Natural Product: NPC202981

Natural Product IDNPC202981
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S)-Sativanone
IUPAC Name (3S)-7-hydroxy-3-(4-methoxyphenyl)-2,3-dihydrochromen-4-one
Synonyms (3S)-Sativanone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1087010
PubChem CID 46881075
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids

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 INYISIYHXQDCPK-CQSZACIVSA-N
Standard InCHI InChI=1S/C16H14O4/c1-19-12-5-2-10(3-6-12)14-9-20-15-8-11(17)4-7-13(15)16(14)18/h2-8,14,17H,9H2,1H3/t14-/m1/s1
SMILES COc1ccc(cc1)[C@H]1COc2c(C1=O)ccc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   270.09 Volume:   276.329
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Van der Waals volume.
Dense:   0.977 LogP:   3.062
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.1
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.301
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   55.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.911 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.588 Fsp3:   0.188
MCE-18:   51.368
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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:   0.319 Fluc inhibitor:   0.99
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.199
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.355
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.498 Promiscuous compounds:   0.155

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.702 MDCK Permeability:   -4.67
Pgp-inhibitor:   0.048 Pgp-substrate:   0.351
PAMPA:   0.291
?
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%):   0.108 30% Bioavailability (F30%):   0.027
50% Bioavailability (F50%):   0.223

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.689
Plasma Protein Binding (PPB):   92.873% Volume Distribution (VD):   -0.079
Fu: 9.783%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.907
OATP1B3 inhibitor:   0.84 BCRP inhibitor:   0.565
BSEP inhibitor:   0.747

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.081
CYP2C19-inhibitor:   0.979 CYP2C19-substrate:   0.74
CYP2C9-inhibitor:   0.271 CYP2C9-substrate:   0.012
CYP2D6-inhibitor:   0.91 CYP2D6-substrate:   0.975
CYP3A4-inhibitor:   0.618 CYP3A4-substrate:   0.011
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.18
HLM stability:   0.213
?
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):  5.56 Half-life (T1/2):  1.024

ADMET: Toxicity

hERG Blockers:  0.202 hERG Blockers (10um):  0.559
Human Hepatotoxicity (H-HT):  0.678 Drug-induced Liver Injury (DILI):  0.395
AMES Toxicity:  0.709 Rat Oral Acute Toxicity:  0.573
Maximum Recommended Daily Dose:  0.469 Skin Sensitization:  0.641
Carcinogencity:  0.763 Eye Corrosion:  0.141
Eye Irritation:  0.98 Respiratory Toxicity:  0.66
Drug-induced Neurotoxicity:  0.593 Ototoxicity:  0.228
Hematotoxicity:  0.313 Drug-induced Nephrotoxicity:  0.429
Genotoxicity:  0.776 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.156 Hek293 Cytotoxicity:  0.585
BCF:   1.511
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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:   4.116
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.287
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.76
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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
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[19928832]
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14114 Dalbergia parviflora 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
NPT396 Cell line T47D Homo sapiens Activity = 1.1 uM PMID[19928832]
NPT396 Cell line T47D Homo sapiens Activity = 0.7 uM PMID[19928832]
NPT83 Cell line MCF7 Homo sapiens Activity > 100.0 uM PMID[19928832]
NPT396 Cell line T47D Homo sapiens Activity = 9.2 uM PMID[19928832]
NPT396 Cell line T47D Homo sapiens Activity = 2.0 uM PMID[19928832]
NPT83 Cell line MCF7 Homo sapiens Activity = 8.6 uM PMID[19928832]
NPT83 Cell line MCF7 Homo sapiens Activity = 2.7 uM PMID[19928832]

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 NPC202981 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 NPC488571
0.7917 Intermediate Similarity NPC469550
0.7551 Intermediate Similarity NPC303185
0.7551 Intermediate Similarity NPC184649
0.7551 Intermediate Similarity NPC133501
0.74 Intermediate Similarity NPC299011
0.72 Intermediate Similarity NPC255807
0.72 Intermediate Similarity NPC31018
0.7059 Intermediate Similarity NPC181960
0.6923 Remote Similarity NPC488568
0.6731 Remote Similarity NPC129684
0.6731 Remote Similarity NPC299520
0.5849 Remote Similarity NPC479545
0.566 Remote Similarity NPC316480
0.566 Remote Similarity NPC470511
0.5536 Remote Similarity NPC311144
0.5263 Remote Similarity NPC260979
0.5263 Remote Similarity NPC188947
0.5217 Remote Similarity NPC80694
0.5088 Remote Similarity NPC267117
0.5088 Remote Similarity NPC113770

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC202981 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
0.5172 Remote Similarity NPD4908 Phase 1

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