Natural Product: NPC310130

Natural Product IDNPC310130
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Lespeflorin A1
IUPAC Name (2S)-7-hydroxy-2-(4-methoxyphenyl)-6,8-bis(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms Lespeflorin A1
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL563314
PubChem CID 25243164
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 XGZTURSZEPLOKA-DEOSSOPVSA-N
Standard InCHI InChI=1S/C26H30O4/c1-16(2)6-8-19-14-22-23(27)15-24(18-9-11-20(29-5)12-10-18)30-26(22)21(25(19)28)13-7-17(3)4/h6-7,9-12,14,24,28H,8,13,15H2,1-5H3/t24-/m0/s1
SMILES COc1ccc(cc1)[C@@H]1CC(=O)c2c(O1)c(CC=C(C)C)c(c(c2)CC=C(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   406.21 Volume:   444.015
?
Van der Waals volume.
Dense:   0.915 LogP:   6.199
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.377
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.474
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   20.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.587 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.314 Fsp3:   0.346
MCE-18:   62.286
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.996 Fluc inhibitor:   0.879
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.676
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.547
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.409 Promiscuous compounds:   0.127

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.818 MDCK Permeability:   -4.668
Pgp-inhibitor:   0.978 Pgp-substrate:   0.009
PAMPA:   0.076
?
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):   0.182
20% Bioavailability (F20%):   0.993 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.866
Plasma Protein Binding (PPB):   96.091% Volume Distribution (VD):   0.335
Fu: 3.629%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.833
OATP1B3 inhibitor:   0.93 BCRP inhibitor:   0.999
BSEP inhibitor:   0.846

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.993 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.389 CYP2D6-substrate:   0.398
CYP3A4-inhibitor:   0.015 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):  9.128 Half-life (T1/2):  0.807

ADMET: Toxicity

hERG Blockers:  0.163 hERG Blockers (10um):  0.5
Human Hepatotoxicity (H-HT):  0.876 Drug-induced Liver Injury (DILI):  0.863
AMES Toxicity:  0.805 Rat Oral Acute Toxicity:  0.914
Maximum Recommended Daily Dose:  0.819 Skin Sensitization:  0.949
Carcinogencity:  0.391 Eye Corrosion:  0.0
Eye Irritation:  0.419 Respiratory Toxicity:  0.977
Drug-induced Neurotoxicity:  0.954 Ototoxicity:  0.752
Hematotoxicity:  0.542 Drug-induced Nephrotoxicity:  0.974
Genotoxicity:  0.984 RPMI-8226 Immunitoxicity:  0.138
A549 Cytotoxicity:  0.779 Hek293 Cytotoxicity:  0.522
BCF:   2.012
?
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:   5.324
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.411
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   7.008
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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
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota roots n.a. n.a. PMID[19132934]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. root n.a. PMID[19132934]
NPO13293 Lespedeza floribunda Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13293 Lespedeza floribunda 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
NPT2 Others Unspecified n.a. IC50 = 3960.0 nM PMID[22901896]

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 NPC310130 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
0.807 Intermediate Similarity NPC75049
0.7627 Intermediate Similarity NPC197252
0.7458 Intermediate Similarity NPC149026
0.6721 Remote Similarity NPC236766
0.6667 Remote Similarity NPC160821
0.6613 Remote Similarity NPC148757
0.619 Remote Similarity NPC150408
0.6032 Remote Similarity NPC164980
0.5846 Remote Similarity NPC250214
0.5606 Remote Similarity NPC265040
0.5588 Remote Similarity NPC608140
0.5538 Remote Similarity NPC143896
0.5538 Remote Similarity NPC169591
0.5538 Remote Similarity NPC298223
0.5538 Remote Similarity NPC604412
0.5507 Remote Similarity NPC161506
0.5455 Remote Similarity NPC91560
0.5455 Remote Similarity NPC39329
0.5455 Remote Similarity NPC51032
0.5441 Remote Similarity NPC76338
0.5441 Remote Similarity NPC250242
0.5373 Remote Similarity NPC69674
0.5362 Remote Similarity NPC293286
0.5362 Remote Similarity NPC291878
0.5333 Remote Similarity NPC284820
0.5303 Remote Similarity NPC76372
0.5303 Remote Similarity NPC37496
0.5294 Remote Similarity NPC68104
0.5294 Remote Similarity NPC66515
0.5294 Remote Similarity NPC480990
0.5294 Remote Similarity NPC35567
0.5294 Remote Similarity NPC610133
0.5224 Remote Similarity NPC107572
0.5224 Remote Similarity NPC32739
0.5211 Remote Similarity NPC473078
0.5147 Remote Similarity NPC187282
0.5139 Remote Similarity NPC36275
0.5135 Remote Similarity NPC477957
0.5132 Remote Similarity NPC192686
0.5132 Remote Similarity NPC101793
0.5079 Remote Similarity NPC296917
0.5079 Remote Similarity NPC170907
0.5075 Remote Similarity NPC258630
0.5072 Remote Similarity NPC220998
0.5068 Remote Similarity NPC246948
0.5067 Remote Similarity NPC479215
0.5067 Remote Similarity NPC477958

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC310130 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