Natural Product: NPC262455

Natural Product IDNPC262455
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Austrobailignan-2
IUPAC Name (5R,5aS,8aR)-5-(7-methoxy-1,3-benzodioxol-5-yl)-5a,8,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-6-one
Synonyms Austrobailignan-2
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL455113
PubChem CID 10339853
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001510] Lignan lactones

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 GROYKMASYUMFER-GESALYCCSA-N
Standard InCHI InChI=1S/C21H18O7/c1-23-16-4-11(5-17-20(16)28-9-27-17)18-13-6-15-14(25-8-26-15)3-10(13)2-12-7-24-21(22)19(12)18/h3-6,12,18-19H,2,7-9H2,1H3/t12-,18+,19+/m0/s1
SMILES COc1cc(cc2c1OCO2)[C@H]1[C@@H]2C(=O)OC[C@@H]2Cc2c1cc1OCOc1c2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.11 Volume:   363.51
?
Van der Waals volume.
Dense:   1.051 LogP:   2.542
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.664
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.572
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   30.0
TPSA:   72.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   6.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.74 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.735 Fsp3:   0.381
MCE-18:   104.483
?
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:   0.507 Fluc inhibitor:   0.603
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.405
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.078
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.231 Promiscuous compounds:   0.464

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.948 MDCK Permeability:   -4.748
Pgp-inhibitor:   0.047 Pgp-substrate:   0.001
PAMPA:   0.06
?
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%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.003

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.998 MRP1:   0.954
Plasma Protein Binding (PPB):   97.307% Volume Distribution (VD):   0.134
Fu: 3.023%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.679
OATP1B3 inhibitor:   0.098 BCRP inhibitor:   0.0
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.92
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.987
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.002
HLM stability:   0.79
?
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):  3.007 Half-life (T1/2):  1.745

ADMET: Toxicity

hERG Blockers:  0.282 hERG Blockers (10um):  0.626
Human Hepatotoxicity (H-HT):  0.906 Drug-induced Liver Injury (DILI):  0.964
AMES Toxicity:  0.635 Rat Oral Acute Toxicity:  0.609
Maximum Recommended Daily Dose:  0.955 Skin Sensitization:  0.815
Carcinogencity:  0.835 Eye Corrosion:  0.0
Eye Irritation:  0.493 Respiratory Toxicity:  0.523
Drug-induced Neurotoxicity:  0.843 Ototoxicity:  0.767
Hematotoxicity:  0.84 Drug-induced Nephrotoxicity:  0.967
Genotoxicity:  0.984 RPMI-8226 Immunitoxicity:  0.263
A549 Cytotoxicity:  0.281 Hek293 Cytotoxicity:  0.59
BCF:   1.629
?
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:   4.176
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.572
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.4
?
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
NPO4224 Koelreuteria henryi Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[7714533]
NPO4224 Koelreuteria henryi Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4224 Koelreuteria henryi Species Sapindaceae 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
NPT762 Cell line A-431 Homo sapiens ED50 = 9.6 10'-1 ug/ml PMID[20413315]
NPT376 Cell line A498 Homo sapiens ED50 = 7.6 10'-1 ug/ml PMID[20392646]
NPT81 Cell line A549 Homo sapiens ED50 = 4.6 10'-1 ug/ml PMID[20392646]
NPT139 Cell line HT-29 Homo sapiens ED50 = 1.0 10'-1 ug/ml PMID[20392646]
NPT83 Cell line MCF7 Homo sapiens ED50 = 4.1 ug ml-1 PMID[20455578]
NPT306 Cell line PC-3 Homo sapiens ED50 = 3.1 ug ml-1 PMID[20398972]
NPT373 Cell line SK-MEL-5 Homo sapiens ED50 = 7.7 10'-1 ug/ml PMID[20398972]
NPT146 Cell line SK-OV-3 Homo sapiens ED50 = 8.32 10'-1 ug/ml PMID[16499327]
NPT2 Others Unspecified n.a. IC50 = 40000.0 nM PMID[16499327]
NPT2 Others Unspecified n.a. IC50 = 45000.0 nM PMID[16499327]

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 NPC262455 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 NPC177476
0.9423 High Similarity NPC80230
0.9423 High Similarity NPC104024
0.9423 High Similarity NPC101755
0.9423 High Similarity NPC304687
0.9423 High Similarity NPC65574
0.7857 Intermediate Similarity NPC218092
0.7857 Intermediate Similarity NPC246474
0.7857 Intermediate Similarity NPC162851
0.7797 Intermediate Similarity NPC30009
0.7797 Intermediate Similarity NPC103197
0.7759 Intermediate Similarity NPC480477
0.7458 Intermediate Similarity NPC149505
0.6712 Remote Similarity NPC115624
0.6615 Remote Similarity NPC115281
0.6207 Remote Similarity NPC23336
0.6129 Remote Similarity NPC239890
0.6129 Remote Similarity NPC209411
0.5846 Remote Similarity NPC237946
0.5846 Remote Similarity NPC32373
0.5797 Remote Similarity NPC163527
0.5763 Remote Similarity NPC92693
0.5738 Remote Similarity NPC164082
0.569 Remote Similarity NPC218841
0.5672 Remote Similarity NPC210642
0.5672 Remote Similarity NPC13985
0.5672 Remote Similarity NPC207584
0.5672 Remote Similarity NPC19947
0.5667 Remote Similarity NPC40237
0.5645 Remote Similarity NPC477698
0.5593 Remote Similarity NPC151423
0.5593 Remote Similarity NPC480480
0.5507 Remote Similarity NPC119910
0.55 Remote Similarity NPC222531
0.5469 Remote Similarity NPC191158
0.5469 Remote Similarity NPC177644
0.5333 Remote Similarity NPC193779
0.5254 Remote Similarity NPC11453
0.5246 Remote Similarity NPC475000
0.5211 Remote Similarity NPC288149
0.5211 Remote Similarity NPC470637
0.5077 Remote Similarity NPC176586
0.5077 Remote Similarity NPC210354
0.5075 Remote Similarity NPC293757
0.5075 Remote Similarity NPC668

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC262455 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
0.5846 Remote Similarity NPD4965 Approved
0.5846 Remote Similarity NPD4966 Phase 4
0.5846 Remote Similarity NPD4967 Phase 2

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