Natural Product: NPC161506

Natural Product IDNPC161506
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-5,7-Dihydroxy-4'-Methoxy-8,3-Diprenylflavanone
IUPAC Name (2S)-5,7-dihydroxy-2-[4-methoxy-3-(3-methylbut-2-enyl)phenyl]-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL560530
PubChem CID 45268397
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 UJHSMBNEFBESCZ-DEOSSOPVSA-N
Standard InCHI InChI=1S/C26H30O5/c1-15(2)6-8-17-12-18(9-11-23(17)30-5)24-14-22(29)25-21(28)13-20(27)19(26(25)31-24)10-7-16(3)4/h6-7,9,11-13,24,27-28H,8,10,14H2,1-5H3/t24-/m0/s1
SMILES CC(=CCc1cc(ccc1OC)[C@@H]1CC(=O)c2c(cc(c(CC=C(C)C)c2O1)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.21 Volume:   452.806
?
Van der Waals volume.
Dense:   0.932 LogP:   6.072
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.175
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.534
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   20.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.573 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.449 Fsp3:   0.346
MCE-18:   65.4
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.989 Fluc inhibitor:   0.881
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.449
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.611
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.356 Promiscuous compounds:   0.164

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.803 MDCK Permeability:   -4.638
Pgp-inhibitor:   0.967 Pgp-substrate:   0.053
PAMPA:   0.046
?
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):   0.114
20% Bioavailability (F20%):   0.996 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.938
Plasma Protein Binding (PPB):   96.601% Volume Distribution (VD):   0.485
Fu: 3.087%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.975 BCRP inhibitor:   1.0
BSEP inhibitor:   0.685

ADMET: Metabolism

CYP1A2-inhibitor:   0.033 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.031
CYP2D6-inhibitor:   0.067 CYP2D6-substrate:   0.192
CYP3A4-inhibitor:   0.419 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):  6.201 Half-life (T1/2):  1.125

ADMET: Toxicity

hERG Blockers:  0.073 hERG Blockers (10um):  0.505
Human Hepatotoxicity (H-HT):  0.822 Drug-induced Liver Injury (DILI):  0.898
AMES Toxicity:  0.861 Rat Oral Acute Toxicity:  0.936
Maximum Recommended Daily Dose:  0.768 Skin Sensitization:  0.98
Carcinogencity:  0.559 Eye Corrosion:  0.0
Eye Irritation:  0.392 Respiratory Toxicity:  0.987
Drug-induced Neurotoxicity:  0.855 Ototoxicity:  0.698
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.964
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.174
A549 Cytotoxicity:  0.89 Hek293 Cytotoxicity:  0.712
BCF:   2.282
?
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:   5.311
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.149
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.621
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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
NPO32948 propolis Genus Rhytismataceae Eukaryota n.a. n.a. n.a. PMID[10757720]
NPO32948 propolis Genus Rhytismataceae Eukaryota n.a. n.a. n.a. PMID[1593279]
NPO32948 propolis Genus Rhytismataceae Eukaryota n.a. China n.a. PMID[19278239]
NPO32948 propolis Genus Rhytismataceae Eukaryota n.a. Ywar Taw village, Shan State of Myanmar 2006-Dec PMID[19572611]
NPO32948 propolis Genus Rhytismataceae 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
NPT461 Cell line PANC-1 Homo sapiens CD100 = 12.5 uM PMID[19666224]
NPT461 Cell line PANC-1 Homo sapiens PC50 = 7.9 uM PMID[19572611]

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 NPC161506 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
0.7966 Intermediate Similarity NPC148757
0.7581 Intermediate Similarity NPC291878
0.7541 Intermediate Similarity NPC66515
0.75 Intermediate Similarity NPC107572
0.75 Intermediate Similarity NPC32739
0.7333 Intermediate Similarity NPC76372
0.7333 Intermediate Similarity NPC37496
0.7258 Intermediate Similarity NPC480990
0.6935 Remote Similarity NPC324436
0.6935 Remote Similarity NPC78
0.6667 Remote Similarity NPC36217
0.6667 Remote Similarity NPC306829
0.6515 Remote Similarity NPC485610
0.6515 Remote Similarity NPC182852
0.6462 Remote Similarity NPC17170
0.6377 Remote Similarity NPC166934
0.6232 Remote Similarity NPC24136
0.6176 Remote Similarity NPC10990
0.6143 Remote Similarity NPC300988
0.597 Remote Similarity NPC220998
0.5882 Remote Similarity NPC76338
0.5882 Remote Similarity NPC250242
0.5821 Remote Similarity NPC149026
0.5821 Remote Similarity NPC250214
0.5797 Remote Similarity NPC608140
0.5735 Remote Similarity NPC109223
0.5735 Remote Similarity NPC10937
0.5672 Remote Similarity NPC150408
0.5614 Remote Similarity NPC28918
0.56 Remote Similarity NPC227579
0.56 Remote Similarity NPC214166
0.5588 Remote Similarity NPC187282
0.5588 Remote Similarity NPC69674
0.5588 Remote Similarity NPC265040
0.5522 Remote Similarity NPC164980
0.5522 Remote Similarity NPC258630
0.5522 Remote Similarity NPC480991
0.5513 Remote Similarity NPC484417
0.5507 Remote Similarity NPC68104
0.5507 Remote Similarity NPC310130
0.5441 Remote Similarity NPC236766
0.5429 Remote Similarity NPC285555
0.5417 Remote Similarity NPC200761
0.5405 Remote Similarity NPC474021
0.5385 Remote Similarity NPC218226
0.5333 Remote Similarity NPC477957
0.5325 Remote Similarity NPC107177
0.5325 Remote Similarity NPC485612
0.5325 Remote Similarity NPC101793
0.5294 Remote Similarity NPC169591
0.5294 Remote Similarity NPC298223
0.5294 Remote Similarity NPC604412
0.5286 Remote Similarity NPC197252
0.5286 Remote Similarity NPC610133
0.5278 Remote Similarity NPC485620
0.5263 Remote Similarity NPC477958
0.5217 Remote Similarity NPC91560
0.5211 Remote Similarity NPC106976
0.5205 Remote Similarity NPC473078
0.5143 Remote Similarity NPC262038
0.5143 Remote Similarity NPC319910
0.5143 Remote Similarity NPC75049
0.5143 Remote Similarity NPC156190
0.5139 Remote Similarity NPC278476
0.5135 Remote Similarity NPC278249
0.5135 Remote Similarity NPC223812
0.5128 Remote Similarity NPC111786
0.5063 Remote Similarity NPC474023
0.5063 Remote Similarity NPC132592

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC161506 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