Natural Product: NPC85895

Natural Product IDNPC85895
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Confluentin
IUPAC Name (2R)-2-[(3E)-4,8-dimethylnona-3,7-dienyl]-2,7-dimethylchromen-5-ol
Synonyms Confluentin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL449069
PubChem CID 10381750
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001549] Monoterpenoids
          • [CHEMONTID:0001564] Bicyclic monoterpenoids

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 WQOSNKWCIQZRGH-IHSQGBLNSA-N
Standard InCHI InChI=1S/C22H30O2/c1-16(2)8-6-9-17(3)10-7-12-22(5)13-11-19-20(23)14-18(4)15-21(19)24-22/h8,10-11,13-15,23H,6-7,9,12H2,1-5H3/b17-10+/t22-/m1/s1
SMILES C/C(=CCC[C@]1(C)C=Cc2c(O1)cc(cc2O)C)/CCC=C(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.22 Volume:   373.717
?
Van der Waals volume.
Dense:   0.873 LogP:   6.623
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.408
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.01
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   29.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.618 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.569 Fsp3:   0.455
MCE-18:   45.938
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.871 Fluc inhibitor:   0.016
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.338
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.331
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.729 Promiscuous compounds:   0.165

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.867 MDCK Permeability:   -4.746
Pgp-inhibitor:   0.995 Pgp-substrate:   0.001
PAMPA:   0.007
?
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):   0.0
20% Bioavailability (F20%):   0.065 30% Bioavailability (F30%):   0.075
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.056 MRP1:   0.993
Plasma Protein Binding (PPB):   96.307% Volume Distribution (VD):   0.133
Fu: 3.264%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.005
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.991
CYP2C19-inhibitor:   0.523 CYP2C19-substrate:   0.848
CYP2C9-inhibitor:   0.462 CYP2C9-substrate:   0.736
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.793
CYP3A4-inhibitor:   0.822 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.998
?
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):  9.255 Half-life (T1/2):  0.657

ADMET: Toxicity

hERG Blockers:  0.201 hERG Blockers (10um):  0.707
Human Hepatotoxicity (H-HT):  0.703 Drug-induced Liver Injury (DILI):  0.086
AMES Toxicity:  0.33 Rat Oral Acute Toxicity:  0.275
Maximum Recommended Daily Dose:  0.388 Skin Sensitization:  0.977
Carcinogencity:  0.269 Eye Corrosion:  0.049
Eye Irritation:  0.925 Respiratory Toxicity:  0.936
Drug-induced Neurotoxicity:  0.473 Ototoxicity:  0.399
Hematotoxicity:  0.214 Drug-induced Nephrotoxicity:  0.526
Genotoxicity:  0.094 RPMI-8226 Immunitoxicity:  0.151
A549 Cytotoxicity:  0.302 Hek293 Cytotoxicity:  0.325
BCF:   2.319
?
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:   5.166
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.543
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.222
?
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
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. whole plant n.a. DOI[10.1007/BF02329610]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. PMID[15270561]
NPO10941 Albatrellus ovinus Species Albatrellaceae Eukaryota n.a. n.a. n.a. PMID[23305465]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10941 Albatrellus ovinus Species Albatrellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10941 Albatrellus ovinus Species Albatrellaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10941 Albatrellus ovinus Species Albatrellaceae 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
NPT83 Cell line MCF7 Homo sapiens IC50 = 23010.0 nM PMID[23305465]
NPT81 Cell line A549 Homo sapiens IC50 = 18480.0 nM PMID[23305465]
NPT116 Cell line HL-60 Homo sapiens IC50 = 15050.0 nM PMID[23305465]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 17080.0 nM PMID[23305465]
NPT2 Others Unspecified n.a. IC50 = 205.0 uL PMID[15270561]

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 NPC85895 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
0.8545 High Similarity NPC212965
0.7759 Intermediate Similarity NPC120638
0.7288 Intermediate Similarity NPC137294
0.7167 Intermediate Similarity NPC131397
0.6667 Remote Similarity NPC37139
0.6667 Remote Similarity NPC607595
0.661 Remote Similarity NPC476006
0.65 Remote Similarity NPC233059
0.65 Remote Similarity NPC74137
0.65 Remote Similarity NPC218753
0.65 Remote Similarity NPC601175
0.6129 Remote Similarity NPC474481
0.6032 Remote Similarity NPC82503
0.6032 Remote Similarity NPC478288
0.5758 Remote Similarity NPC600342
0.5714 Remote Similarity NPC488436
0.5634 Remote Similarity NPC488435
0.5417 Remote Similarity NPC601888
0.5417 Remote Similarity NPC610065
0.5362 Remote Similarity NPC241976
0.5342 Remote Similarity NPC604977
0.5333 Remote Similarity NPC474920
0.5303 Remote Similarity NPC601185
0.5303 Remote Similarity NPC604281
0.5231 Remote Similarity NPC474616
0.5224 Remote Similarity NPC485470
0.5167 Remote Similarity NPC473718
0.5161 Remote Similarity NPC479913
0.5147 Remote Similarity NPC483636
0.5143 Remote Similarity NPC471587
0.5139 Remote Similarity NPC608840
0.5068 Remote Similarity NPC608841
0.5063 Remote Similarity NPC227906

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC85895 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