Natural Product: NPC221850

Natural Product IDNPC221850
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CGGSDUVYXCMYHX-BTDLBPIBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101663167
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran 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 CGGSDUVYXCMYHX-BTDLBPIBSA-N
Standard InCHI InChI=1S/C18H18O5/c1-10-13-6-11(9-19)7-16(22-3)18(13)23-17(10)12-4-5-14(20)15(8-12)21-2/h4-10,17,20H,1-3H3/t10-,17-/m0/s1
SMILES C[C@H]1c2cc(cc(c2O[C@@H]1c1ccc(c(c1)OC)O)OC)C=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.12 Volume:   319.711
?
Van der Waals volume.
Dense:   0.983 LogP:   2.679
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.801
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.167
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   64.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.876 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.202 Fsp3:   0.278
MCE-18:   57.13
?
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:   0
Colloidal aggregators:   0.616 Fluc inhibitor:   0.514
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.129
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.567
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.37 Promiscuous compounds:   0.158

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.079 MDCK Permeability:   -4.886
Pgp-inhibitor:   0.775 Pgp-substrate:   0.052
PAMPA:   0.008
?
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):   0.004
20% Bioavailability (F20%):   0.253 30% Bioavailability (F30%):   0.263
50% Bioavailability (F50%):   0.898

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.392 MRP1:   0.734
Plasma Protein Binding (PPB):   91.933% Volume Distribution (VD):   -0.221
Fu: 8.642%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.853
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.143
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.715
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.049
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.621
CYP3A4-inhibitor:   0.994 CYP3A4-substrate:   0.862
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.992
HLM stability:   0.037
?
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):  8.129 Half-life (T1/2):  1.486

ADMET: Toxicity

hERG Blockers:  0.177 hERG Blockers (10um):  0.597
Human Hepatotoxicity (H-HT):  0.556 Drug-induced Liver Injury (DILI):  0.256
AMES Toxicity:  0.584 Rat Oral Acute Toxicity:  0.431
Maximum Recommended Daily Dose:  0.506 Skin Sensitization:  0.577
Carcinogencity:  0.512 Eye Corrosion:  0.365
Eye Irritation:  0.977 Respiratory Toxicity:  0.719
Drug-induced Neurotoxicity:  0.525 Ototoxicity:  0.29
Hematotoxicity:  0.284 Drug-induced Nephrotoxicity:  0.355
Genotoxicity:  0.342 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.201 Hek293 Cytotoxicity:  0.435
BCF:   1.088
?
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:   3.673
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.935
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.437
?
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
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[27142697]
NPO5146 Tuta absoluta Species Gelechiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27130 Tsuga sieboldii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27570 Paederia foetida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26934 Naucleopsis mello-barretoi Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27635 Laurencia dendroidea Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27339 Lactarius blennius Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16221 Dolichos kilimandscharicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27777 Artemisia phaeolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27593 Silene dioica Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27520 Casuarina equisetifolia Species Casuarinaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27130 Tsuga sieboldii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16221 Dolichos kilimandscharicus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27339 Lactarius blennius Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27635 Laurencia dendroidea Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27570 Paederia foetida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27742 Mollugo pentaphylla Species Molluginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27593 Silene dioica Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27465 Sinularia erecta Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26934 Naucleopsis mello-barretoi Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5146 Tuta absoluta Species Gelechiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27777 Artemisia phaeolepis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27520 Casuarina equisetifolia Species Casuarinaceae 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 NPC221850 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
0.7736 Intermediate Similarity NPC300757
0.7692 Intermediate Similarity NPC131121
0.7222 Intermediate Similarity NPC187616
0.7222 Intermediate Similarity NPC193026
0.7222 Intermediate Similarity NPC49603
0.6562 Remote Similarity NPC480704
0.569 Remote Similarity NPC154258
0.5667 Remote Similarity NPC180901
0.5645 Remote Similarity NPC29799
0.5645 Remote Similarity NPC263367
0.5645 Remote Similarity NPC177160
0.5645 Remote Similarity NPC54743
0.5556 Remote Similarity NPC472961
0.5556 Remote Similarity NPC472962
0.5469 Remote Similarity NPC284881
0.5469 Remote Similarity NPC93433
0.5469 Remote Similarity NPC474444
0.5397 Remote Similarity NPC156502
0.5397 Remote Similarity NPC10737
0.5352 Remote Similarity NPC43065
0.5303 Remote Similarity NPC206413
0.5303 Remote Similarity NPC482649
0.5303 Remote Similarity NPC149003
0.5303 Remote Similarity NPC482647
0.5303 Remote Similarity NPC482648
0.5303 Remote Similarity NPC482651
0.5303 Remote Similarity NPC194244
0.5303 Remote Similarity NPC482650
0.5294 Remote Similarity NPC131971
0.5294 Remote Similarity NPC15189
0.5294 Remote Similarity NPC480707
0.5254 Remote Similarity NPC98745
0.5254 Remote Similarity NPC115663
0.5075 Remote Similarity NPC253878
0.5075 Remote Similarity NPC471414

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC221850 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