Natural Product: NPC7744

Natural Product IDNPC7744
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Futokadsurin C
IUPAC Name 5-[(2S,3R,4S,5S)-5-(2,3-dimethoxyphenyl)-3,4-dimethyloxolan-2-yl]-1,3-benzodioxole
Synonyms Futokadsurin C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL603427
PubChem CID 46228348
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-epoxylignans

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 LRAAAHJAYCYQAG-NXIGZUMLSA-N
Standard InCHI InChI=1S/C21H24O5/c1-12-13(2)20(15-6-5-7-17(22-3)21(15)23-4)26-19(12)14-8-9-16-18(10-14)25-11-24-16/h5-10,12-13,19-20H,11H2,1-4H3/t12-,13+,19+,20+/m1/s1
SMILES C[C@@H]1[C@H](C)[C@@H](c2cccc(c2OC)OC)O[C@@H]1c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.16 Volume:   365.679
?
Van der Waals volume.
Dense:   0.974 LogP:   3.04
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.113
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.599
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.806 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.508 Fsp3:   0.429
MCE-18:   73.333
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.469 Fluc inhibitor:   0.93
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.042
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.03
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.24 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.02 MDCK Permeability:   -4.729
Pgp-inhibitor:   0.58 Pgp-substrate:   0.012
PAMPA:   0.045
?
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):   0.0
20% Bioavailability (F20%):   0.029 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.631

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.994 MRP1:   0.984
Plasma Protein Binding (PPB):   97.841% Volume Distribution (VD):   0.106
Fu: 2.319%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.297
OATP1B3 inhibitor:   0.531 BCRP inhibitor:   0.02
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.854
CYP2C9-inhibitor:   0.136 CYP2C9-substrate:   0.969
CYP2D6-inhibitor:   0.852 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.012 CYP2C8-inhibitor:   0.097
HLM stability:   0.667
?
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):  6.316 Half-life (T1/2):  1.159

ADMET: Toxicity

hERG Blockers:  0.213 hERG Blockers (10um):  0.51
Human Hepatotoxicity (H-HT):  0.655 Drug-induced Liver Injury (DILI):  0.873
AMES Toxicity:  0.787 Rat Oral Acute Toxicity:  0.426
Maximum Recommended Daily Dose:  0.378 Skin Sensitization:  0.731
Carcinogencity:  0.838 Eye Corrosion:  0.072
Eye Irritation:  0.875 Respiratory Toxicity:  0.724
Drug-induced Neurotoxicity:  0.779 Ototoxicity:  0.285
Hematotoxicity:  0.638 Drug-induced Nephrotoxicity:  0.514
Genotoxicity:  0.6 RPMI-8226 Immunitoxicity:  0.177
A549 Cytotoxicity:  0.356 Hek293 Cytotoxicity:  0.498
BCF:   2.341
?
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:   3.888
?
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:   4.684
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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
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[11040054]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16724856]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[19900811]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. aerial part n.a. PMID[8237383]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[8237383]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[8368081]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4865 Piper kadsura Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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
NPT34 Cell line BV-2 Mus musculus Inhibition = 19.7 % PMID[19900811]
NPT34 Cell line BV-2 Mus musculus IC50 = 43100.0 nM PMID[19900811]

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 NPC7744 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
0.7447 Intermediate Similarity NPC57119
0.7447 Intermediate Similarity NPC158471
0.7447 Intermediate Similarity NPC226862
0.7333 Intermediate Similarity NPC271208
0.7333 Intermediate Similarity NPC233224
0.7333 Intermediate Similarity NPC610263
0.6364 Remote Similarity NPC135777
0.6346 Remote Similarity NPC487685
0.6346 Remote Similarity NPC136750
0.6346 Remote Similarity NPC266848
0.625 Remote Similarity NPC142547
0.625 Remote Similarity NPC228469
0.625 Remote Similarity NPC488984
0.625 Remote Similarity NPC488985
0.5957 Remote Similarity NPC216929
0.5957 Remote Similarity NPC312713
0.5957 Remote Similarity NPC126935
0.5957 Remote Similarity NPC65933
0.5957 Remote Similarity NPC57268
0.5957 Remote Similarity NPC172676
0.5738 Remote Similarity NPC179521
0.5645 Remote Similarity NPC302506
0.5645 Remote Similarity NPC241846
0.5645 Remote Similarity NPC93610
0.56 Remote Similarity NPC31530
0.5577 Remote Similarity NPC480478
0.549 Remote Similarity NPC50683
0.549 Remote Similarity NPC72046
0.549 Remote Similarity NPC261812
0.549 Remote Similarity NPC112571
0.549 Remote Similarity NPC65183
0.549 Remote Similarity NPC285725
0.5273 Remote Similarity NPC227160
0.5273 Remote Similarity NPC82111
0.5273 Remote Similarity NPC483654
0.5152 Remote Similarity NPC487682
0.5094 Remote Similarity NPC171928
0.5094 Remote Similarity NPC158526
0.5094 Remote Similarity NPC129687
0.5094 Remote Similarity NPC33611
0.5094 Remote Similarity NPC16830
0.5094 Remote Similarity NPC100223
0.5088 Remote Similarity NPC189474

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC7744 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