Natural Product: NPC515607

Natural Product IDNPC515607
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-dimethyl-chroman-4-one
IUPAC Name (2~{R})-5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-dimethyl-chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 DYHOLQACRGJEHX-CYBMUJFWSA-N
Standard InCHI InChI=1S/C17H16O5/c1-8-15(20)9(2)17-14(16(8)21)12(19)7-13(22-17)10-3-5-11(18)6-4-10/h3-6,13,18,20-21H,7H2,1-2H3/t13-/m1/s1
SMILES CC1=C(O)C(C)=C2O[C@@H](C3=CC=C(O)C=C3)CC(=O)C2=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
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Van der Waals volume.
Dense:   0.992 LogP:   2.952
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.736
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.526
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   86.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.753 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.027 Fsp3:   0.235
MCE-18:   60.619
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.666 Fluc inhibitor:   0.806
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.275
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.199
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.357 Promiscuous compounds:   0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.135 MDCK Permeability:   -4.786
Pgp-inhibitor:   0.238 Pgp-substrate:   0.033
PAMPA:   0.688
?
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%):   0.003 30% Bioavailability (F30%):   0.034
50% Bioavailability (F50%):   0.333

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.995
Plasma Protein Binding (PPB):   96.041% Volume Distribution (VD):   -0.056
Fu: 4.679%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.739
OATP1B3 inhibitor:   0.668 BCRP inhibitor:   0.228
BSEP inhibitor:   0.869

ADMET: Metabolism

CYP1A2-inhibitor:   0.652 CYP1A2-substrate:   0.67
CYP2C19-inhibitor:   0.016 CYP2C19-substrate:   0.894
CYP2C9-inhibitor:   0.039 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.104 CYP2D6-substrate:   0.155
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.861
HLM stability:   0.86
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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):  7.639 Half-life (T1/2):  1.137

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.477
Human Hepatotoxicity (H-HT):  0.784 Drug-induced Liver Injury (DILI):  0.34
AMES Toxicity:  0.626 Rat Oral Acute Toxicity:  0.741
Maximum Recommended Daily Dose:  0.711 Skin Sensitization:  0.951
Carcinogencity:  0.343 Eye Corrosion:  0.149
Eye Irritation:  0.996 Respiratory Toxicity:  0.949
Drug-induced Neurotoxicity:  0.658 Ototoxicity:  0.374
Hematotoxicity:  0.153 Drug-induced Nephrotoxicity:  0.375
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.709 Hek293 Cytotoxicity:  0.647
BCF:   1.207
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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:   3.984
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.013
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.484
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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
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. whole plant n.a. DOI[10.1007/BF02329610]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. PMID[15270561]
NPO12987 Rhododendron farrerae Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25440 Phormium tenax Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53494 Pancratium maritimum L. Genus Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO50182 Angophora lanceolata Genus Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2177 Rhododendron spp. Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44501 Cyrtomium spp. Genus Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25440 Phormium tenax Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2177 Rhododendron spp. Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25440 Phormium tenax Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25440 Phormium tenax Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21072 Rhododendron dauricum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12987 Rhododendron farrerae Species Ericaceae 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

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 NPC515607 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 NPC167624
1.0 High Similarity NPC166482
0.8043 Intermediate Similarity NPC248372
0.7917 Intermediate Similarity NPC192083
0.7708 Intermediate Similarity NPC296917
0.7708 Intermediate Similarity NPC170907
0.7551 Intermediate Similarity NPC485881
0.7292 Intermediate Similarity NPC603284
0.6863 Remote Similarity NPC324134
0.6863 Remote Similarity NPC480995
0.6863 Remote Similarity NPC40833
0.6863 Remote Similarity NPC477503
0.6667 Remote Similarity NPC270789
0.6667 Remote Similarity NPC324386
0.6346 Remote Similarity NPC110776
0.6182 Remote Similarity NPC231134
0.6038 Remote Similarity NPC110038
0.5818 Remote Similarity NPC2416
0.5769 Remote Similarity NPC213322
0.5763 Remote Similarity NPC265040
0.5686 Remote Similarity NPC329225
0.5686 Remote Similarity NPC147686
0.566 Remote Similarity NPC32441
0.566 Remote Similarity NPC79943
0.5536 Remote Similarity NPC271590
0.5472 Remote Similarity NPC225153
0.5472 Remote Similarity NPC479876
0.5455 Remote Similarity NPC300668
0.5455 Remote Similarity NPC215885
0.5455 Remote Similarity NPC329203
0.5455 Remote Similarity NPC222342
0.5424 Remote Similarity NPC480991
0.5357 Remote Similarity NPC469764
0.5357 Remote Similarity NPC480992
0.5357 Remote Similarity NPC475267
0.5357 Remote Similarity NPC606248
0.5333 Remote Similarity NPC107572
0.5333 Remote Similarity NPC32739
0.5312 Remote Similarity NPC473078
0.5286 Remote Similarity NPC483810
0.5273 Remote Similarity NPC312391
0.5167 Remote Similarity NPC164980
0.5161 Remote Similarity NPC470133
0.5161 Remote Similarity NPC220998
0.5152 Remote Similarity NPC246948
0.5152 Remote Similarity NPC142405
0.5088 Remote Similarity NPC476153

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC515607 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
0.7917 Intermediate Similarity NPD2393 Clinical (unspecified phase)
0.5686 Remote Similarity NPD1549 Phase 2
0.566 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