Natural Product: NPC488986

Natural Product IDNPC488986
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IEXPORSGDXJAPE-UAFHBQARSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 118711165
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 IEXPORSGDXJAPE-UAFHBQARSA-N
Standard InCHI InChI=1S/C21H26O6/c1-11-12(2)20(14-8-16(23)21(26-5)18(10-14)25-4)27-19(11)13-6-7-15(22)17(9-13)24-3/h6-12,19-20,22-23H,1-5H3/t11-,12-,19+,20-/m0/s1
SMILES C[C@H]1[C@H](C)[C@@H](c2cc(c(c(c2)OC)OC)O)O[C@H]1c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.17 Volume:   383.025
?
Van der Waals volume.
Dense:   0.977 LogP:   2.087
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.285
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.645
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   17.0
TPSA:   77.38
?
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:   0.816 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.566 Fsp3:   0.429
MCE-18:   65.333
?
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:   0
Colloidal aggregators:   0.215 Fluc inhibitor:   0.365
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.03
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.083
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.322 Promiscuous compounds:   0.239

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.224 MDCK Permeability:   -4.834
Pgp-inhibitor:   0.153 Pgp-substrate:   0.146
PAMPA:   0.122
?
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):   0.008
20% Bioavailability (F20%):   0.333 30% Bioavailability (F30%):   0.204
50% Bioavailability (F50%):   0.924

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.134 MRP1:   0.976
Plasma Protein Binding (PPB):   86.276% Volume Distribution (VD):   -0.236
Fu: 14.04%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.455
BSEP inhibitor:   0.298

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.138
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.496
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.001
?
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):  7.813 Half-life (T1/2):  1.395

ADMET: Toxicity

hERG Blockers:  0.147 hERG Blockers (10um):  0.49
Human Hepatotoxicity (H-HT):  0.765 Drug-induced Liver Injury (DILI):  0.779
AMES Toxicity:  0.54 Rat Oral Acute Toxicity:  0.42
Maximum Recommended Daily Dose:  0.324 Skin Sensitization:  0.798
Carcinogencity:  0.513 Eye Corrosion:  0.081
Eye Irritation:  0.887 Respiratory Toxicity:  0.862
Drug-induced Neurotoxicity:  0.433 Ototoxicity:  0.381
Hematotoxicity:  0.466 Drug-induced Nephrotoxicity:  0.42
Genotoxicity:  0.624 RPMI-8226 Immunitoxicity:  0.235
A549 Cytotoxicity:  0.699 Hek293 Cytotoxicity:  0.561
BCF:   1.077
?
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:   3.448
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.918
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.129
?
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
NPO7118 Manglietiastrum sinicum Species Magnoliaceae Eukaryota Mature Carpels n.a. n.a. PMID[25116183]
NPO7118 Manglietiastrum sinicum Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7118 Manglietiastrum sinicum 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
NPT660 Cell line SW480 Homo sapiens IC50 > 40000.0 nM PMID[25116183]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[25116183]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[25116183]
NPT65 Cell line HepG2 Homo sapiens IC50 = 3150.0 nM PMID[30448414]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 40000.0 nM PMID[25116183]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 130.0 nM PMID[25116183]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 67.0 nM PMID[25116183]

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 NPC488986 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
0.7907 Intermediate Similarity NPC282703
0.7907 Intermediate Similarity NPC184733
0.7907 Intermediate Similarity NPC128208
0.7907 Intermediate Similarity NPC129570
0.7907 Intermediate Similarity NPC63238
0.7907 Intermediate Similarity NPC602603
0.75 Intermediate Similarity NPC11258
0.75 Intermediate Similarity NPC21867
0.75 Intermediate Similarity NPC487683
0.75 Intermediate Similarity NPC45774
0.75 Intermediate Similarity NPC74914
0.7234 Intermediate Similarity NPC175067
0.6792 Remote Similarity NPC142547
0.6792 Remote Similarity NPC228469
0.6792 Remote Similarity NPC488984
0.6792 Remote Similarity NPC488985
0.6415 Remote Similarity NPC177868
0.6275 Remote Similarity NPC487684
0.6122 Remote Similarity NPC242807
0.6122 Remote Similarity NPC153739
0.5902 Remote Similarity NPC77861
0.58 Remote Similarity NPC142985
0.5769 Remote Similarity NPC147379
0.5769 Remote Similarity NPC158331
0.5714 Remote Similarity NPC135777
0.56 Remote Similarity NPC204215
0.5556 Remote Similarity NPC487682
0.549 Remote Similarity NPC115207
0.549 Remote Similarity NPC158079
0.549 Remote Similarity NPC228346
0.549 Remote Similarity NPC40432
0.549 Remote Similarity NPC161557
0.5472 Remote Similarity NPC469480
0.5357 Remote Similarity NPC27843
0.5357 Remote Similarity NPC7171
0.5208 Remote Similarity NPC216929
0.5208 Remote Similarity NPC312713
0.5208 Remote Similarity NPC126935
0.5208 Remote Similarity NPC65933
0.5208 Remote Similarity NPC57268
0.5208 Remote Similarity NPC172676
0.5091 Remote Similarity NPC126409
0.5091 Remote Similarity NPC99572

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488986 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