Natural Product: NPC253622

Natural Product IDNPC253622
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XCJSWJPRPDMYLS-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14630664
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000025] Phenanthrenes and derivatives
        • [CHEMONTID:0003007] Phenanthrols

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 XCJSWJPRPDMYLS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H18O4/c1-26-21-12-20(25)19(10-13-2-5-15(23)6-3-13)18-8-4-14-11-16(24)7-9-17(14)22(18)21/h2-9,11-12,23-25H,10H2,1H3
SMILES COc1cc(c(Cc2ccc(cc2)O)c2ccc3cc(ccc3c12)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.12 Volume:   363.639
?
Van der Waals volume.
Dense:   0.952 LogP:   3.733
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.619
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.685
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   69.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.47 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.332 Fsp3:   0.091
MCE-18:   22.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.986 Fluc inhibitor:   0.465
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.749
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.477
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.395 Promiscuous compounds:   0.132

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.917 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.002 Pgp-substrate:   0.177
PAMPA:   0.861
?
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):   0.002
20% Bioavailability (F20%):   0.643 30% Bioavailability (F30%):   0.593
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.918
Plasma Protein Binding (PPB):   93.835% Volume Distribution (VD):   0.004
Fu: 9.102%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.021
BSEP inhibitor:   0.943

ADMET: Metabolism

CYP1A2-inhibitor:   0.328 CYP1A2-substrate:   0.481
CYP2C19-inhibitor:   0.34 CYP2C19-substrate:   0.805
CYP2C9-inhibitor:   0.719 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.908
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.948
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.988
HLM stability:   0.649
?
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):  7.883 Half-life (T1/2):  1.212

ADMET: Toxicity

hERG Blockers:  0.25 hERG Blockers (10um):  0.796
Human Hepatotoxicity (H-HT):  0.619 Drug-induced Liver Injury (DILI):  0.326
AMES Toxicity:  0.693 Rat Oral Acute Toxicity:  0.301
Maximum Recommended Daily Dose:  0.739 Skin Sensitization:  0.869
Carcinogencity:  0.709 Eye Corrosion:  0.032
Eye Irritation:  0.991 Respiratory Toxicity:  0.971
Drug-induced Neurotoxicity:  0.702 Ototoxicity:  0.233
Hematotoxicity:  0.141 Drug-induced Nephrotoxicity:  0.15
Genotoxicity:  0.705 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.479 Hek293 Cytotoxicity:  0.898
BCF:   1.44
?
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:   4.545
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.226
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.892
?
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
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[1402962]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[15686910]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[15921416]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. subtidal zone (0-2 m) off the southwestern shore of Jeju Island, Korea 2003-Apr PMID[18817444]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[19006667]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[21377877]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota Fibrous Roots n.a. n.a. PMID[25760525]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Flower Buds n.a. n.a. PMID[26977531]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota Rhizomes n.a. n.a. PMID[27525452]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. PMID[28720331]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[31415170]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[34770801]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36985392]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[37836118]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39684253]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39699537]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[8904847]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11479 Sargassum siliquastrum Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7428 Bletilla formosana Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10780 Bletilla striata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8787 Ariocarpus scapharostrus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3987 Syzygium aromaticum Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15591 Tolpis webbii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11479 Sargassum siliquastrum Species Sargassaceae 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
NPT34 Cell line BV-2 Mus musculus IC50 = 30200.0 nM PMID[31415170]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 500.0 nM PMID[27525452]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 900.0 nM PMID[27525452]

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 NPC253622 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
0.75 Intermediate Similarity NPC480636
0.7143 Intermediate Similarity NPC183709
0.7143 Intermediate Similarity NPC478411
0.5902 Remote Similarity NPC478410
0.5577 Remote Similarity NPC53781

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC253622 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