Natural Product: NPC479117

Natural Product IDNPC479117
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BMLIIPOXVWESJG-CMIZNHKFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12442781
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 BMLIIPOXVWESJG-CMIZNHKFSA-N
Standard InCHI InChI=1S/C25H22O10/c1-33-18-6-10(2-3-15(18)28)23-14(9-26)13-4-11(5-17(30)25(13)35-23)24-22(32)21(31)20-16(29)7-12(27)8-19(20)34-24/h2-8,14,22-24,26-30,32H,9H2,1H3/t14?,22-,23?,24+/m0/s1
SMILES COc1cc(ccc1O)C1C(CO)c2cc(cc(c2O1)O)[C@@H]1[C@H](C(=O)c2c(cc(cc2O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   482.12 Volume:   459.711
?
Van der Waals volume.
Dense:   1.049 LogP:   1.168
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.419
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.121
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   28.0
TPSA:   166.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   5.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.325 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.199 Fsp3:   0.24
MCE-18:   101.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.638 Fluc inhibitor:   0.116
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.257
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.717
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.47 Promiscuous compounds:   0.102

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.154 MDCK Permeability:   -5.131
Pgp-inhibitor:   0.173 Pgp-substrate:   0.295
PAMPA:   0.504
?
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):   0.055
20% Bioavailability (F20%):   0.122 30% Bioavailability (F30%):   0.992
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.914
Plasma Protein Binding (PPB):   92.84% Volume Distribution (VD):   0.076
Fu: 7.112%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.917
BSEP inhibitor:   0.181

ADMET: Metabolism

CYP1A2-inhibitor:   0.024 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.066
CYP2C9-inhibitor:   0.372 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.594 CYP3A4-substrate:   0.27
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.985
HLM stability:   0.252
?
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):  6.178 Half-life (T1/2):  2.088

ADMET: Toxicity

hERG Blockers:  0.09 hERG Blockers (10um):  0.444
Human Hepatotoxicity (H-HT):  0.914 Drug-induced Liver Injury (DILI):  0.723
AMES Toxicity:  0.719 Rat Oral Acute Toxicity:  0.647
Maximum Recommended Daily Dose:  0.763 Skin Sensitization:  0.975
Carcinogencity:  0.366 Eye Corrosion:  0.0
Eye Irritation:  0.773 Respiratory Toxicity:  0.643
Drug-induced Neurotoxicity:  0.252 Ototoxicity:  0.747
Hematotoxicity:  0.33 Drug-induced Nephrotoxicity:  0.887
Genotoxicity:  0.98 RPMI-8226 Immunitoxicity:  0.325
A549 Cytotoxicity:  0.937 Hek293 Cytotoxicity:  0.893
BCF:   0.799
?
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:   3.438
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.618
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.9
?
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
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1080/10496475.2013.791908]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. whole plant n.a. PMID[16394559]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[24456525]
NPO5645 Silybum marianum Species Asteraceae Eukaryota Seeds n.a. n.a. PMID[24597776]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5645 Silybum marianum Species Asteraceae 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
NPT27 Others Unspecified n.a. Ki = 40270.0 nM PMID[9406602]
NPT2 Others Unspecified n.a. IC50 = 10300.0 nM PMID[28006905]
NPT35 Others n.a. n.a. IC50 = 18970.0 nM PMID[28006905]
NPT35 Others n.a. n.a. Activity = 1.49 equiv PMID[28006905]
NPT35 Others n.a. n.a. Activity = 1.09 equiv PMID[28006905]

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 NPC479117 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
1.0 High Similarity NPC279209
1.0 High Similarity NPC102277
0.7534 Intermediate Similarity NPC606364
0.7368 Intermediate Similarity NPC602605
0.7164 Intermediate Similarity NPC326037
0.7164 Intermediate Similarity NPC13858
0.6143 Remote Similarity NPC320825
0.6049 Remote Similarity NPC36916
0.6049 Remote Similarity NPC36
0.6049 Remote Similarity NPC7154
0.6049 Remote Similarity NPC125039
0.6049 Remote Similarity NPC7688
0.5976 Remote Similarity NPC138688
0.5976 Remote Similarity NPC72787
0.5976 Remote Similarity NPC217795
0.5976 Remote Similarity NPC58223
0.5857 Remote Similarity NPC250922
0.5833 Remote Similarity NPC180901
0.5652 Remote Similarity NPC62290
0.5652 Remote Similarity NPC142731
0.5652 Remote Similarity NPC326506
0.5634 Remote Similarity NPC36835
0.5634 Remote Similarity NPC246162
0.5634 Remote Similarity NPC9743
0.5634 Remote Similarity NPC260491
0.5634 Remote Similarity NPC61506
0.5634 Remote Similarity NPC240476
0.5493 Remote Similarity NPC44721
0.5493 Remote Similarity NPC211466
0.5493 Remote Similarity NPC605332
0.5479 Remote Similarity NPC52530
0.5286 Remote Similarity NPC21835
0.5211 Remote Similarity NPC4152
0.519 Remote Similarity NPC209985
0.5139 Remote Similarity NPC19721
0.5128 Remote Similarity NPC472961
0.5128 Remote Similarity NPC472962
0.5114 Remote Similarity NPC75827
0.5067 Remote Similarity NPC16435

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479117 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
0.6049 Remote Similarity NPD6166 Phase 2
0.6049 Remote Similarity NPD6167 Clinical (unspecified phase)
0.6049 Remote Similarity NPD6168 Clinical (unspecified phase)

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