Natural Product: NPC488135

Natural Product IDNPC488135
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YJDRRALEPJSKSX-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 21676195
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0001612] Isoflavans
          • [CHEMONTID:0001827] Isoflavanones
            • [CHEMONTID:0003526] 6-prenylated isoflavanones

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 YJDRRALEPJSKSX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H18O4/c1-21(2)9-8-14-10-16-19(11-18(14)25-21)24-12-17(20(16)22)13-4-6-15(23-3)7-5-13/h4-12H,1-3H3
SMILES CC1(C)C=Cc2cc3c(cc2O1)occ(c1ccc(cc1)OC)c3=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   334.12 Volume:   348.979
?
Van der Waals volume.
Dense:   0.957 LogP:   3.984
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.472
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.284
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.684 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.584 Fsp3:   0.19
MCE-18:   47.84
?
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:   0.972 Fluc inhibitor:   0.966
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.955
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.809
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.421 Promiscuous compounds:   0.276

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.73 MDCK Permeability:   -4.731
Pgp-inhibitor:   0.96 Pgp-substrate:   0.006
PAMPA:   0.259
?
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):   0.129
20% Bioavailability (F20%):   0.694 30% Bioavailability (F30%):   0.866
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.025 MRP1:   0.782
Plasma Protein Binding (PPB):   96.879% Volume Distribution (VD):   0.114
Fu: 2.464%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.981
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.739 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.975
CYP2C9-inhibitor:   0.59 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.146 CYP2D6-substrate:   0.036
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.064 CYP2C8-inhibitor:   1.0
HLM stability:   0.103
?
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):  6.701 Half-life (T1/2):  0.548

ADMET: Toxicity

hERG Blockers:  0.328 hERG Blockers (10um):  0.566
Human Hepatotoxicity (H-HT):  0.542 Drug-induced Liver Injury (DILI):  0.792
AMES Toxicity:  0.711 Rat Oral Acute Toxicity:  0.622
Maximum Recommended Daily Dose:  0.73 Skin Sensitization:  0.185
Carcinogencity:  0.89 Eye Corrosion:  0.014
Eye Irritation:  0.857 Respiratory Toxicity:  0.849
Drug-induced Neurotoxicity:  0.672 Ototoxicity:  0.343
Hematotoxicity:  0.323 Drug-induced Nephrotoxicity:  0.501
Genotoxicity:  0.536 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.103 Hek293 Cytotoxicity:  0.378
BCF:   2.037
?
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:   4.55
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.487
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.856
?
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
NPO2722 Humulus japonicus Species Cannabaceae Eukaryota Aerial Parts n.a. n.a. PMID[29254897]
NPO2722 Humulus japonicus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2722 Humulus japonicus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2722 Humulus japonicus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2722 Humulus japonicus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2722 Humulus japonicus Species Cannabaceae 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
NPT43 Individual protein Tyrosinase Agaricus bisporus Inhibition > 30.0 % PMID[29254897]

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 NPC488135 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
0.7538 Intermediate Similarity NPC179970
0.7536 Intermediate Similarity NPC5840
0.7429 Intermediate Similarity NPC78071
0.6615 Remote Similarity NPC607923
0.6167 Remote Similarity NPC182428
0.6032 Remote Similarity NPC474340
0.597 Remote Similarity NPC17262
0.5938 Remote Similarity NPC136095
0.5902 Remote Similarity NPC120924
0.5867 Remote Similarity NPC229847
0.5811 Remote Similarity NPC184755
0.5692 Remote Similarity NPC186507
0.5676 Remote Similarity NPC104406
0.557 Remote Similarity NPC477530
0.5538 Remote Similarity NPC603503
0.5507 Remote Similarity NPC254741
0.5507 Remote Similarity NPC478987
0.5493 Remote Similarity NPC97716
0.5455 Remote Similarity NPC233502
0.5405 Remote Similarity NPC608710
0.5385 Remote Similarity NPC474264
0.5333 Remote Similarity NPC107838
0.5316 Remote Similarity NPC189270
0.5303 Remote Similarity NPC10467
0.525 Remote Similarity NPC187792
0.5224 Remote Similarity NPC181124
0.5224 Remote Similarity NPC121522
0.5211 Remote Similarity NPC606446
0.5152 Remote Similarity NPC185607
0.5139 Remote Similarity NPC600644
0.5132 Remote Similarity NPC184547
0.5077 Remote Similarity NPC223354
0.507 Remote Similarity NPC602496
0.5067 Remote Similarity NPC113055

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488135 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