Natural Product: NPC73028

Natural Product IDNPC73028
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Blumeatin
IUPAC Name (2S)-2-(3,5-dihydroxyphenyl)-5-hydroxy-7-methoxy-2,3-dihydrochromen-4-one
Synonyms Blumeatin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2037158
PubChem CID 70696494
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 YEYLMQKEGSQNGZ-AWEZNQCLSA-N
Standard InCHI InChI=1S/C16H14O6/c1-21-11-5-12(19)16-13(20)7-14(22-15(16)6-11)8-2-9(17)4-10(18)3-8/h2-6,14,17-19H,7H2,1H3/t14-/m0/s1
SMILES COc1cc2O[C@@H](CC(=O)c2c(c1)O)c1cc(O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   293.909
?
Van der Waals volume.
Dense:   1.028 LogP:   2.96
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.987
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.151
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.789 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.008 Fsp3:   0.188
MCE-18:   57.789
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.559 Fluc inhibitor:   0.839
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.273
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.382
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.339 Promiscuous compounds:   0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.998 MDCK Permeability:   -4.798
Pgp-inhibitor:   0.164 Pgp-substrate:   0.006
PAMPA:   0.123
?
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%):   0.072 30% Bioavailability (F30%):   0.49
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.689
Plasma Protein Binding (PPB):   88.703% Volume Distribution (VD):   -0.004
Fu: 11.18%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.937
BSEP inhibitor:   0.277

ADMET: Metabolism

CYP1A2-inhibitor:   0.9 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   0.035 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.912
CYP3A4-inhibitor:   0.02 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.088
HLM stability:   0.859
?
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):  7.2 Half-life (T1/2):  1.454

ADMET: Toxicity

hERG Blockers:  0.141 hERG Blockers (10um):  0.476
Human Hepatotoxicity (H-HT):  0.74 Drug-induced Liver Injury (DILI):  0.773
AMES Toxicity:  0.763 Rat Oral Acute Toxicity:  0.673
Maximum Recommended Daily Dose:  0.888 Skin Sensitization:  0.811
Carcinogencity:  0.726 Eye Corrosion:  0.078
Eye Irritation:  0.995 Respiratory Toxicity:  0.918
Drug-induced Neurotoxicity:  0.587 Ototoxicity:  0.278
Hematotoxicity:  0.143 Drug-induced Nephrotoxicity:  0.506
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.137
A549 Cytotoxicity:  0.684 Hek293 Cytotoxicity:  0.791
BCF:   1.255
?
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:   3.65
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.197
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.184
?
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
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[ 21030913]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. flower n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. stem n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. leaf n.a. DOI[10.1007/s11418-006-0112-9]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[15787457]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[19719093]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. leaf n.a. PMID[21319848]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[22512738]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[32544201]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[6387056]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12477 Dodonaea viscosa Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21559 Blumea balsamifera Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12477 Dodonaea viscosa Species Sapindaceae 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
NPT520 Cell line 3T3-L1 Mus musculus Activity = 121.2 % PMID[22512738]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 161.3 % PMID[22512738]
NPT520 Cell line 3T3-L1 Mus musculus Activity = 219.2 % PMID[22512738]

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 NPC73028 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
0.7551 Intermediate Similarity NPC329203
0.7551 Intermediate Similarity NPC222342
0.75 Intermediate Similarity NPC6407
0.75 Intermediate Similarity NPC545184
0.7347 Intermediate Similarity NPC150648
0.7292 Intermediate Similarity NPC182421
0.7255 Intermediate Similarity NPC18727
0.7083 Intermediate Similarity NPC140890
0.6923 Remote Similarity NPC310135
0.6226 Remote Similarity NPC274784
0.6226 Remote Similarity NPC20709
0.6102 Remote Similarity NPC477840
0.5926 Remote Similarity NPC338131
0.5893 Remote Similarity NPC302950
0.5849 Remote Similarity NPC264083
0.5636 Remote Similarity NPC480993
0.5556 Remote Similarity NPC32441
0.5556 Remote Similarity NPC243083
0.5556 Remote Similarity NPC13768
0.5556 Remote Similarity NPC287246
0.5556 Remote Similarity NPC79943
0.5536 Remote Similarity NPC321011
0.5536 Remote Similarity NPC294852
0.5536 Remote Similarity NPC188679
0.5484 Remote Similarity NPC480158
0.5439 Remote Similarity NPC469758
0.5424 Remote Similarity NPC236637
0.5294 Remote Similarity NPC219163
0.5263 Remote Similarity NPC475267
0.5179 Remote Similarity NPC484336
0.5179 Remote Similarity NPC484337
0.5172 Remote Similarity NPC48208
0.5091 Remote Similarity NPC188243
0.5091 Remote Similarity NPC110228
0.5079 Remote Similarity NPC17170
0.5072 Remote Similarity NPC39351

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC73028 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
0.5893 Remote Similarity NPD1934 Phase 0
0.5556 Remote Similarity NPD1550 Phase 2
0.5556 Remote Similarity NPD1552 Clinical (unspecified phase)

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