15.0

MedChem Properties

QED Drug-Likeness Score:   0.37 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.912 Fsp3:   0.062
MCE-18:   25.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.319 Fluc inhibitor:   0.465
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.883
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.705
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.593 Promiscuous compounds:   0.299

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.74 MDCK Permeability:   -4.85
Pgp-inhibitor:   0.071 Pgp-substrate:   0.103
PAMPA:   0.638
?
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):   0.42
20% Bioavailability (F20%):   0.81 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.986
Plasma Protein Binding (PPB):   97.994% Volume Distribution (VD):   -0.761
Fu: 1.629%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.63
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.99
BSEP inhibitor:   0.529

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.002
HLM stability:   0.006
?
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):  1.234 Half-life (T1/2):  1.367

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.009
Human Hepatotoxicity (H-HT):  0.563 Drug-induced Liver Injury (DILI):  1.0
AMES Toxicity:  0.058 Rat Oral Acute Toxicity:  0.056
Maximum Recommended Daily Dose:  0.979 Skin Sensitization:  0.979
Carcinogencity:  0.151 Eye Corrosion:  0.976
Eye Irritation:  0.929 Respiratory Toxicity:  0.716
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.12
Hematotoxicity:  0.094 Drug-induced Nephrotoxicity:  0.05
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.001 Hek293 Cytotoxicity:  0.101
BCF:   0.632
?
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:   3.092
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.177
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.058
?
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
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. PMID[18071251]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. faeces n.a. PMID[18323202]
NPO25456 Cortinarius infractus Species Cortinariaceae Eukaryota Toadstool n.a. n.a. PMID[20176490]
NPO25579 Alstonia pneumatophora Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[20576577]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. aerial part n.a. PMID[25140335]
NPO23338 Cribrochalina dura Species Niphatidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25579 Alstonia pneumatophora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25456 Cortinarius infractus Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24451 Gaylussacia frondosa Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24861 Usnea aciculifera Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24959 Chaenomeles cathayensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19268 Climacostomum virens Species Climacostomidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24761 Enicostema littorale Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24904 Mangifera gabonensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25688 Mikania congesta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25551 Monodora grandiflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8634 Podocarpus mannii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25270 Trichoderma roseum Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25066 Werneria stuebelii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10051 Phyla nodiflora Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24451 Gaylussacia frondosa Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25270 Trichoderma roseum Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25579 Alstonia pneumatophora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25456 Cortinarius infractus Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24761 Enicostema littorale Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25688 Mikania congesta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25066 Werneria stuebelii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24959 Chaenomeles cathayensis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19268 Climacostomum virens Species Climacostomidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24904 Mangifera gabonensis Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8634 Podocarpus mannii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23338 Cribrochalina dura Species Niphatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25551 Monodora grandiflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24861 Usnea aciculifera Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10051 Phyla nodiflora Species Verbenaceae 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 NPC21951 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
0.7049 Intermediate Similarity NPC255350
0.6833 Remote Similarity NPC156222
0.6613 Remote Similarity NPC256283
0.6557 Remote Similarity NPC284552
0.6508 Remote Similarity NPC83508
0.6393 Remote Similarity NPC293183
0.6338 Remote Similarity NPC604322
0.629 Remote Similarity NPC241498
0.619 Remote Similarity NPC100887
0.6143 Remote Similarity NPC213622
0.5775 Remote Similarity NPC470402
0.5294 Remote Similarity NPC69394
0.5217 Remote Similarity NPC12200
0.5075 Remote Similarity NPC203891
0.5075 Remote Similarity NPC44079
0.5072 Remote Similarity NPC115798

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC21951 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
0.7049 Intermediate Similarity NPD2801 Pre-clinical

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