Natural Product: NPC158737

Natural Product IDNPC158737
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Alpha-Methylcubebin
IUPAC Name 5-[[(2R,3R,4R)-4-(1,3-benzodioxol-5-ylmethyl)-2-methoxyoxolan-3-yl]methyl]-1,3-benzodioxole
Synonyms Alpha-Methylcubebin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL520915
PubChem CID 44575384
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-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 UUUXPUGZNDRYSV-GCKMJXCFSA-N
Standard InCHI InChI=1S/C21H22O6/c1-22-21-16(7-14-3-5-18-20(9-14)27-12-25-18)15(10-23-21)6-13-2-4-17-19(8-13)26-11-24-17/h2-5,8-9,15-16,21H,6-7,10-12H2,1H3/t15-,16+,21+/m0/s1
SMILES CO[C@@H]1OC[C@@H]([C@H]1Cc1ccc2c(c1)OCO2)Cc1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.14 Volume:   365.912
?
Van der Waals volume.
Dense:   1.012 LogP:   2.595
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.614
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.231
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   25.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.806 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.578 Fsp3:   0.429
MCE-18:   81.6
?
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:   0.506 Fluc inhibitor:   0.517
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.115
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.273 Promiscuous compounds:   0.096

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.943 MDCK Permeability:   -4.719
Pgp-inhibitor:   0.929 Pgp-substrate:   0.021
PAMPA:   0.172
?
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%):   0.034 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.248

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.979 MRP1:   0.707
Plasma Protein Binding (PPB):   98.04% Volume Distribution (VD):   0.335
Fu: 2.322%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.953
OATP1B3 inhibitor:   0.812 BCRP inhibitor:   0.005
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.958
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.982
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.732 CYP3A4-substrate:   1.0
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.783
?
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):  4.132 Half-life (T1/2):  0.804

ADMET: Toxicity

hERG Blockers:  0.34 hERG Blockers (10um):  0.483
Human Hepatotoxicity (H-HT):  0.944 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.941 Rat Oral Acute Toxicity:  0.343
Maximum Recommended Daily Dose:  0.405 Skin Sensitization:  0.835
Carcinogencity:  0.712 Eye Corrosion:  0.002
Eye Irritation:  0.933 Respiratory Toxicity:  0.506
Drug-induced Neurotoxicity:  0.944 Ototoxicity:  0.661
Hematotoxicity:  0.594 Drug-induced Nephrotoxicity:  0.899
Genotoxicity:  0.991 RPMI-8226 Immunitoxicity:  0.254
A549 Cytotoxicity:  0.534 Hek293 Cytotoxicity:  0.592
BCF:   2.115
?
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:   4.229
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.958
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.271
?
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
NPO8246 Lantana involucrata Species Verbenaceae Eukaryota n.a. n.a. n.a. PMID[15217280]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[15568798]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[15679319]
NPO4890 Streptomyces rimosus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[17631493]
NPO13607 Arenaria kansuensis Species Scolopacidae Eukaryota n.a. n.a. n.a. PMID[17655145]
NPO4890 Streptomyces rimosus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[1833366]
NPO9032 Geotrichum candidum Species Dipodascaceae Eukaryota n.a. n.a. n.a. PMID[20488699]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. fruit n.a. PMID[22396124]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[31096694]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO9032 Geotrichum candidum Species Dipodascaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4890 Streptomyces rimosus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO8246 Lantana involucrata Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13305 Mammea africana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13607 Arenaria kansuensis Species Scolopacidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14190 Streptopelia orientalis Species Columbidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13305 Mammea africana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO14190 Streptopelia orientalis Species Columbidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13305 Mammea africana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8188 Hypoestes purpurea Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13607 Arenaria kansuensis Species Scolopacidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2510 Pteris argentea Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7350 Sitotroga cerealella Species Gelechiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13305 Mammea africana Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5412 Tedania anhelans Species Tedaniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4890 Streptomyces rimosus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6089 Metacalypogeia alternifolia Species Calypogeiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9032 Geotrichum candidum Species Dipodascaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11341 Eucalyptus piperita Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13497 Senecio trichopterygius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13607 Arenaria kansuensis Species Scolopacidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8246 Lantana involucrata Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13201 Diphasiastrum tristachyum Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14882 Collariella gracilis Species Chaetomiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14190 Streptopelia orientalis Species Columbidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8655 Wendlandia tinctoria Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7119 Endospermum diadenum Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8188 Hypoestes purpurea Species Acanthaceae 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
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens IC50 = 7700.0 nM PMID[15679319]
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens IC50 > 100000.0 nM PMID[15679319]

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 NPC158737 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
0.6667 Remote Similarity NPC476748
0.6596 Remote Similarity NPC600801
0.6226 Remote Similarity NPC143895
0.6154 Remote Similarity NPC192255
0.6154 Remote Similarity NPC110958
0.6154 Remote Similarity NPC19890
0.6 Remote Similarity NPC205915
0.5789 Remote Similarity NPC176586
0.5789 Remote Similarity NPC210354
0.5741 Remote Similarity NPC171550
0.5741 Remote Similarity NPC134764
0.569 Remote Similarity NPC191158
0.569 Remote Similarity NPC177644
0.5532 Remote Similarity NPC80241
0.5532 Remote Similarity NPC301641
0.5532 Remote Similarity NPC485483
0.5424 Remote Similarity NPC185908
0.5424 Remote Similarity NPC230968
0.5424 Remote Similarity NPC102260
0.5424 Remote Similarity NPC482891
0.5417 Remote Similarity NPC81067
0.5417 Remote Similarity NPC602945
0.54 Remote Similarity NPC344161
0.5333 Remote Similarity NPC473575
0.5323 Remote Similarity NPC145569
0.5273 Remote Similarity NPC474288
0.5254 Remote Similarity NPC18576
0.5238 Remote Similarity NPC487679
0.5238 Remote Similarity NPC56184
0.5238 Remote Similarity NPC487678
0.52 Remote Similarity NPC40352
0.52 Remote Similarity NPC213711
0.5185 Remote Similarity NPC11453
0.5167 Remote Similarity NPC47181
0.5156 Remote Similarity NPC282291
0.5156 Remote Similarity NPC166137
0.5152 Remote Similarity NPC156376

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC158737 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