Natural Product: NPC5310

Natural Product IDNPC5310
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3'-O-Demethylactigenin
IUPAC Name (3R,4R)-3-[(3,4-dihydroxyphenyl)methyl]-4-[(3,4-dimethoxyphenyl)methyl]oxolan-2-one
Synonyms 3'-O-Demethylactigenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL366800
PubChem CID 384870
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-epoxylignans
            • [CHEMONTID:0001613] Dibenzylbutyrolactone lignans

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 FTDOXLKYCKOSHA-LSDHHAIUSA-N
Standard InCHI InChI=1S/C20H22O6/c1-24-18-6-4-12(10-19(18)25-2)7-14-11-26-20(23)15(14)8-13-3-5-16(21)17(22)9-13/h3-6,9-10,14-15,21-22H,7-8,11H2,1-2H3/t14-,15+/m0/s1
SMILES COc1cc(ccc1OC)C[C@H]1COC(=O)[C@@H]1Cc1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.14 Volume:   363.093
?
Van der Waals volume.
Dense:   0.986 LogP:   1.754
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.004
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.586
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.61 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.112 Fsp3:   0.35
MCE-18:   58.0
?
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:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.278 Fluc inhibitor:   0.198
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.245
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.295 Promiscuous compounds:   0.295

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.082 MDCK Permeability:   -4.728
Pgp-inhibitor:   0.403 Pgp-substrate:   0.074
PAMPA:   0.04
?
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):   0.018
20% Bioavailability (F20%):   0.971 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.775
Plasma Protein Binding (PPB):   94.791% Volume Distribution (VD):   -0.532
Fu: 6.253%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.112
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.515
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.998
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.992
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.989
?
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):  11.049 Half-life (T1/2):  1.894

ADMET: Toxicity

hERG Blockers:  0.221 hERG Blockers (10um):  0.744
Human Hepatotoxicity (H-HT):  0.918 Drug-induced Liver Injury (DILI):  0.978
AMES Toxicity:  0.707 Rat Oral Acute Toxicity:  0.595
Maximum Recommended Daily Dose:  0.675 Skin Sensitization:  0.998
Carcinogencity:  0.578 Eye Corrosion:  0.012
Eye Irritation:  0.96 Respiratory Toxicity:  0.436
Drug-induced Neurotoxicity:  0.608 Ototoxicity:  0.845
Hematotoxicity:  0.501 Drug-induced Nephrotoxicity:  0.737
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.831 Hek293 Cytotoxicity:  0.535
BCF:   1.319
?
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:   4.107
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.327
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.929
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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
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28036 Distemonanthus benthamianus 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
NPT12 Individual protein Human immunodeficiency virus type 1 integrase Human immunodeficiency virus 1 Inhibition = 37.0 % PMID[8568830]
NPT12 Individual protein Human immunodeficiency virus type 1 integrase Human immunodeficiency virus 1 Inhibition = 52.0 % PMID[8568830]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT839 Cell line L6 Rattus norvegicus Activity = 243.2 % PMID[25941553]
NPT839 Cell line L6 Rattus norvegicus Activity = 238.9 % PMID[25941553]
NPT839 Cell line L6 Rattus norvegicus Ratio = 1.018 n.a. PMID[25941553]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 420.0 nM PMID[9834179]

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 NPC5310 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
0.7818 Intermediate Similarity NPC300776
0.7818 Intermediate Similarity NPC176814
0.7818 Intermediate Similarity NPC4982
0.7818 Intermediate Similarity NPC606629
0.7755 Intermediate Similarity NPC223807
0.717 Intermediate Similarity NPC211386
0.6984 Remote Similarity NPC478703
0.6984 Remote Similarity NPC478704
0.6786 Remote Similarity NPC205915
0.6727 Remote Similarity NPC68779
0.6727 Remote Similarity NPC108598
0.6613 Remote Similarity NPC282291
0.6613 Remote Similarity NPC166137
0.661 Remote Similarity NPC106920
0.661 Remote Similarity NPC15811
0.6308 Remote Similarity NPC478705
0.629 Remote Similarity NPC145569
0.6271 Remote Similarity NPC273657
0.6071 Remote Similarity NPC110958
0.6071 Remote Similarity NPC19890
0.6038 Remote Similarity NPC72796
0.6 Remote Similarity NPC176586
0.6 Remote Similarity NPC210354
0.6 Remote Similarity NPC216223
0.5902 Remote Similarity NPC191158
0.5902 Remote Similarity NPC177644
0.5818 Remote Similarity NPC325295
0.5818 Remote Similarity NPC76308
0.5758 Remote Similarity NPC174512
0.56 Remote Similarity NPC299706
0.56 Remote Similarity NPC245615
0.56 Remote Similarity NPC115466
0.56 Remote Similarity NPC61604
0.5571 Remote Similarity NPC158635
0.5571 Remote Similarity NPC229882
0.5469 Remote Similarity NPC293757
0.5469 Remote Similarity NPC668
0.5424 Remote Similarity NPC92693
0.5385 Remote Similarity NPC81067
0.5385 Remote Similarity NPC602945
0.5333 Remote Similarity NPC40237

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC5310 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