Natural Product: NPC29734

Natural Product IDNPC29734
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-[(E,6R)-6-Hydroxy-7-Methoxy-3,7-Dimethyloct-2-Enoxy]Chromen-2-One
IUPAC Name 7-[(E,6R)-6-hydroxy-7-methoxy-3,7-dimethyloct-2-enoxy]chromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2346910
PubChem CID 15008366
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 HODOWBFKRLQCBH-GPZRYRNASA-N
Standard InCHI InChI=1S/C20H26O5/c1-14(5-9-18(21)20(2,3)23-4)11-12-24-16-8-6-15-7-10-19(22)25-17(15)13-16/h6-8,10-11,13,18,21H,5,9,12H2,1-4H3/b14-11+/t18-/m1/s1
SMILES C/C(=CCOc1ccc2ccc(=O)oc2c1)/CC[C@H](C(C)(C)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.18 Volume:   365.496
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Van der Waals volume.
Dense:   0.947 LogP:   3.459
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.239
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.304
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   13.0
TPSA:   68.9
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.583 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.268 Fsp3:   0.45
MCE-18:   30.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.409 Fluc inhibitor:   0.597
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.988
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.211
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.164 Promiscuous compounds:   0.018

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.865 MDCK Permeability:   -4.633
Pgp-inhibitor:   0.012 Pgp-substrate:   0.003
PAMPA:   0.71
?
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%):   0.887 30% Bioavailability (F30%):   0.534
50% Bioavailability (F50%):   0.486

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.998
Plasma Protein Binding (PPB):   93.064% Volume Distribution (VD):   0.079
Fu: 6.319%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.948

ADMET: Metabolism

CYP1A2-inhibitor:   0.308 CYP1A2-substrate:   0.059
CYP2C19-inhibitor:   0.659 CYP2C19-substrate:   0.66
CYP2C9-inhibitor:   0.59 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.314
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.97
CYP2B6-substrate:   0.0 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):  8.175 Half-life (T1/2):  0.609

ADMET: Toxicity

hERG Blockers:  0.393 hERG Blockers (10um):  0.554
Human Hepatotoxicity (H-HT):  0.592 Drug-induced Liver Injury (DILI):  0.755
AMES Toxicity:  0.503 Rat Oral Acute Toxicity:  0.416
Maximum Recommended Daily Dose:  0.742 Skin Sensitization:  0.355
Carcinogencity:  0.668 Eye Corrosion:  0.0
Eye Irritation:  0.416 Respiratory Toxicity:  0.886
Drug-induced Neurotoxicity:  0.38 Ototoxicity:  0.356
Hematotoxicity:  0.334 Drug-induced Nephrotoxicity:  0.378
Genotoxicity:  0.903 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.167 Hek293 Cytotoxicity:  0.542
BCF:   1.135
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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:   3.798
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.176
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.684
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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
NPO5045 Aegle marmelos Species Rutaceae Eukaryota leaves n.a. n.a. PMID[18760601]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. bark n.a. PMID[21875114]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[23434131]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. fruit n.a. PMID[26247834]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[30579794]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[31302251]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5045 Aegle marmelos Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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
NPT22409 Protein complex Mitochondrial complex I (NADH dehydrogenase) Homo sapiens IC50 > 30000.0 nM PMID[23434131]
NPT22409 Protein complex Mitochondrial complex I (NADH dehydrogenase) Homo sapiens IC50 = 19300.0 nM PMID[23434131]
NPT2 Others Unspecified n.a. Inhibition = 30.0 % PMID[18321710]

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 NPC29734 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
0.8033 Intermediate Similarity NPC479428
0.8033 Intermediate Similarity NPC121740
0.8033 Intermediate Similarity NPC113098
0.7778 Intermediate Similarity NPC2363
0.7313 Intermediate Similarity NPC267336
0.7313 Intermediate Similarity NPC272650
0.7258 Intermediate Similarity NPC180006
0.7231 Intermediate Similarity NPC601571
0.7188 Intermediate Similarity NPC224774
0.7031 Intermediate Similarity NPC235190
0.697 Remote Similarity NPC479429
0.697 Remote Similarity NPC479314
0.6923 Remote Similarity NPC33279
0.6897 Remote Similarity NPC281356
0.6875 Remote Similarity NPC479427
0.6761 Remote Similarity NPC131198
0.6714 Remote Similarity NPC258567
0.6618 Remote Similarity NPC479315
0.6486 Remote Similarity NPC471068
0.6486 Remote Similarity NPC471069
0.6486 Remote Similarity NPC471070
0.6438 Remote Similarity NPC14697
0.6301 Remote Similarity NPC481285
0.6234 Remote Similarity NPC469449
0.6104 Remote Similarity NPC469453
0.6081 Remote Similarity NPC14822
0.6076 Remote Similarity NPC471072
0.5854 Remote Similarity NPC471071
0.5479 Remote Similarity NPC164148
0.5479 Remote Similarity NPC43500
0.5385 Remote Similarity NPC138149
0.5385 Remote Similarity NPC20631
0.5385 Remote Similarity NPC93640
0.5385 Remote Similarity NPC603929
0.5352 Remote Similarity NPC241341
0.5345 Remote Similarity NPC265547
0.5316 Remote Similarity NPC318867
0.5316 Remote Similarity NPC146014
0.519 Remote Similarity NPC481286
0.5082 Remote Similarity NPC152306
0.5068 Remote Similarity NPC290764
0.5067 Remote Similarity NPC609959
0.5065 Remote Similarity NPC481284

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC29734 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