Natural Product: NPC21867

Natural Product IDNPC21867
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Nectandrin A
IUPAC Name 4-[(2S,3S,4R,5R)-5-(3,4-dimethoxyphenyl)-3,4-dimethyloxolan-2-yl]-2-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL444025
PubChem CID 13939326
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 YPQNDHHCUQGPFN-WVGOSAFVSA-N
Standard InCHI InChI=1S/C21H26O5/c1-12-13(2)21(15-7-9-17(23-3)19(11-15)25-5)26-20(12)14-6-8-16(22)18(10-14)24-4/h6-13,20-22H,1-5H3/t12-,13+,20-,21+/m0/s1
SMILES C[C@H]1[C@@H](C)[C@H](c2ccc(c(c2)OC)OC)O[C@@H]1c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.18 Volume:   374.235
?
Van der Waals volume.
Dense:   0.957 LogP:   2.334
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.641
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.48
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   17.0
TPSA:   57.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.853 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.309 Fsp3:   0.429
MCE-18:   62.067
?
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:   0.286 Fluc inhibitor:   0.372
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.024
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.017
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.329 Promiscuous compounds:   0.248

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.196 MDCK Permeability:   -4.768
Pgp-inhibitor:   0.293 Pgp-substrate:   0.068
PAMPA:   0.005
?
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%):   0.029 30% Bioavailability (F30%):   0.094
50% Bioavailability (F50%):   0.945

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.919
Plasma Protein Binding (PPB):   94.044% Volume Distribution (VD):   0.069
Fu: 4.862%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.926
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.524
BSEP inhibitor:   0.926

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.071
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.964
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.269
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.013
?
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):  9.383 Half-life (T1/2):  1.798

ADMET: Toxicity

hERG Blockers:  0.195 hERG Blockers (10um):  0.597
Human Hepatotoxicity (H-HT):  0.472 Drug-induced Liver Injury (DILI):  0.525
AMES Toxicity:  0.644 Rat Oral Acute Toxicity:  0.36
Maximum Recommended Daily Dose:  0.381 Skin Sensitization:  0.45
Carcinogencity:  0.586 Eye Corrosion:  0.144
Eye Irritation:  0.929 Respiratory Toxicity:  0.704
Drug-induced Neurotoxicity:  0.588 Ototoxicity:  0.365
Hematotoxicity:  0.416 Drug-induced Nephrotoxicity:  0.311
Genotoxicity:  0.266 RPMI-8226 Immunitoxicity:  0.111
A549 Cytotoxicity:  0.224 Hek293 Cytotoxicity:  0.537
BCF:   1.395
?
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:   3.809
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.275
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.582
?
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
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[14738383]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[15324487]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota seeds n.a. n.a. PMID[17998162]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[1955885]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. fruit n.a. PMID[20879744]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. leaf n.a. PMID[26184150]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[27419473]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[32515616]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[33444950]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19004 Dryobalanops camphora Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19078 Lophocolea bidentata Species Lophocoleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Aril n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3739 Nectandra megapotamica Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19004 Dryobalanops camphora Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19078 Lophocolea bidentata Species Lophocoleaceae 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
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 10.2 % PMID[14738383]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 13.5 % PMID[14738383]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Activity = 18.0 % PMID[14738383]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 17407000.0 nM PMID[14738383]

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 NPC21867 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 NPC11258
1.0 High Similarity NPC45774
1.0 High Similarity NPC74914
0.8293 Intermediate Similarity NPC282703
0.8293 Intermediate Similarity NPC184733
0.8293 Intermediate Similarity NPC128208
0.8293 Intermediate Similarity NPC129570
0.8293 Intermediate Similarity NPC63238
0.8293 Intermediate Similarity NPC602603
0.8125 Intermediate Similarity NPC142547
0.8125 Intermediate Similarity NPC228469
0.7826 Intermediate Similarity NPC487683
0.7778 Intermediate Similarity NPC158331
0.7609 Intermediate Similarity NPC487684
0.75 Intermediate Similarity NPC488986
0.7317 Intermediate Similarity NPC216929
0.7317 Intermediate Similarity NPC312713
0.7317 Intermediate Similarity NPC126935
0.7317 Intermediate Similarity NPC65933
0.7317 Intermediate Similarity NPC57268
0.7317 Intermediate Similarity NPC172676
0.7273 Intermediate Similarity NPC77861
0.7143 Intermediate Similarity NPC27843
0.7143 Intermediate Similarity NPC7171
0.6667 Remote Similarity NPC50683
0.6667 Remote Similarity NPC112571
0.6667 Remote Similarity NPC285725
0.6552 Remote Similarity NPC487682
0.6383 Remote Similarity NPC242807
0.6383 Remote Similarity NPC142985
0.6383 Remote Similarity NPC153739
0.625 Remote Similarity NPC57119
0.625 Remote Similarity NPC158471
0.625 Remote Similarity NPC226862
0.6226 Remote Similarity NPC135777
0.6 Remote Similarity NPC147379
0.6 Remote Similarity NPC469480
0.5938 Remote Similarity NPC304048
0.5893 Remote Similarity NPC88640
0.5893 Remote Similarity NPC101153
0.5893 Remote Similarity NPC193666
0.5893 Remote Similarity NPC123526
0.5893 Remote Similarity NPC608725
0.5882 Remote Similarity NPC136750
0.5882 Remote Similarity NPC266848
0.5833 Remote Similarity NPC204215
0.5818 Remote Similarity NPC488984
0.5818 Remote Similarity NPC488985
0.5738 Remote Similarity NPC470372
0.5714 Remote Similarity NPC115207
0.5714 Remote Similarity NPC158079
0.5714 Remote Similarity NPC228346
0.5714 Remote Similarity NPC40432
0.5714 Remote Similarity NPC161557
0.5636 Remote Similarity NPC260842
0.5636 Remote Similarity NPC93783
0.5636 Remote Similarity NPC320380
0.55 Remote Similarity NPC471505
0.55 Remote Similarity NPC43514
0.5417 Remote Similarity NPC271208
0.5417 Remote Similarity NPC233224
0.5417 Remote Similarity NPC610263
0.541 Remote Similarity NPC64201
0.5283 Remote Similarity NPC126409
0.5283 Remote Similarity NPC99572
0.5263 Remote Similarity NPC488988
0.5192 Remote Similarity NPC175067
0.5192 Remote Similarity NPC227217
0.5192 Remote Similarity NPC117780
0.5111 Remote Similarity NPC9891
0.5111 Remote Similarity NPC88297
0.5111 Remote Similarity NPC186845
0.5088 Remote Similarity NPC223185
0.5088 Remote Similarity NPC610778
0.5075 Remote Similarity NPC226153

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC21867 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