Natural Product: NPC592419

Natural Product IDNPC592419
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isoanwulignan
IUPAC Name 5-[(2~{S},3~{S})-4-(1,3-benzodioxol-5-yl)-2,3-dimethyl-butyl]-2-methoxy-phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane 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 OLMIQOIPLQDJFU-KBPBESRZSA-N
Standard InCHI InChI=1S/C20H24O4/c1-13(8-15-4-6-18(22-3)17(21)10-15)14(2)9-16-5-7-19-20(11-16)24-12-23-19/h4-7,10-11,13-14,21H,8-9,12H2,1-3H3/t13-,14-/m0/s1
SMILES COC1=CC=C(C[C@H](C)[C@@H](C)CC2=CC=C3OCOC3=C2)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.17 Volume:   348.149
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Van der Waals volume.
Dense:   0.943 LogP:   3.732
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.436
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.462
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   16.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.864 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.946 Fsp3:   0.4
MCE-18:   52.214
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MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.597 Fluc inhibitor:   0.657
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.024
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.169
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.394 Promiscuous compounds:   0.439

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.875 MDCK Permeability:   -4.697
Pgp-inhibitor:   0.713 Pgp-substrate:   0.036
PAMPA:   0.017
?
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%):   0.087 30% Bioavailability (F30%):   0.117
50% Bioavailability (F50%):   0.95

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.19
Plasma Protein Binding (PPB):   96.935% Volume Distribution (VD):   -0.292
Fu: 3.048%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.561
OATP1B3 inhibitor:   0.454 BCRP inhibitor:   0.182
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.094 CYP1A2-substrate:   0.973
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.485 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.014 CYP2C8-inhibitor:   1.0
HLM stability:   0.997
?
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):  3.322 Half-life (T1/2):  1.023

ADMET: Toxicity

hERG Blockers:  0.334 hERG Blockers (10um):  0.701
Human Hepatotoxicity (H-HT):  0.693 Drug-induced Liver Injury (DILI):  0.767
AMES Toxicity:  0.634 Rat Oral Acute Toxicity:  0.253
Maximum Recommended Daily Dose:  0.343 Skin Sensitization:  0.729
Carcinogencity:  0.636 Eye Corrosion:  0.399
Eye Irritation:  0.984 Respiratory Toxicity:  0.511
Drug-induced Neurotoxicity:  0.691 Ototoxicity:  0.369
Hematotoxicity:  0.346 Drug-induced Nephrotoxicity:  0.669
Genotoxicity:  0.394 RPMI-8226 Immunitoxicity:  0.138
A549 Cytotoxicity:  0.341 Hek293 Cytotoxicity:  0.487
BCF:   2.254
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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:   4.428
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.773
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.151
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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
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. leaf n.a. PMID[16235962]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. stem n.a. PMID[16235962]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. root n.a. PMID[16394567]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. stem n.a. PMID[16394567]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[17970593]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[29595972]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[31556297]
NPO55807 Schisandra propinqua var.propinqua Genus Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30954 Kadsura longipedunculata Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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

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 NPC592419 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
0.7708 Intermediate Similarity NPC274356
0.7708 Intermediate Similarity NPC101748
0.7273 Intermediate Similarity NPC344161
0.7143 Intermediate Similarity NPC80241
0.7143 Intermediate Similarity NPC301641
0.7143 Intermediate Similarity NPC485483
0.6875 Remote Similarity NPC249788
0.66 Remote Similarity NPC485480
0.6545 Remote Similarity NPC487677
0.6545 Remote Similarity NPC487675
0.6545 Remote Similarity NPC46880
0.64 Remote Similarity NPC232275
0.6316 Remote Similarity NPC106739
0.6207 Remote Similarity NPC471505
0.6102 Remote Similarity NPC487679
0.6102 Remote Similarity NPC487678
0.6 Remote Similarity NPC227217
0.6 Remote Similarity NPC117780
0.5882 Remote Similarity NPC485482
0.5862 Remote Similarity NPC487681
0.5818 Remote Similarity NPC28398
0.5763 Remote Similarity NPC161249
0.5714 Remote Similarity NPC284464
0.5682 Remote Similarity NPC165106
0.566 Remote Similarity NPC104077
0.566 Remote Similarity NPC219671
0.566 Remote Similarity NPC147616
0.5625 Remote Similarity NPC470626
0.5625 Remote Similarity NPC40352
0.5625 Remote Similarity NPC213711
0.5577 Remote Similarity NPC196937
0.5536 Remote Similarity NPC135777
0.5532 Remote Similarity NPC76451
0.537 Remote Similarity NPC63574
0.5306 Remote Similarity NPC298757
0.5238 Remote Similarity NPC282291
0.5238 Remote Similarity NPC166137
0.5238 Remote Similarity NPC169973
0.5217 Remote Similarity NPC31279
0.5208 Remote Similarity NPC165133
0.5208 Remote Similarity NPC242885
0.5208 Remote Similarity NPC95614
0.5208 Remote Similarity NPC232316
0.5208 Remote Similarity NPC477886
0.5192 Remote Similarity NPC56214
0.5192 Remote Similarity NPC476748
0.5179 Remote Similarity NPC143895
0.5161 Remote Similarity NPC145569
0.5102 Remote Similarity NPC604144
0.5098 Remote Similarity NPC600801
0.5091 Remote Similarity NPC30951
0.5091 Remote Similarity NPC192255
0.5091 Remote Similarity NPC474288
0.5088 Remote Similarity NPC165128
0.5085 Remote Similarity NPC6369

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC592419 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
0.5682 Remote Similarity NPD5283 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