Natural Product: NPC102781

Natural Product IDNPC102781
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AWOGQCSIVCQXBT-PBFVBANWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12697524
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid 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 AWOGQCSIVCQXBT-PBFVBANWSA-N
Standard InCHI InChI=1S/C21H22O6/c1-22-16-5-3-12(7-18(16)23-2)20-14-9-25-21(15(14)10-24-20)13-4-6-17-19(8-13)27-11-26-17/h3-8,14-15,20-21H,9-11H2,1-2H3/t14-,15-,20-,21-/m0/s1
SMILES COc1ccc(cc1OC)[C@H]1[C@H]2CO[C@@H](c3ccc4c(c3)OCO4)[C@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.14 Volume:   365.912
?
Van der Waals volume.
Dense:   1.012 LogP:   1.831
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.128
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.992
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   25.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.821 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.629 Fsp3:   0.429
MCE-18:   86.667
?
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:   0.47 Fluc inhibitor:   0.827
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.043
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.04
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.278 Promiscuous compounds:   0.307

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.871 MDCK Permeability:   -4.819
Pgp-inhibitor:   0.328 Pgp-substrate:   0.097
PAMPA:   0.019
?
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%):   0.061 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.701

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.271 MRP1:   0.834
Plasma Protein Binding (PPB):   94.178% Volume Distribution (VD):   0.203
Fu: 6.763%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.963
OATP1B3 inhibitor:   0.955 BCRP inhibitor:   0.111
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.93
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.403
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.15 CYP2C8-inhibitor:   0.005
HLM stability:   0.424
?
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):  5.796 Half-life (T1/2):  1.9

ADMET: Toxicity

hERG Blockers:  0.168 hERG Blockers (10um):  0.405
Human Hepatotoxicity (H-HT):  0.749 Drug-induced Liver Injury (DILI):  0.954
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.308
Maximum Recommended Daily Dose:  0.334 Skin Sensitization:  0.698
Carcinogencity:  0.825 Eye Corrosion:  0.056
Eye Irritation:  0.943 Respiratory Toxicity:  0.466
Drug-induced Neurotoxicity:  0.604 Ototoxicity:  0.322
Hematotoxicity:  0.585 Drug-induced Nephrotoxicity:  0.574
Genotoxicity:  0.788 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.194 Hek293 Cytotoxicity:  0.324
BCF:   2.013
?
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:   3.866
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.537
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.804
?
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
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. flower bud n.a. PMID[17628872]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[19370929]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[22080044]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. flower bud n.a. PMID[7779269]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25197 Magnolia sprengeri Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1918 Magnolia kobus Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15064 Magnolia denudata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18811 Magnolia biondii Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15294 Magnolia salicifolia Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25197 Magnolia sprengeri Species Magnoliaceae 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 NPC102781 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 NPC227160
1.0 High Similarity NPC82111
0.8974 High Similarity NPC171928
0.8974 High Similarity NPC158526
0.8974 High Similarity NPC129687
0.8974 High Similarity NPC33611
0.8974 High Similarity NPC16830
0.8974 High Similarity NPC100223
0.8605 High Similarity NPC189474
0.8205 Intermediate Similarity NPC121783
0.8205 Intermediate Similarity NPC34902
0.8205 Intermediate Similarity NPC18449
0.7708 Intermediate Similarity NPC298317
0.7708 Intermediate Similarity NPC255566
0.7551 Intermediate Similarity NPC474139
0.7551 Intermediate Similarity NPC483653
0.7442 Intermediate Similarity NPC222127
0.7442 Intermediate Similarity NPC82862
0.74 Intermediate Similarity NPC88640
0.74 Intermediate Similarity NPC101153
0.74 Intermediate Similarity NPC193666
0.74 Intermediate Similarity NPC123526
0.74 Intermediate Similarity NPC608725
0.6889 Remote Similarity NPC57119
0.6889 Remote Similarity NPC158471
0.6889 Remote Similarity NPC226862
0.6889 Remote Similarity NPC606146
0.6735 Remote Similarity NPC14022
0.6735 Remote Similarity NPC601703
0.6667 Remote Similarity NPC148893
0.6667 Remote Similarity NPC25333
0.6667 Remote Similarity NPC49235
0.6596 Remote Similarity NPC483654
0.6471 Remote Similarity NPC469981
0.64 Remote Similarity NPC27843
0.64 Remote Similarity NPC7171
0.625 Remote Similarity NPC600032
0.6122 Remote Similarity NPC488505
0.6042 Remote Similarity NPC312199
0.6 Remote Similarity NPC271208
0.6 Remote Similarity NPC233224
0.6 Remote Similarity NPC610263
0.5965 Remote Similarity NPC311057
0.5814 Remote Similarity NPC281864
0.5814 Remote Similarity NPC328682
0.5814 Remote Similarity NPC54321
0.58 Remote Similarity NPC136750
0.58 Remote Similarity NPC266848
0.5769 Remote Similarity NPC185071
0.5741 Remote Similarity NPC24257
0.5741 Remote Similarity NPC153620
0.5667 Remote Similarity NPC308555
0.5625 Remote Similarity NPC480478
0.5536 Remote Similarity NPC47181
0.55 Remote Similarity NPC265154
0.5455 Remote Similarity NPC101807
0.537 Remote Similarity NPC165128
0.5342 Remote Similarity NPC486663
0.5333 Remote Similarity NPC216929
0.5333 Remote Similarity NPC312713
0.5333 Remote Similarity NPC126935
0.5333 Remote Similarity NPC65933
0.5333 Remote Similarity NPC57268
0.5333 Remote Similarity NPC172676
0.5286 Remote Similarity NPC486098
0.5273 Remote Similarity NPC135777
0.5273 Remote Similarity NPC7744
0.5263 Remote Similarity NPC12728
0.5246 Remote Similarity NPC246947
0.5208 Remote Similarity NPC473092
0.5208 Remote Similarity NPC473093
0.5208 Remote Similarity NPC8050
0.52 Remote Similarity NPC137487
0.5192 Remote Similarity NPC487685
0.5179 Remote Similarity NPC142547
0.5179 Remote Similarity NPC228469
0.5179 Remote Similarity NPC488984
0.5179 Remote Similarity NPC488985
0.5167 Remote Similarity NPC302506
0.5167 Remote Similarity NPC241846
0.5167 Remote Similarity NPC93610
0.5161 Remote Similarity NPC487682
0.5082 Remote Similarity NPC276753
0.5082 Remote Similarity NPC205796
0.507 Remote Similarity NPC186316

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC102781 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