Natural Product: NPC211759

Natural Product IDNPC211759
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JLJAVUZBHSLLJL-UPTANEPISA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102004935
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 JLJAVUZBHSLLJL-UPTANEPISA-N
Standard InCHI InChI=1S/C22H28O5/c1-13-14(2)22(16-8-10-18(24-4)20(12-16)26-6)27-21(13)15-7-9-17(23-3)19(11-15)25-5/h7-14,21-22H,1-6H3/t13-,14-,21-,22?/m1/s1
SMILES C[C@@H]1[C@@H](C)C(c2ccc(c(c2)OC)OC)O[C@H]1c1ccc(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.19 Volume:   391.531
?
Van der Waals volume.
Dense:   0.951 LogP:   2.526
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.816
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.365
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.728 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.194 Fsp3:   0.455
MCE-18:   61.75
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.204 Fluc inhibitor:   0.414
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.018
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.335 Promiscuous compounds:   0.092

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.953 MDCK Permeability:   -4.71
Pgp-inhibitor:   0.695 Pgp-substrate:   0.057
PAMPA:   0.007
?
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):   0.005
20% Bioavailability (F20%):   0.034 30% Bioavailability (F30%):   0.052
50% Bioavailability (F50%):   0.884

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.046 MRP1:   0.873
Plasma Protein Binding (PPB):   90.089% Volume Distribution (VD):   0.216
Fu: 7.883%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.976
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.56
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.07
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.98
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.1
CYP2D6-inhibitor:   0.054 CYP2D6-substrate:   0.988
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.162
?
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):  8.913 Half-life (T1/2):  2.226

ADMET: Toxicity

hERG Blockers:  0.222 hERG Blockers (10um):  0.561
Human Hepatotoxicity (H-HT):  0.551 Drug-induced Liver Injury (DILI):  0.652
AMES Toxicity:  0.54 Rat Oral Acute Toxicity:  0.328
Maximum Recommended Daily Dose:  0.333 Skin Sensitization:  0.2
Carcinogencity:  0.638 Eye Corrosion:  0.085
Eye Irritation:  0.809 Respiratory Toxicity:  0.763
Drug-induced Neurotoxicity:  0.76 Ototoxicity:  0.399
Hematotoxicity:  0.535 Drug-induced Nephrotoxicity:  0.397
Genotoxicity:  0.141 RPMI-8226 Immunitoxicity:  0.118
A549 Cytotoxicity:  0.167 Hek293 Cytotoxicity:  0.346
BCF:   2.381
?
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:   4.006
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.439
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.817
?
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
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[20476749]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. rhizome n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota Rhizomes n.a. n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota rhizomes n.a. n.a. PMID[22951040]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. rhizome n.a. PMID[23713285]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota rhizomes n.a. n.a. PMID[26296476]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[26305406]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota Rhizomes n.a. n.a. PMID[29116780]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[32807141]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. PMID[38821245]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8666 Acorus tatarinowii Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8666 Acorus tatarinowii Species Acoraceae 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

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 NPC211759 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 NPC216929
1.0 High Similarity NPC312713
1.0 High Similarity NPC126935
1.0 High Similarity NPC65933
1.0 High Similarity NPC57268
1.0 High Similarity NPC172676
0.8824 High Similarity NPC50683
0.8824 High Similarity NPC112571
0.8824 High Similarity NPC285725
0.8108 Intermediate Similarity NPC57119
0.8108 Intermediate Similarity NPC158471
0.8108 Intermediate Similarity NPC226862
0.7692 Intermediate Similarity NPC158331
0.75 Intermediate Similarity NPC136750
0.75 Intermediate Similarity NPC487684
0.75 Intermediate Similarity NPC266848
0.7317 Intermediate Similarity NPC11258
0.7317 Intermediate Similarity NPC21867
0.7317 Intermediate Similarity NPC45774
0.7317 Intermediate Similarity NPC74914
0.7027 Intermediate Similarity NPC271208
0.7027 Intermediate Similarity NPC233224
0.7027 Intermediate Similarity NPC610263
0.6765 Remote Similarity NPC9891
0.6765 Remote Similarity NPC88297
0.6765 Remote Similarity NPC186845
0.6667 Remote Similarity NPC260842
0.6667 Remote Similarity NPC93783
0.6667 Remote Similarity NPC320380
0.6316 Remote Similarity NPC121783
0.6316 Remote Similarity NPC34902
0.6316 Remote Similarity NPC18449
0.5957 Remote Similarity NPC135777
0.5957 Remote Similarity NPC7744
0.5833 Remote Similarity NPC142547
0.5833 Remote Similarity NPC228469
0.5833 Remote Similarity NPC488984
0.5833 Remote Similarity NPC488985
0.5769 Remote Similarity NPC302506
0.5769 Remote Similarity NPC241846
0.5769 Remote Similarity NPC93610
0.575 Remote Similarity NPC31530
0.5714 Remote Similarity NPC222127
0.5714 Remote Similarity NPC82862
0.5682 Remote Similarity NPC254120
0.561 Remote Similarity NPC282703
0.561 Remote Similarity NPC184733
0.561 Remote Similarity NPC72046
0.561 Remote Similarity NPC261812
0.561 Remote Similarity NPC128208
0.561 Remote Similarity NPC129570
0.561 Remote Similarity NPC65183
0.561 Remote Similarity NPC63238
0.561 Remote Similarity NPC602603
0.5581 Remote Similarity NPC606146
0.5577 Remote Similarity NPC179521
0.5556 Remote Similarity NPC487685
0.5476 Remote Similarity NPC204215
0.5455 Remote Similarity NPC470372
0.5435 Remote Similarity NPC487683
0.5333 Remote Similarity NPC227160
0.5333 Remote Similarity NPC82111
0.5333 Remote Similarity NPC483654
0.5273 Remote Similarity NPC77861
0.5217 Remote Similarity NPC488505
0.5208 Remote Similarity NPC488986
0.5143 Remote Similarity NPC258425
0.5111 Remote Similarity NPC175067

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC211759 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