Natural Product: NPC153739

Natural Product IDNPC153739
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+)-Neoolivil
IUPAC Name 4-[(2R,3S,4S,5R)-5-(4-hydroxy-3-methoxyphenyl)-3,4-bis(hydroxymethyl)oxolan-2-yl]-2-methoxyphenol
Synonyms (+)-Neo-Olivil; (+)-Neoolivil
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464631
PubChem CID 9976812
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 NYDZRKZVFLLTLO-NSMLZSOPSA-N
Standard InCHI InChI=1S/C20H24O7/c1-25-17-7-11(3-5-15(17)23)19-13(9-21)14(10-22)20(27-19)12-4-6-16(24)18(8-12)26-2/h3-8,13-14,19-24H,9-10H2,1-2H3/t13-,14-,19+,20+/m1/s1
SMILES OC[C@H]1[C@@H](O[C@H]([C@@H]1CO)c1ccc(c(c1)OC)O)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   376.15 Volume:   374.52
?
Van der Waals volume.
Dense:   1.004 LogP:   0.715
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.09
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.124
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   108.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.612 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.674 Fsp3:   0.4
MCE-18:   62.429
?
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:   0.377 Fluc inhibitor:   0.351
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.107
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.304 Promiscuous compounds:   0.388

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.856 MDCK Permeability:   -5.283
Pgp-inhibitor:   0.165 Pgp-substrate:   0.209
PAMPA:   0.051
?
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):   0.011
20% Bioavailability (F20%):   0.237 30% Bioavailability (F30%):   0.395
50% Bioavailability (F50%):   0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.841
Plasma Protein Binding (PPB):   76.265% Volume Distribution (VD):   -0.124
Fu: 25.256%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.7
BSEP inhibitor:   0.273

ADMET: Metabolism

CYP1A2-inhibitor:   0.994 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.053
CYP3A4-inhibitor:   0.052 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.0
?
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):  8.352 Half-life (T1/2):  1.965

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.254
Human Hepatotoxicity (H-HT):  0.725 Drug-induced Liver Injury (DILI):  0.534
AMES Toxicity:  0.785 Rat Oral Acute Toxicity:  0.172
Maximum Recommended Daily Dose:  0.134 Skin Sensitization:  0.983
Carcinogencity:  0.563 Eye Corrosion:  0.021
Eye Irritation:  0.956 Respiratory Toxicity:  0.393
Drug-induced Neurotoxicity:  0.273 Ototoxicity:  0.543
Hematotoxicity:  0.326 Drug-induced Nephrotoxicity:  0.512
Genotoxicity:  0.558 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.422 Hek293 Cytotoxicity:  0.377
BCF:   0.595
?
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:   2.961
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.367
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.514
?
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
NPO28843 Astragalus zahlbruckneri Species Fabaceae Eukaryota Roots n.a. n.a. PMID[11575952]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota stem bark Kunming, Yunnan Province, China n.a. PMID[18986199]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. PMID[36447306]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. PMID[39696148]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29397 Thymus longiflorus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23017 Urtica dioica Species Urticaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29397 Thymus longiflorus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28843 Astragalus zahlbruckneri Species Fabaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 > 300000.0 nM PMID[18986199]

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 NPC153739 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 NPC242807
0.75 Intermediate Similarity NPC282703
0.75 Intermediate Similarity NPC184733
0.75 Intermediate Similarity NPC128208
0.75 Intermediate Similarity NPC129570
0.75 Intermediate Similarity NPC63238
0.75 Intermediate Similarity NPC602603
0.7 Intermediate Similarity NPC244983
0.6809 Remote Similarity NPC478955
0.6809 Remote Similarity NPC478700
0.6383 Remote Similarity NPC11258
0.6383 Remote Similarity NPC21867
0.6383 Remote Similarity NPC487683
0.6383 Remote Similarity NPC45774
0.6383 Remote Similarity NPC74914
0.6364 Remote Similarity NPC115207
0.6364 Remote Similarity NPC158079
0.6364 Remote Similarity NPC228346
0.6364 Remote Similarity NPC40432
0.6364 Remote Similarity NPC142985
0.6364 Remote Similarity NPC161557
0.6304 Remote Similarity NPC147379
0.6222 Remote Similarity NPC326095
0.6154 Remote Similarity NPC272
0.6154 Remote Similarity NPC187998
0.6154 Remote Similarity NPC77040
0.6154 Remote Similarity NPC257582
0.6154 Remote Similarity NPC241522
0.6154 Remote Similarity NPC485398
0.6136 Remote Similarity NPC209567
0.6122 Remote Similarity NPC488986
0.6038 Remote Similarity NPC610652
0.5957 Remote Similarity NPC469480
0.5926 Remote Similarity NPC282833
0.5833 Remote Similarity NPC126409
0.5833 Remote Similarity NPC99572
0.5769 Remote Similarity NPC142547
0.5769 Remote Similarity NPC228469
0.5741 Remote Similarity NPC277804
0.5741 Remote Similarity NPC481088
0.5625 Remote Similarity NPC470804
0.5532 Remote Similarity NPC4940
0.549 Remote Similarity NPC27843
0.549 Remote Similarity NPC7171
0.5472 Remote Similarity NPC181049
0.5439 Remote Similarity NPC42300
0.5424 Remote Similarity NPC287745
0.5357 Remote Similarity NPC486558
0.5333 Remote Similarity NPC85488
0.5333 Remote Similarity NPC476343
0.5283 Remote Similarity NPC223185
0.5283 Remote Similarity NPC610778
0.5254 Remote Similarity NPC77861
0.5246 Remote Similarity NPC476840
0.5246 Remote Similarity NPC476842
0.5106 Remote Similarity NPC480479
0.5106 Remote Similarity NPC280704
0.5091 Remote Similarity NPC471942
0.5085 Remote Similarity NPC64201

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC153739 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