Natural Product: NPC495806

Natural Product IDNPC495806
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-hydroxy-2-(4-hydroxyphenyl)-6-(3-methylbut-2-enyl)chroman-4-one
IUPAC Name (2~{R})-5-hydroxy-2-(4-hydroxyphenyl)-6-(3-methylbut-2-enyl)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 DTZBWBKUXVNGMX-GOSISDBHSA-N
Standard InCHI InChI=1S/C20H20O4/c1-12(2)3-4-14-7-10-17-19(20(14)23)16(22)11-18(24-17)13-5-8-15(21)9-6-13/h3,5-10,18,21,23H,4,11H2,1-2H3/t18-/m1/s1
SMILES CC(C)=CCC1=CC=C2O[C@@H](C3=CC=C(O)C=C3)CC(=O)C2=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   324.14 Volume:   342.876
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Van der Waals volume.
Dense:   0.945 LogP:   4.479
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.728
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.75
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   66.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.826 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.04 Fsp3:   0.25
MCE-18:   56.88
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.849 Fluc inhibitor:   0.96
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.392
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.304
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.456 Promiscuous compounds:   0.075

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.868 MDCK Permeability:   -4.71
Pgp-inhibitor:   0.408 Pgp-substrate:   0.253
PAMPA:   0.676
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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):   0.0
20% Bioavailability (F20%):   0.082 30% Bioavailability (F30%):   0.854
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.955
Plasma Protein Binding (PPB):   96.451% Volume Distribution (VD):   -0.021
Fu: 2.923%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.137
OATP1B3 inhibitor:   0.738 BCRP inhibitor:   0.98
BSEP inhibitor:   0.572

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.173 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.058 CYP2D6-substrate:   0.123
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  8.829 Half-life (T1/2):  1.31

ADMET: Toxicity

hERG Blockers:  0.159 hERG Blockers (10um):  0.559
Human Hepatotoxicity (H-HT):  0.803 Drug-induced Liver Injury (DILI):  0.577
AMES Toxicity:  0.705 Rat Oral Acute Toxicity:  0.748
Maximum Recommended Daily Dose:  0.711 Skin Sensitization:  0.974
Carcinogencity:  0.326 Eye Corrosion:  0.009
Eye Irritation:  0.952 Respiratory Toxicity:  0.916
Drug-induced Neurotoxicity:  0.86 Ototoxicity:  0.52
Hematotoxicity:  0.172 Drug-induced Nephrotoxicity:  0.849
Genotoxicity:  0.97 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.79 Hek293 Cytotoxicity:  0.674
BCF:   1.699
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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:   4.738
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.023
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.575
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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
NPO23416 Crotalaria ramosissima Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO54132 Crotolaria ramosissima n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23416 Crotalaria ramosissima 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

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 NPC495806 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
0.7368 Intermediate Similarity NPC69674
0.6897 Remote Similarity NPC39329
0.6897 Remote Similarity NPC51032
0.6724 Remote Similarity NPC169591
0.6724 Remote Similarity NPC298223
0.6724 Remote Similarity NPC604412
0.6557 Remote Similarity NPC125855
0.65 Remote Similarity NPC265040
0.65 Remote Similarity NPC75049
0.6441 Remote Similarity NPC143896
0.6393 Remote Similarity NPC109223
0.6393 Remote Similarity NPC220998
0.6393 Remote Similarity NPC10937
0.6333 Remote Similarity NPC1089
0.6333 Remote Similarity NPC107572
0.6333 Remote Similarity NPC32739
0.623 Remote Similarity NPC221432
0.623 Remote Similarity NPC257097
0.6212 Remote Similarity NPC228504
0.6167 Remote Similarity NPC258630
0.6 Remote Similarity NPC473078
0.5965 Remote Similarity NPC324386
0.5902 Remote Similarity NPC164980
0.5862 Remote Similarity NPC469764
0.5821 Remote Similarity NPC246948
0.5821 Remote Similarity NPC142405
0.5797 Remote Similarity NPC488556
0.5781 Remote Similarity NPC223500
0.5781 Remote Similarity NPC486094
0.5781 Remote Similarity NPC76338
0.5781 Remote Similarity NPC250242
0.5714 Remote Similarity NPC472627
0.5714 Remote Similarity NPC185276
0.5692 Remote Similarity NPC608140
0.569 Remote Similarity NPC300668
0.5672 Remote Similarity NPC35038
0.5652 Remote Similarity NPC472629
0.5625 Remote Similarity NPC68104
0.5625 Remote Similarity NPC66515
0.5614 Remote Similarity NPC32441
0.5614 Remote Similarity NPC79943
0.5571 Remote Similarity NPC472636
0.5556 Remote Similarity NPC472628
0.5538 Remote Similarity NPC106976
0.5522 Remote Similarity NPC470890
0.5522 Remote Similarity NPC291508
0.5469 Remote Similarity NPC95936
0.5424 Remote Similarity NPC329203
0.5424 Remote Similarity NPC222342
0.5397 Remote Similarity NPC76372
0.5397 Remote Similarity NPC37496
0.5385 Remote Similarity NPC17170
0.5385 Remote Similarity NPC197252
0.5385 Remote Similarity NPC610133
0.5373 Remote Similarity NPC161506
0.5362 Remote Similarity NPC166934
0.5357 Remote Similarity NPC329225
0.5357 Remote Similarity NPC147686
0.5342 Remote Similarity NPC312273
0.5333 Remote Similarity NPC475267
0.5333 Remote Similarity NPC606248
0.5312 Remote Similarity NPC236766
0.5312 Remote Similarity NPC150408
0.5303 Remote Similarity NPC166689
0.5294 Remote Similarity NPC200761
0.5254 Remote Similarity NPC167624
0.5254 Remote Similarity NPC166482
0.5231 Remote Similarity NPC250214
0.5211 Remote Similarity NPC213896
0.5172 Remote Similarity NPC225153
0.5172 Remote Similarity NPC479876
0.5167 Remote Similarity NPC482119
0.5167 Remote Similarity NPC482120
0.5152 Remote Similarity NPC470131
0.5152 Remote Similarity NPC310130
0.5152 Remote Similarity NPC470135
0.5152 Remote Similarity NPC470132
0.5143 Remote Similarity NPC39752
0.5085 Remote Similarity NPC603284
0.5082 Remote Similarity NPC485881
0.5077 Remote Similarity NPC324436
0.5077 Remote Similarity NPC78
0.5077 Remote Similarity NPC472580
0.5075 Remote Similarity NPC285555

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC495806 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
0.5614 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5357 Remote Similarity NPD1549 Phase 2

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