Natural Product: NPC303967

Natural Product IDNPC303967
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (R)-4' '-Methoxydalbergione
IUPAC Name 2-methoxy-5-[(1R)-1-phenylprop-2-enyl]cyclohexa-2,5-diene-1,4-dione
Synonyms (R)-4' '-Methoxydalbergione
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL466581
PubChem CID 442809
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0001614] Neoflavonoids
        • [CHEMONTID:0001758] Dalbergiones

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 RGSUZUQISVAJJF-GFCCVEGCSA-N
Standard InCHI InChI=1S/C16H14O3/c1-3-12(11-7-5-4-6-8-11)13-9-15(18)16(19-2)10-14(13)17/h3-10,12H,1H2,2H3/t12-/m1/s1
SMILES COC1=CC(=O)C(=CC1=O)[C@@H](c1ccccc1)C=C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   254.09 Volume:   273.458
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Van der Waals volume.
Dense:   0.929 LogP:   2.843
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.971
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.561
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   15.0
TPSA:   43.37
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.612 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.182 Fsp3:   0.125
MCE-18:   36.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.592 Fluc inhibitor:   0.842
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.603
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.339
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.9 Promiscuous compounds:   0.216

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.51 MDCK Permeability:   -4.499
Pgp-inhibitor:   0.844 Pgp-substrate:   0.0
PAMPA:   0.328
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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):   0.055
20% Bioavailability (F20%):   0.366 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.279
Plasma Protein Binding (PPB):   95.911% Volume Distribution (VD):   0.176
Fu: 4.849%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.045
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.128 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.792 CYP2C19-substrate:   0.672
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.697
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.986
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.998
HLM stability:   0.727
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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):  3.492 Half-life (T1/2):  2.171

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.469
Human Hepatotoxicity (H-HT):  0.799 Drug-induced Liver Injury (DILI):  0.496
AMES Toxicity:  0.685 Rat Oral Acute Toxicity:  0.618
Maximum Recommended Daily Dose:  0.938 Skin Sensitization:  0.96
Carcinogencity:  0.428 Eye Corrosion:  0.068
Eye Irritation:  0.99 Respiratory Toxicity:  0.736
Drug-induced Neurotoxicity:  0.696 Ototoxicity:  0.107
Hematotoxicity:  0.58 Drug-induced Nephrotoxicity:  0.325
Genotoxicity:  0.985 RPMI-8226 Immunitoxicity:  0.158
A549 Cytotoxicity:  0.055 Hek293 Cytotoxicity:  0.599
BCF:   1.519
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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:   4.209
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.705
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.161
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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
NPO24287 Dalbergia louvelii Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[14640516]
NPO14270 Dalbergia louveli Species Fabaceae Eukaryota n.a. heartwood n.a. PMID[14640516]
NPO26331 Plumbago auriculata Species Plumbaginaceae Eukaryota n.a. flower n.a. PMID[22260638]
NPO20876 Arnica longifolia Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23743282]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9525107]
NPO14270 Dalbergia louveli Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23269 Spodoptera exigua Species Noctuidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26331 Plumbago auriculata Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20876 Arnica longifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17889 Clerodendrum indicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24287 Dalbergia louvelii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22848 Kaempferia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22848 Kaempferia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23821 Rubus rigidus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22848 Kaempferia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23821 Rubus rigidus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22848 Kaempferia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22848 Kaempferia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20876 Arnica longifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22848 Kaempferia galanga Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17889 Clerodendrum indicum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23269 Spodoptera exigua Species Noctuidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14270 Dalbergia louveli Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23821 Rubus rigidus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24287 Dalbergia louvelii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20888 Paraderris canarensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26331 Plumbago auriculata Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6173 Senegalia caesia 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
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 5800.0 nM PMID[14640516]

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 NPC303967 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 NPC67585
1.0 High Similarity NPC110420
0.7674 Intermediate Similarity NPC325646
0.7674 Intermediate Similarity NPC28951
0.6591 Remote Similarity NPC145052
0.6531 Remote Similarity NPC239302

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC303967 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