Natural Product: NPC204215

Natural Product IDNPC204215
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-(7S,8S,7'r,8'r)-4-Hydroxy-3,5,3',4',5'-Pentamethoxy-7,7'-Epoxylignan
IUPAC Name 4-[(2S,3S,4R,5R)-3,4-dimethyl-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]-2,6-dimethoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3105541
PubChem CID 76335614
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 BJMZZPKIBSAQBA-AHIIRKPMSA-N
Standard InCHI InChI=1S/C23H30O7/c1-12-13(2)22(15-10-18(27-5)23(29-7)19(11-15)28-6)30-21(12)14-8-16(25-3)20(24)17(9-14)26-4/h8-13,21-22,24H,1-7H3/t12-,13+,21-,22+/m0/s1
SMILES C[C@H]1[C@@H](C)[C@H](c2cc(c(c(c2)OC)OC)OC)O[C@@H]1c1cc(c(c(c1)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.2 Volume:   426.408
?
Van der Waals volume.
Dense:   0.981 LogP:   1.924
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.313
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.249
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   17.0
TPSA:   75.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.708 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.51 Fsp3:   0.478
MCE-18:   67.941
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.088 Fluc inhibitor:   0.331
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.031
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.066
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.316 Promiscuous compounds:   0.221

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.278 MDCK Permeability:   -4.855
Pgp-inhibitor:   0.551 Pgp-substrate:   0.049
PAMPA:   0.0
?
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%):   0.006 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.691

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.398 MRP1:   0.999
Plasma Protein Binding (PPB):   93.217% Volume Distribution (VD):   -0.169
Fu: 5.581%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.292
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.991 CYP1A2-substrate:   0.079
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.091
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.023
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.018
?
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):  7.486 Half-life (T1/2):  1.789

ADMET: Toxicity

hERG Blockers:  0.214 hERG Blockers (10um):  0.606
Human Hepatotoxicity (H-HT):  0.526 Drug-induced Liver Injury (DILI):  0.657
AMES Toxicity:  0.4 Rat Oral Acute Toxicity:  0.387
Maximum Recommended Daily Dose:  0.495 Skin Sensitization:  0.373
Carcinogencity:  0.635 Eye Corrosion:  0.035
Eye Irritation:  0.662 Respiratory Toxicity:  0.745
Drug-induced Neurotoxicity:  0.663 Ototoxicity:  0.429
Hematotoxicity:  0.645 Drug-induced Nephrotoxicity:  0.295
Genotoxicity:  0.086 RPMI-8226 Immunitoxicity:  0.218
A549 Cytotoxicity:  0.296 Hek293 Cytotoxicity:  0.567
BCF:   1.675
?
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:   3.847
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.402
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.627
?
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
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[10924192]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[11754613]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. root n.a. PMID[14750033]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[15482936]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota roots n.a. n.a. PMID[18841903]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Roots n.a. n.a. PMID[24359277]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota Aerial Parts n.a. n.a. PMID[24387347]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. PMID[31642320]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20323 Saururus chinensis Species Saururaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20323 Saururus chinensis Species Saururaceae 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
NPT164 Organism Human herpesvirus 4 Human herpesvirus 4 EC50 = 29500.0 nM PMID[19880317]
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 2.2 n.a. PMID[16643031]

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 NPC204215 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
0.7714 Intermediate Similarity NPC9891
0.7714 Intermediate Similarity NPC88297
0.7714 Intermediate Similarity NPC186845
0.7619 Intermediate Similarity NPC158331
0.7561 Intermediate Similarity NPC326095
0.6977 Remote Similarity NPC175067
0.6744 Remote Similarity NPC165155
0.6744 Remote Similarity NPC24490
0.6429 Remote Similarity NPC50683
0.6429 Remote Similarity NPC72046
0.6429 Remote Similarity NPC261812
0.6429 Remote Similarity NPC112571
0.6429 Remote Similarity NPC65183
0.6429 Remote Similarity NPC285725
0.6341 Remote Similarity NPC244983
0.619 Remote Similarity NPC31530
0.6047 Remote Similarity NPC282703
0.6047 Remote Similarity NPC184733
0.6047 Remote Similarity NPC128208
0.6047 Remote Similarity NPC129570
0.6047 Remote Similarity NPC63238
0.6047 Remote Similarity NPC602603
0.5849 Remote Similarity NPC477702
0.5833 Remote Similarity NPC11258
0.5833 Remote Similarity NPC21867
0.5833 Remote Similarity NPC45774
0.5833 Remote Similarity NPC74914
0.58 Remote Similarity NPC177868
0.5625 Remote Similarity NPC487684
0.56 Remote Similarity NPC185071
0.56 Remote Similarity NPC488986
0.5581 Remote Similarity NPC141765
0.5581 Remote Similarity NPC34103
0.5476 Remote Similarity NPC216929
0.5476 Remote Similarity NPC312713
0.5476 Remote Similarity NPC126935
0.5476 Remote Similarity NPC65933
0.5476 Remote Similarity NPC57268
0.5476 Remote Similarity NPC172676
0.5306 Remote Similarity NPC136750
0.5306 Remote Similarity NPC266848
0.5283 Remote Similarity NPC142547
0.5283 Remote Similarity NPC228469
0.5254 Remote Similarity NPC212890
0.52 Remote Similarity NPC487683
0.5094 Remote Similarity NPC135777

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC204215 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