Natural Product: NPC299011

Natural Product IDNPC299011
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3R)-Sativanone
IUPAC Name (3R)-3-(2,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2397752
PubChem CID 5321142
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 JOVYBWHPTQRVNZ-AWEZNQCLSA-N
Standard InCHI InChI=1S/C17H16O5/c1-20-11-4-6-12(15(8-11)21-2)14-9-22-16-7-10(18)3-5-13(16)17(14)19/h3-8,14,18H,9H2,1-2H3/t14-/m0/s1
SMILES COc1cc(OC)ccc1[C@@H]1COc2c(C1=O)ccc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
?
Van der Waals volume.
Dense:   0.992 LogP:   2.565
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.777
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.213
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   64.99
?
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:   0.944 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.713 Fsp3:   0.235
MCE-18:   54.238
?
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:   0.157 Fluc inhibitor:   0.982
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.193
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.26
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.36 Promiscuous compounds:   0.347

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.698 MDCK Permeability:   -4.687
Pgp-inhibitor:   0.041 Pgp-substrate:   0.115
PAMPA:   0.018
?
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):   0.001
20% Bioavailability (F20%):   0.203 30% Bioavailability (F30%):   0.141
50% Bioavailability (F50%):   0.81

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.765
Plasma Protein Binding (PPB):   90.702% Volume Distribution (VD):   0.047
Fu: 10.416%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.938
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.85
BSEP inhibitor:   0.885

ADMET: Metabolism

CYP1A2-inhibitor:   0.983 CYP1A2-substrate:   0.856
CYP2C19-inhibitor:   0.993 CYP2C19-substrate:   0.63
CYP2C9-inhibitor:   0.977 CYP2C9-substrate:   0.09
CYP2D6-inhibitor:   0.98 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.76 CYP3A4-substrate:   0.157
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.002
HLM stability:   0.495
?
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):  5.319 Half-life (T1/2):  2.066

ADMET: Toxicity

hERG Blockers:  0.241 hERG Blockers (10um):  0.588
Human Hepatotoxicity (H-HT):  0.66 Drug-induced Liver Injury (DILI):  0.882
AMES Toxicity:  0.566 Rat Oral Acute Toxicity:  0.47
Maximum Recommended Daily Dose:  0.487 Skin Sensitization:  0.76
Carcinogencity:  0.824 Eye Corrosion:  0.084
Eye Irritation:  0.971 Respiratory Toxicity:  0.935
Drug-induced Neurotoxicity:  0.767 Ototoxicity:  0.371
Hematotoxicity:  0.441 Drug-induced Nephrotoxicity:  0.622
Genotoxicity:  0.719 RPMI-8226 Immunitoxicity:  0.096
A549 Cytotoxicity:  0.366 Hek293 Cytotoxicity:  0.629
BCF:   1.019
?
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:   3.723
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.825
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.255
?
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
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota stem bark Indonesia 1999-SEP PMID[14510596]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. stem n.a. PMID[14510596]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[23743282]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota dry stem n.a. n.a. PMID[25466192]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota Roots n.a. n.a. PMID[29482940]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9525107]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22420 Lignum dalbergiae odoriferae rosewood n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30165 Pongamia pinnata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22420 Lignum dalbergiae odoriferae rosewood n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18117 Dalbergia odorifera Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18117 Dalbergia odorifera 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
NPT34 Cell line BV-2 Mus musculus IC50 > 50000.0 nM PMID[29482940]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[23743282]

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 NPC299011 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
0.7647 Intermediate Similarity NPC181960
0.7451 Intermediate Similarity NPC255807
0.7451 Intermediate Similarity NPC31018
0.74 Intermediate Similarity NPC202981
0.74 Intermediate Similarity NPC488571
0.7308 Intermediate Similarity NPC129684
0.7308 Intermediate Similarity NPC299520
0.7115 Intermediate Similarity NPC303185
0.7115 Intermediate Similarity NPC184649
0.7115 Intermediate Similarity NPC133501
0.6667 Remote Similarity NPC311144
0.6481 Remote Similarity NPC469550
0.625 Remote Similarity NPC488568
0.5593 Remote Similarity NPC39064
0.5593 Remote Similarity NPC47283
0.5517 Remote Similarity NPC471229
0.5333 Remote Similarity NPC32633
0.5167 Remote Similarity NPC482076
0.5088 Remote Similarity NPC470511

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC299011 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