Natural Product: NPC488984

Natural Product IDNPC488984
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RYXZHMFDFUHLJB-VTLGYEHRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101913976
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 RYXZHMFDFUHLJB-VTLGYEHRSA-N
Standard InCHI InChI=1S/C21H24O6/c1-11-12(2)20(14-7-15(22)21(24-4)18(9-14)23-3)27-19(11)13-5-6-16-17(8-13)26-10-25-16/h5-9,11-12,19-20,22H,10H2,1-4H3/t11-,12+,19-,20+/m1/s1
SMILES C[C@@H]1[C@H](C)[C@@H](c2cc(c(c(c2)OC)OC)O)O[C@H]1c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.16 Volume:   374.469
?
Van der Waals volume.
Dense:   0.994 LogP:   2.905
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.088
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.111
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.867 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.619 Fsp3:   0.429
MCE-18:   76.667
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.526 Fluc inhibitor:   0.783
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.128
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.226 Promiscuous compounds:   0.173

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.122 MDCK Permeability:   -4.775
Pgp-inhibitor:   0.078 Pgp-substrate:   0.004
PAMPA:   0.14
?
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%):   0.005 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.827

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.908 MRP1:   0.828
Plasma Protein Binding (PPB):   97.484% Volume Distribution (VD):   -0.137
Fu: 2.516%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.429
OATP1B3 inhibitor:   0.697 BCRP inhibitor:   0.021
BSEP inhibitor:   0.963

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.94
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.989
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.98
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.029
?
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):  5.025 Half-life (T1/2):  1.294

ADMET: Toxicity

hERG Blockers:  0.216 hERG Blockers (10um):  0.587
Human Hepatotoxicity (H-HT):  0.538 Drug-induced Liver Injury (DILI):  0.779
AMES Toxicity:  0.625 Rat Oral Acute Toxicity:  0.396
Maximum Recommended Daily Dose:  0.532 Skin Sensitization:  0.352
Carcinogencity:  0.764 Eye Corrosion:  0.032
Eye Irritation:  0.835 Respiratory Toxicity:  0.677
Drug-induced Neurotoxicity:  0.598 Ototoxicity:  0.404
Hematotoxicity:  0.53 Drug-induced Nephrotoxicity:  0.355
Genotoxicity:  0.468 RPMI-8226 Immunitoxicity:  0.155
A549 Cytotoxicity:  0.298 Hek293 Cytotoxicity:  0.597
BCF:   1.878
?
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:   3.859
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.804
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.755
?
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 = 19060.0 nM PMID[25116183]
NPT83 Cell line MCF7 Homo sapiens IC50 = 14020.0 nM PMID[25116183]
NPT81 Cell line A549 Homo sapiens IC50 = 27410.0 nM PMID[25116183]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 40000.0 nM PMID[25116183]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 39750.0 nM PMID[25116183]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 67.0 nM PMID[25116183]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 130.0 nM PMID[25116183]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 34.0 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 NPC488984 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 NPC488985
0.82 Intermediate Similarity NPC135777
0.7647 Intermediate Similarity NPC177868
0.7358 Intermediate Similarity NPC142547
0.7358 Intermediate Similarity NPC228469
0.7292 Intermediate Similarity NPC57119
0.7292 Intermediate Similarity NPC158471
0.7292 Intermediate Similarity NPC226862
0.7174 Intermediate Similarity NPC271208
0.7174 Intermediate Similarity NPC233224
0.7174 Intermediate Similarity NPC610263
0.68 Remote Similarity NPC175067
0.6792 Remote Similarity NPC488986
0.6538 Remote Similarity NPC487684
0.625 Remote Similarity NPC7744
0.6226 Remote Similarity NPC487685
0.6226 Remote Similarity NPC136750
0.6226 Remote Similarity NPC266848
0.6061 Remote Similarity NPC226153
0.6032 Remote Similarity NPC487682
0.5902 Remote Similarity NPC179521
0.5833 Remote Similarity NPC216929
0.5833 Remote Similarity NPC312713
0.5833 Remote Similarity NPC126935
0.5833 Remote Similarity NPC65933
0.5833 Remote Similarity NPC57268
0.5833 Remote Similarity NPC172676
0.5818 Remote Similarity NPC11258
0.5818 Remote Similarity NPC21867
0.5818 Remote Similarity NPC45774
0.5818 Remote Similarity NPC74914
0.5806 Remote Similarity NPC302506
0.5806 Remote Similarity NPC241846
0.5806 Remote Similarity NPC93610
0.5741 Remote Similarity NPC158331
0.5735 Remote Similarity NPC304048
0.5536 Remote Similarity NPC487683
0.549 Remote Similarity NPC31530
0.5472 Remote Similarity NPC480478
0.541 Remote Similarity NPC88640
0.541 Remote Similarity NPC101153
0.541 Remote Similarity NPC193666
0.541 Remote Similarity NPC123526
0.541 Remote Similarity NPC608725
0.5385 Remote Similarity NPC50683
0.5385 Remote Similarity NPC72046
0.5385 Remote Similarity NPC261812
0.5385 Remote Similarity NPC112571
0.5385 Remote Similarity NPC65183
0.5385 Remote Similarity NPC285725
0.5333 Remote Similarity NPC298317
0.5333 Remote Similarity NPC255566
0.5312 Remote Similarity NPC43514
0.5179 Remote Similarity NPC227160
0.5179 Remote Similarity NPC82111
0.5179 Remote Similarity NPC483654
0.5094 Remote Similarity NPC282703
0.5094 Remote Similarity NPC184733
0.5094 Remote Similarity NPC128208
0.5094 Remote Similarity NPC129570
0.5094 Remote Similarity NPC63238
0.5094 Remote Similarity NPC602603
0.5077 Remote Similarity NPC471505
0.5075 Remote Similarity NPC470372

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488984 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