Natural Product: NPC149003

Natural Product IDNPC149003
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DPDJZJNYBSGDHT-DWDFQXMKSA-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: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 DPDJZJNYBSGDHT-DWDFQXMKSA-N
Standard InCHI InChI=1S/C21H22O7/c1-25-17-10-13(5-6-16(17)23)20-15(11-22)14-8-12(4-7-19(24)27-3)9-18(26-2)21(14)28-20/h4-10,15,20,22-23H,11H2,1-3H3/b7-4+/t15-,20-/m1/s1
SMILES COc1cc(ccc1O)[C@@H]1[C@H](CO)c2cc(/C=C/C(=O)OC)cc(c2O1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   386.543
?
Van der Waals volume.
Dense:   0.999 LogP:   2.704
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.719
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.176
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   94.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.582 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.347 Fsp3:   0.286
MCE-18:   59.815
?
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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.778 Fluc inhibitor:   0.997
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.263
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.749
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.265 Promiscuous compounds:   0.447

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.674 MDCK Permeability:   -5.139
Pgp-inhibitor:   0.975 Pgp-substrate:   0.242
PAMPA:   0.032
?
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):   0.006
20% Bioavailability (F20%):   0.458 30% Bioavailability (F30%):   0.516
50% Bioavailability (F50%):   0.977

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.595
Plasma Protein Binding (PPB):   79.811% Volume Distribution (VD):   -0.018
Fu: 22.786%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.928
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.789
CYP2C19-inhibitor:   0.566 CYP2C19-substrate:   0.503
CYP2C9-inhibitor:   0.953 CYP2C9-substrate:   0.057
CYP2D6-inhibitor:   0.952 CYP2D6-substrate:   0.923
CYP3A4-inhibitor:   0.451 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.068
?
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):  6.714 Half-life (T1/2):  1.483

ADMET: Toxicity

hERG Blockers:  0.079 hERG Blockers (10um):  0.396
Human Hepatotoxicity (H-HT):  0.803 Drug-induced Liver Injury (DILI):  0.256
AMES Toxicity:  0.64 Rat Oral Acute Toxicity:  0.338
Maximum Recommended Daily Dose:  0.434 Skin Sensitization:  0.849
Carcinogencity:  0.406 Eye Corrosion:  0.003
Eye Irritation:  0.903 Respiratory Toxicity:  0.119
Drug-induced Neurotoxicity:  0.219 Ototoxicity:  0.589
Hematotoxicity:  0.316 Drug-induced Nephrotoxicity:  0.754
Genotoxicity:  0.506 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.098 Hek293 Cytotoxicity:  0.33
BCF:   1.039
?
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:   3.623
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.231
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.586
?
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
NPO40145 Gardenia ternifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[28488862]
NPO40145 Gardenia ternifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT165 Cell line HeLa Homo sapiens IC50 = 105000.0 nM PMID[28488862]

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 NPC149003 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 NPC206413
1.0 High Similarity NPC482649
1.0 High Similarity NPC482647
1.0 High Similarity NPC482648
1.0 High Similarity NPC482651
1.0 High Similarity NPC194244
1.0 High Similarity NPC482650
0.8 Intermediate Similarity NPC284881
0.8 Intermediate Similarity NPC93433
0.8 Intermediate Similarity NPC474444
0.7966 Intermediate Similarity NPC156502
0.7966 Intermediate Similarity NPC10737
0.7742 Intermediate Similarity NPC253878
0.7742 Intermediate Similarity NPC471414
0.7231 Intermediate Similarity NPC163898
0.6885 Remote Similarity NPC300757
0.6613 Remote Similarity NPC87725
0.6613 Remote Similarity NPC263261
0.6562 Remote Similarity NPC473408
0.6562 Remote Similarity NPC177160
0.6508 Remote Similarity NPC26394
0.6462 Remote Similarity NPC472961
0.6462 Remote Similarity NPC472962
0.6452 Remote Similarity NPC187616
0.6452 Remote Similarity NPC193026
0.6452 Remote Similarity NPC49603
0.6308 Remote Similarity NPC29799
0.6308 Remote Similarity NPC263367
0.6308 Remote Similarity NPC54743
0.6143 Remote Similarity NPC131971
0.6143 Remote Similarity NPC15189
0.6143 Remote Similarity NPC480707
0.5897 Remote Similarity NPC470769
0.5844 Remote Similarity NPC260397
0.5797 Remote Similarity NPC209985
0.575 Remote Similarity NPC470828
0.573 Remote Similarity NPC228357
0.5584 Remote Similarity NPC236166
0.5584 Remote Similarity NPC480698
0.5517 Remote Similarity NPC107588
0.5517 Remote Similarity NPC137537
0.55 Remote Similarity NPC115203
0.5476 Remote Similarity NPC470827
0.5469 Remote Similarity NPC481090
0.5455 Remote Similarity NPC216916
0.5455 Remote Similarity NPC45943
0.5455 Remote Similarity NPC469889
0.5373 Remote Similarity NPC180901
0.5217 Remote Similarity NPC485396
0.5217 Remote Similarity NPC485394
0.5217 Remote Similarity NPC485395
0.5152 Remote Similarity NPC154258
0.5147 Remote Similarity NPC135127
0.5139 Remote Similarity NPC264706
0.5119 Remote Similarity NPC224674
0.5119 Remote Similarity NPC125495
0.5119 Remote Similarity NPC64475
0.5062 Remote Similarity NPC43508

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC149003 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