Natural Product: NPC324436

Natural Product IDNPC324436
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+/-)Leachianone G
IUPAC Name 2-(2,4-dihydroxyphenyl)-5,7-dihydroxy-8-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms (+/-)-Leachianone G
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1783937
PubChem CID 11810419
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 VBOYLFNGTSLAAZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H20O6/c1-10(2)3-5-13-15(23)8-16(24)19-17(25)9-18(26-20(13)19)12-6-4-11(21)7-14(12)22/h3-4,6-8,18,21-24H,5,9H2,1-2H3
SMILES CC(=CCC1=C2C(=C(C=C1O)O)C(=O)CC(O2)C3=C(C=C(C=C3)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   360.456
?
Van der Waals volume.
Dense:   0.988 LogP:   3.317
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.081
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.15
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.624 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.388 Fsp3:   0.25
MCE-18:   63.2
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.857 Fluc inhibitor:   0.577
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.778
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.563
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.402 Promiscuous compounds:   0.025

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.157 MDCK Permeability:   -4.814
Pgp-inhibitor:   0.544 Pgp-substrate:   0.08
PAMPA:   0.088
?
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):   0.01
20% Bioavailability (F20%):   0.862 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.956
Plasma Protein Binding (PPB):   93.965% Volume Distribution (VD):   0.592
Fu: 6.247%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.994
BSEP inhibitor:   0.261

ADMET: Metabolism

CYP1A2-inhibitor:   0.667 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.848 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.838 CYP2C9-substrate:   0.917
CYP2D6-inhibitor:   0.97 CYP2D6-substrate:   0.721
CYP3A4-inhibitor:   0.004 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):  2.45 Half-life (T1/2):  1.884

ADMET: Toxicity

hERG Blockers:  0.05 hERG Blockers (10um):  0.575
Human Hepatotoxicity (H-HT):  0.647 Drug-induced Liver Injury (DILI):  0.327
AMES Toxicity:  0.709 Rat Oral Acute Toxicity:  0.818
Maximum Recommended Daily Dose:  0.699 Skin Sensitization:  0.948
Carcinogencity:  0.479 Eye Corrosion:  0.0
Eye Irritation:  0.948 Respiratory Toxicity:  0.942
Drug-induced Neurotoxicity:  0.182 Ototoxicity:  0.431
Hematotoxicity:  0.076 Drug-induced Nephrotoxicity:  0.524
Genotoxicity:  0.986 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.676 Hek293 Cytotoxicity:  0.902
BCF:   1.711
?
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:   4.534
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.807
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.162
?
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
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10654410]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[10843587]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[15568770]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16392664]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota roots Hualien Hsien, Taiwan 2003-JUL PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[17951038]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18175961]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20815207]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. bark n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[22207282]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[23806866]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24295087]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. Konya, Turkey 2007-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota root bark University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic 2011-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota leaves Chungbuk, Korea n.a. PMID[25935644]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[25981820]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. latex n.a. PMID[27294120]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27575476]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[30298740]
NPO28265 Morus alba Species Moraceae Eukaryota Root barks n.a. n.a. PMID[3097265]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[9868163]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. Database[Article]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19231 Sophora flavescens 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT681 Cell line PC-12 Rattus norvegicus Activity = 94.8 % PMID[19442520]
NPT177 Tissue Aorta Rattus norvegicus EC50 = 9300.0 nM PMID[19442520]
NPT177 Tissue Aorta Rattus norvegicus Emax = 94.9 % PMID[19442520]

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 NPC324436 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
1.0 High Similarity NPC78
0.8182 Intermediate Similarity NPC107572
0.8182 Intermediate Similarity NPC306829
0.8182 Intermediate Similarity NPC32739
0.7759 Intermediate Similarity NPC285555
0.7544 Intermediate Similarity NPC91560
0.75 Intermediate Similarity NPC485620
0.7368 Intermediate Similarity NPC76372
0.7368 Intermediate Similarity NPC37496
0.7333 Intermediate Similarity NPC485610
0.7333 Intermediate Similarity NPC182852
0.7288 Intermediate Similarity NPC66515
0.7258 Intermediate Similarity NPC278249
0.7258 Intermediate Similarity NPC223812
0.7213 Intermediate Similarity NPC10990
0.7143 Intermediate Similarity NPC300988
0.7119 Intermediate Similarity NPC148757
0.6935 Remote Similarity NPC161506
0.6923 Remote Similarity NPC485617
0.6875 Remote Similarity NPC166934
0.6774 Remote Similarity NPC291878
0.6769 Remote Similarity NPC328164
0.6721 Remote Similarity NPC480990
0.6667 Remote Similarity NPC36217
0.6615 Remote Similarity NPC131579
0.6615 Remote Similarity NPC485613
0.6613 Remote Similarity NPC223500
0.6567 Remote Similarity NPC214774
0.6441 Remote Similarity NPC103420
0.6232 Remote Similarity NPC195621
0.6212 Remote Similarity NPC24136
0.6032 Remote Similarity NPC265040
0.597 Remote Similarity NPC81697
0.597 Remote Similarity NPC485615
0.5968 Remote Similarity NPC164980
0.5968 Remote Similarity NPC480991
0.5965 Remote Similarity NPC295261
0.5965 Remote Similarity NPC296490
0.5942 Remote Similarity NPC473016
0.5781 Remote Similarity NPC262038
0.5781 Remote Similarity NPC319910
0.5694 Remote Similarity NPC609256
0.5692 Remote Similarity NPC220998
0.5658 Remote Similarity NPC301256
0.5606 Remote Similarity NPC76338
0.5606 Remote Similarity NPC250242
0.5593 Remote Similarity NPC4743
0.5588 Remote Similarity NPC473078
0.5556 Remote Similarity NPC28918
0.5541 Remote Similarity NPC218226
0.5538 Remote Similarity NPC187282
0.5538 Remote Similarity NPC102540
0.5538 Remote Similarity NPC75049
0.5522 Remote Similarity NPC608140
0.5507 Remote Similarity NPC473015
0.5479 Remote Similarity NPC107177
0.5479 Remote Similarity NPC485612
0.5455 Remote Similarity NPC109223
0.5455 Remote Similarity NPC10937
0.5455 Remote Similarity NPC610133
0.5429 Remote Similarity NPC131568
0.5424 Remote Similarity NPC603284
0.5385 Remote Similarity NPC236766
0.5385 Remote Similarity NPC150408
0.5362 Remote Similarity NPC85162
0.5323 Remote Similarity NPC310135
0.5312 Remote Similarity NPC477244
0.5303 Remote Similarity NPC149026
0.5303 Remote Similarity NPC69674
0.5303 Remote Similarity NPC250214
0.5294 Remote Similarity NPC278476
0.5238 Remote Similarity NPC246648
0.5231 Remote Similarity NPC258630
0.5224 Remote Similarity NPC17170
0.5224 Remote Similarity NPC197252
0.5217 Remote Similarity NPC470647
0.5211 Remote Similarity NPC246948
0.5205 Remote Similarity NPC77794
0.5205 Remote Similarity NPC225660
0.5167 Remote Similarity NPC472460
0.5147 Remote Similarity NPC166689
0.5139 Remote Similarity NPC96408
0.5139 Remote Similarity NPC610511
0.507 Remote Similarity NPC36275
0.5068 Remote Similarity NPC216035
0.5065 Remote Similarity NPC484417

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC324436 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