Natural Product: NPC265154

Natural Product IDNPC265154
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kobusin
IUPAC Name 4-[(3S,3aR,6S,6aR)-6-(4-methyl-1,3-benzodioxol-5-yl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-3-yl]-2-methoxyphenol
Synonyms Kobusin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462823
PubChem CID 44559453
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 OFCHTGCBFRTISG-VUEDXXQZSA-N
Standard InCHI InChI=1S/C21H22O6/c1-11-13(4-6-17-19(11)27-10-26-17)21-15-9-24-20(14(15)8-25-21)12-3-5-16(22)18(7-12)23-2/h3-7,14-15,20-22H,8-10H2,1-2H3/t14-,15-,20+,21+/m0/s1
SMILES Cc1c(ccc2c1OCO2)[C@@H]1[C@H]2CO[C@H](c3ccc(c(c3)OC)O)[C@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.14 Volume:   365.912
?
Van der Waals volume.
Dense:   1.012 LogP:   2.32
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.36
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.635
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   25.0
TPSA:   66.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.892 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.983 Fsp3:   0.429
MCE-18:   90.133
?
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:   0.631 Fluc inhibitor:   0.701
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.068
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.091
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.152 Promiscuous compounds:   0.181

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.061 MDCK Permeability:   -4.722
Pgp-inhibitor:   0.301 Pgp-substrate:   0.036
PAMPA:   0.004
?
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%):   0.014 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.639

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.88 MRP1:   0.978
Plasma Protein Binding (PPB):   96.553% Volume Distribution (VD):   -0.158
Fu: 3.498%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.981 BCRP inhibitor:   0.057
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.987
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.748
CYP2C9-inhibitor:   0.814 CYP2C9-substrate:   0.985
CYP2D6-inhibitor:   0.989 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.993 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.006
HLM stability:   0.518
?
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):  7.53 Half-life (T1/2):  1.273

ADMET: Toxicity

hERG Blockers:  0.091 hERG Blockers (10um):  0.414
Human Hepatotoxicity (H-HT):  0.735 Drug-induced Liver Injury (DILI):  0.904
AMES Toxicity:  0.839 Rat Oral Acute Toxicity:  0.316
Maximum Recommended Daily Dose:  0.314 Skin Sensitization:  0.942
Carcinogencity:  0.728 Eye Corrosion:  0.026
Eye Irritation:  0.974 Respiratory Toxicity:  0.432
Drug-induced Neurotoxicity:  0.398 Ototoxicity:  0.302
Hematotoxicity:  0.424 Drug-induced Nephrotoxicity:  0.684
Genotoxicity:  0.826 RPMI-8226 Immunitoxicity:  0.171
A549 Cytotoxicity:  0.249 Hek293 Cytotoxicity:  0.403
BCF:   1.545
?
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:   3.935
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.334
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.701
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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
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[12608853]
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[32239935]
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10821 Magnolia praecocissima Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10821 Magnolia praecocissima Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10821 Magnolia praecocissima Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10821 Magnolia praecocissima Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae 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
NPT2 Others Unspecified n.a. IC50 = 7400.0 nM PMID[12608853]

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 NPC265154 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
0.7586 Intermediate Similarity NPC88640
0.7586 Intermediate Similarity NPC101153
0.7586 Intermediate Similarity NPC193666
0.7586 Intermediate Similarity NPC123526
0.7586 Intermediate Similarity NPC608725
0.7414 Intermediate Similarity NPC474139
0.6724 Remote Similarity NPC27843
0.6724 Remote Similarity NPC7171
0.6667 Remote Similarity NPC115207
0.6667 Remote Similarity NPC158079
0.6667 Remote Similarity NPC228346
0.6667 Remote Similarity NPC40432
0.6667 Remote Similarity NPC161557
0.6207 Remote Similarity NPC126409
0.6207 Remote Similarity NPC99572
0.6129 Remote Similarity NPC298317
0.6129 Remote Similarity NPC255566
0.5625 Remote Similarity NPC142547
0.5625 Remote Similarity NPC228469
0.5571 Remote Similarity NPC487682
0.55 Remote Similarity NPC227160
0.55 Remote Similarity NPC82111
0.5469 Remote Similarity NPC223185
0.5469 Remote Similarity NPC610778
0.5397 Remote Similarity NPC185071
0.5397 Remote Similarity NPC478955
0.5397 Remote Similarity NPC478700
0.5362 Remote Similarity NPC471505
0.5345 Remote Similarity NPC171928
0.5345 Remote Similarity NPC158526
0.5345 Remote Similarity NPC129687
0.5345 Remote Similarity NPC33611
0.5345 Remote Similarity NPC16830
0.5345 Remote Similarity NPC100223
0.5323 Remote Similarity NPC189474
0.5205 Remote Similarity NPC470097
0.5065 Remote Similarity NPC324492
0.5065 Remote Similarity NPC38041
0.5065 Remote Similarity NPC22150
0.5065 Remote Similarity NPC317053

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC265154 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