Natural Product: NPC125855

Natural Product IDNPC125855
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Macarangaflavanone B
IUPAC Name (2S)-5,7-dihydroxy-2-[4-hydroxy-3-(3-methylbut-2-enyl)phenyl]-6-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL471799
PubChem CID 14309760
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-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 WNEAAJKGMLICIY-QFIPXVFZSA-N
Standard InCHI InChI=1S/C25H28O5/c1-14(2)5-7-16-11-17(8-10-19(16)26)22-13-21(28)24-23(30-22)12-20(27)18(25(24)29)9-6-15(3)4/h5-6,8,10-12,22,26-27,29H,7,9,13H2,1-4H3/t22-/m0/s1
SMILES CC(=CCc1cc(ccc1O)[C@@H]1CC(=O)c2c(O1)cc(c(c2O)CC=C(C)C)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   408.19 Volume:   435.51
?
Van der Waals volume.
Dense:   0.937 LogP:   6.009
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.228
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.702
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.567 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.503 Fsp3:   0.32
MCE-18:   65.545
?
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:   0.967 Fluc inhibitor:   0.901
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.566
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.523
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.497 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.922 MDCK Permeability:   -4.704
Pgp-inhibitor:   0.747 Pgp-substrate:   0.007
PAMPA:   0.458
?
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):   0.069
20% Bioavailability (F20%):   0.949 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.893
Plasma Protein Binding (PPB):   94.947% Volume Distribution (VD):   0.361
Fu: 5.099%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.993
BSEP inhibitor:   0.8

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.329 CYP2D6-substrate:   0.651
CYP3A4-inhibitor:   0.029 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):  7.096 Half-life (T1/2):  1.076

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.548
Human Hepatotoxicity (H-HT):  0.797 Drug-induced Liver Injury (DILI):  0.803
AMES Toxicity:  0.846 Rat Oral Acute Toxicity:  0.934
Maximum Recommended Daily Dose:  0.702 Skin Sensitization:  0.99
Carcinogencity:  0.308 Eye Corrosion:  0.0
Eye Irritation:  0.675 Respiratory Toxicity:  0.996
Drug-induced Neurotoxicity:  0.78 Ototoxicity:  0.652
Hematotoxicity:  0.191 Drug-induced Nephrotoxicity:  0.963
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.222
A549 Cytotoxicity:  0.937 Hek293 Cytotoxicity:  0.799
BCF:   2.142
?
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:   5.063
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.69
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.028
?
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
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. fruit n.a. PMID[15787448]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. Madagascar rainforest n.a. PMID[15787448]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. root n.a. PMID[19132934]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota roots n.a. n.a. PMID[19132934]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21123068]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28522265]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[29641206]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1698 Glycyrrhiza inflata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1698 Glycyrrhiza inflata Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 90.0 % PMID[28522265]
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens IC50 = 1030.0 nM PMID[28522265]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT179 Cell line A2780 Homo sapiens IC50 = 16.0 ug.mL-1 PMID[23206866]
NPT83 Cell line MCF7 Homo sapiens GI = 36.0 % PMID[28522265]
NPT660 Cell line SW480 Homo sapiens GI = 87.0 % PMID[28522265]
NPT65 Cell line HepG2 Homo sapiens GI = 10.0 % PMID[28522265]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 5.0 % PMID[28522265]
NPT2 Others Unspecified n.a. IC50 = 2590.0 nM PMID[22037378]

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 NPC125855 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
0.8548 High Similarity NPC185276
0.7759 Intermediate Similarity NPC1089
0.75 Intermediate Similarity NPC109223
0.75 Intermediate Similarity NPC10937
0.746 Intermediate Similarity NPC35038
0.7377 Intermediate Similarity NPC166689
0.7258 Intermediate Similarity NPC608140
0.7097 Intermediate Similarity NPC223500
0.697 Remote Similarity NPC228504
0.6866 Remote Similarity NPC213896
0.6812 Remote Similarity NPC298692
0.6774 Remote Similarity NPC221432
0.6774 Remote Similarity NPC257097
0.6522 Remote Similarity NPC488556
0.6515 Remote Similarity NPC223787
0.6452 Remote Similarity NPC258630
0.6429 Remote Similarity NPC472627
0.6429 Remote Similarity NPC261063
0.6406 Remote Similarity NPC66515
0.6389 Remote Similarity NPC195796
0.6377 Remote Similarity NPC64915
0.6349 Remote Similarity NPC39329
0.6349 Remote Similarity NPC51032
0.6338 Remote Similarity NPC321779
0.6286 Remote Similarity NPC267375
0.625 Remote Similarity NPC472628
0.6232 Remote Similarity NPC290133
0.6154 Remote Similarity NPC197252
0.6111 Remote Similarity NPC226025
0.6111 Remote Similarity NPC278778
0.6094 Remote Similarity NPC150408
0.6081 Remote Similarity NPC27337
0.6056 Remote Similarity NPC470328
0.6056 Remote Similarity NPC209614
0.6056 Remote Similarity NPC164272
0.6056 Remote Similarity NPC470327
0.5946 Remote Similarity NPC210459
0.5938 Remote Similarity NPC143896
0.5921 Remote Similarity NPC474055
0.5915 Remote Similarity NPC472629
0.5844 Remote Similarity NPC472634
0.5844 Remote Similarity NPC293319
0.5821 Remote Similarity NPC106976
0.5797 Remote Similarity NPC470890
0.5758 Remote Similarity NPC69674
0.5758 Remote Similarity NPC265040
0.5733 Remote Similarity NPC45849
0.5733 Remote Similarity NPC472626
0.5733 Remote Similarity NPC488557
0.5676 Remote Similarity NPC488558
0.5672 Remote Similarity NPC220998
0.5672 Remote Similarity NPC610133
0.5634 Remote Similarity NPC39752
0.5606 Remote Similarity NPC236766
0.56 Remote Similarity NPC488554
0.56 Remote Similarity NPC472630
0.5571 Remote Similarity NPC200761
0.5538 Remote Similarity NPC197351
0.5526 Remote Similarity NPC472631
0.5522 Remote Similarity NPC171651
0.5507 Remote Similarity NPC189768
0.5484 Remote Similarity NPC482119
0.5484 Remote Similarity NPC482120
0.5484 Remote Similarity NPC324386
0.5455 Remote Similarity NPC472598
0.5441 Remote Similarity NPC17170
0.5385 Remote Similarity NPC488555
0.5385 Remote Similarity NPC484418
0.5373 Remote Similarity NPC13575
0.5352 Remote Similarity NPC138288
0.5333 Remote Similarity NPC58805
0.5294 Remote Similarity NPC95936
0.5224 Remote Similarity NPC169591
0.5224 Remote Similarity NPC298223
0.5224 Remote Similarity NPC604412
0.5147 Remote Similarity NPC107572
0.5147 Remote Similarity NPC32739
0.5143 Remote Similarity NPC285555
0.5143 Remote Similarity NPC76338
0.5143 Remote Similarity NPC250242
0.5139 Remote Similarity NPC291508
0.5079 Remote Similarity NPC312391
0.5072 Remote Similarity NPC187282
0.5072 Remote Similarity NPC75049
0.507 Remote Similarity NPC85121

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC125855 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