Natural Product: NPC501514

Natural Product IDNPC501514
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R})-7-hydroxy-2-[4-hydroxy-3,5-bis(3-methylbut-2-enyl)phenyl]chroman-4-one
IUPAC Name (2~{R})-7-hydroxy-2-[4-hydroxy-3,5-bis(3-methylbut-2-enyl)phenyl]chroman-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003643] 3'-prenylated flavans
            • [CHEMONTID:0003506] 3'-prenylated flavanones

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 JBQLRZGPTDOWQA-HSZRJFAPSA-N
Standard InCHI InChI=1S/C25H28O4/c1-15(2)5-7-17-11-19(12-18(25(17)28)8-6-16(3)4)23-14-22(27)21-10-9-20(26)13-24(21)29-23/h5-6,9-13,23,26,28H,7-8,14H2,1-4H3/t23-/m1/s1
SMILES CC(C)=CCC1=CC([C@H]2CC(=O)C3=CC=C(O)C=C3O2)=CC(CC=C(C)C)=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.2 Volume:   426.719
?
Van der Waals volume.
Dense:   0.919 LogP:   5.936
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.192
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.207
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   66.76
?
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:   0.629 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.417 Fsp3:   0.32
MCE-18:   62.424
?
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:   0.97 Fluc inhibitor:   0.954
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.237
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.319
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.492 Promiscuous compounds:   0.088

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.874 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.9 Pgp-substrate:   0.011
PAMPA:   0.723
?
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):   0.115
20% Bioavailability (F20%):   0.994 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.68
Plasma Protein Binding (PPB):   94.274% Volume Distribution (VD):   0.355
Fu: 5.913%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.962
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.891

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.099 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.807 CYP2D6-substrate:   0.195
CYP3A4-inhibitor:   0.034 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.113 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):  7.867 Half-life (T1/2):  1.493

ADMET: Toxicity

hERG Blockers:  0.133 hERG Blockers (10um):  0.625
Human Hepatotoxicity (H-HT):  0.747 Drug-induced Liver Injury (DILI):  0.423
AMES Toxicity:  0.793 Rat Oral Acute Toxicity:  0.78
Maximum Recommended Daily Dose:  0.744 Skin Sensitization:  0.956
Carcinogencity:  0.646 Eye Corrosion:  0.0
Eye Irritation:  0.713 Respiratory Toxicity:  0.732
Drug-induced Neurotoxicity:  0.84 Ototoxicity:  0.586
Hematotoxicity:  0.264 Drug-induced Nephrotoxicity:  0.804
Genotoxicity:  0.974 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.635 Hek293 Cytotoxicity:  0.734
BCF:   2.076
?
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:   5.236
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.802
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.27
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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
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota Stems; Barks n.a. n.a. PMID[12828487]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. bark n.a. PMID[14994185]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark n.a. n.a. PMID[17489632]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[17517504]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota Barks n.a. n.a. PMID[18302333]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. stem n.a. PMID[18484536]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota stem bark Mukono, Uganda 2005-JUN PMID[19008110]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19836230]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20337486]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20934335]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21116437]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23022281]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7964799]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8526 Erythrina abyssinica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24314 Erythrina sigmoidea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27387 Erythrina addisoniae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8526 Erythrina abyssinica 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 NPC501514 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 NPC143896
0.8519 High Similarity NPC221432
0.8519 High Similarity NPC257097
0.8036 Intermediate Similarity NPC68104
0.7797 Intermediate Similarity NPC291508
0.7069 Intermediate Similarity NPC39329
0.7069 Intermediate Similarity NPC51032
0.6897 Remote Similarity NPC258630
0.678 Remote Similarity NPC236766
0.6731 Remote Similarity NPC329225
0.6731 Remote Similarity NPC147686
0.6716 Remote Similarity NPC209040
0.6716 Remote Similarity NPC110303
0.6716 Remote Similarity NPC601247
0.6545 Remote Similarity NPC1612
0.6545 Remote Similarity NPC183959
0.6481 Remote Similarity NPC476480
0.6481 Remote Similarity NPC84585
0.6393 Remote Similarity NPC75049
0.6364 Remote Similarity NPC264083
0.6333 Remote Similarity NPC169591
0.6333 Remote Similarity NPC298223
0.6333 Remote Similarity NPC604412
0.629 Remote Similarity NPC109223
0.629 Remote Similarity NPC10937
0.6154 Remote Similarity NPC470890
0.6094 Remote Similarity NPC474033
0.6032 Remote Similarity NPC197252
0.5968 Remote Similarity NPC150408
0.5938 Remote Similarity NPC125855
0.5806 Remote Similarity NPC164980
0.5789 Remote Similarity NPC472460
0.5758 Remote Similarity NPC23728
0.5692 Remote Similarity NPC106976
0.5645 Remote Similarity NPC197351
0.5625 Remote Similarity NPC473413
0.5625 Remote Similarity NPC69674
0.5588 Remote Similarity NPC474034
0.5538 Remote Similarity NPC17170
0.5538 Remote Similarity NPC310130
0.5441 Remote Similarity NPC200761
0.5303 Remote Similarity NPC220998
0.5286 Remote Similarity NPC39752
0.5278 Remote Similarity NPC477958
0.5231 Remote Similarity NPC1089
0.5231 Remote Similarity NPC91560
0.5224 Remote Similarity NPC223500
0.5224 Remote Similarity NPC76338
0.5224 Remote Similarity NPC250242
0.5205 Remote Similarity NPC185276
0.5152 Remote Similarity NPC149026
0.5152 Remote Similarity NPC265040
0.5152 Remote Similarity NPC265075
0.5147 Remote Similarity NPC85121
0.5147 Remote Similarity NPC608140
0.5139 Remote Similarity NPC477957
0.5077 Remote Similarity NPC482704
0.5075 Remote Similarity NPC66515

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC501514 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
0.6731 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