Natural Product: NPC246648

Natural Product IDNPC246648
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-7,4'-Dihydroxy-8-Prenylflavan
IUPAC Name (2S)-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)-3,4-dihydro-2H-chromen-7-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1951405
PubChem CID 57402293
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans

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 LMDXLPTZCSMMDJ-IBGZPJMESA-N
Standard InCHI InChI=1S/C20H22O3/c1-13(2)3-10-17-18(22)11-6-15-7-12-19(23-20(15)17)14-4-8-16(21)9-5-14/h3-6,8-9,11,19,21-22H,7,10,12H2,1-2H3/t19-/m0/s1
SMILES CC(=CCc1c(ccc2CC[C@@H](c3ccc(cc3)O)Oc12)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   310.16 Volume:   336.722
?
Van der Waals volume.
Dense:   0.921 LogP:   3.925
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.444
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.667
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   49.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.81 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.039 Fsp3:   0.3
MCE-18:   54.923
?
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:   0.928 Fluc inhibitor:   0.86
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.062
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.239
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.489 Promiscuous compounds:   0.056

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.791 MDCK Permeability:   -4.737
Pgp-inhibitor:   0.276 Pgp-substrate:   0.476
PAMPA:   0.022
?
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%):   0.782 30% Bioavailability (F30%):   0.978
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.974
Plasma Protein Binding (PPB):   93.931% Volume Distribution (VD):   0.422
Fu: 6.912%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.529
OATP1B3 inhibitor:   0.477 BCRP inhibitor:   0.987
BSEP inhibitor:   0.92

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.97 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.191 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.883 CYP2D6-substrate:   0.22
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  9.684 Half-life (T1/2):  1.19

ADMET: Toxicity

hERG Blockers:  0.359 hERG Blockers (10um):  0.654
Human Hepatotoxicity (H-HT):  0.822 Drug-induced Liver Injury (DILI):  0.297
AMES Toxicity:  0.446 Rat Oral Acute Toxicity:  0.797
Maximum Recommended Daily Dose:  0.859 Skin Sensitization:  0.962
Carcinogencity:  0.14 Eye Corrosion:  0.001
Eye Irritation:  0.736 Respiratory Toxicity:  0.966
Drug-induced Neurotoxicity:  0.876 Ototoxicity:  0.59
Hematotoxicity:  0.089 Drug-induced Nephrotoxicity:  0.772
Genotoxicity:  0.867 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.71 Hek293 Cytotoxicity:  0.73
BCF:   1.75
?
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:   4.959
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.945
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.575
?
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
NPO5877 Morus yunnanensis Species Moraceae Eukaryota n.a. n.a. n.a. PMID[22165973]
NPO19617 Crateva religiosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5877 Morus yunnanensis Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21070 Dendrosicyos socotrana Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19617 Crateva religiosa Species Capparaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5877 Morus yunnanensis Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18059 Acacia orites Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21676 Heracleum pastinacifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22808 Hesperocyparis stephensonii Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20337 Ageratina pichinchensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19617 Crateva religiosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21070 Dendrosicyos socotrana Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19771 Pterocephalus plumosus Species Caprifoliaceae 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 < 50.0 % PMID[22165973]

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 NPC246648 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
0.7885 Intermediate Similarity NPC103420
0.6842 Remote Similarity NPC285040
0.68 Remote Similarity NPC106914
0.68 Remote Similarity NPC86502
0.6667 Remote Similarity NPC164980
0.6271 Remote Similarity NPC107572
0.6271 Remote Similarity NPC32739
0.6207 Remote Similarity NPC197351
0.5735 Remote Similarity NPC479215
0.5714 Remote Similarity NPC76338
0.5714 Remote Similarity NPC250242
0.5606 Remote Similarity NPC36275
0.5484 Remote Similarity NPC91560
0.5484 Remote Similarity NPC150408
0.5472 Remote Similarity NPC93398
0.5472 Remote Similarity NPC258979
0.5472 Remote Similarity NPC8283
0.5439 Remote Similarity NPC134195
0.5397 Remote Similarity NPC149026
0.5397 Remote Similarity NPC265040
0.5397 Remote Similarity NPC75049
0.5312 Remote Similarity NPC66515
0.5294 Remote Similarity NPC166934
0.5238 Remote Similarity NPC324436
0.5238 Remote Similarity NPC78
0.5238 Remote Similarity NPC236766
0.5238 Remote Similarity NPC149796
0.5217 Remote Similarity NPC479211
0.5156 Remote Similarity NPC473413
0.5156 Remote Similarity NPC262038
0.5156 Remote Similarity NPC319910
0.5143 Remote Similarity NPC479213
0.5085 Remote Similarity NPC17809
0.5079 Remote Similarity NPC76372
0.5079 Remote Similarity NPC37496
0.5079 Remote Similarity NPC482704
0.5077 Remote Similarity NPC220998

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC246648 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