Natural Product: NPC316816

Natural Product IDNPC316816
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tephrocandidin A
IUPAC Name (2S)-7-hydroxy-8-[(Z)-3-hydroxy-3-methylbut-1-enyl]-5-methoxy-2-phenyl-2,3-dihydrochromen-4-one
Synonyms Tephrocandidin A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1784258
PubChem CID 54584962
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002590] 5-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 YSYPNKZOQYHUSV-IBSYWUHOSA-N
Standard InCHI InChI=1S/C21H22O5/c1-21(2,24)10-9-14-15(22)11-18(25-3)19-16(23)12-17(26-20(14)19)13-7-5-4-6-8-13/h4-11,17,22,24H,12H2,1-3H3/b10-9-/t17-/m0/s1
SMILES COc1cc(O)c(c2c1C(=O)C[C@H](O2)c1ccccc1)/C=CC(O)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   368.962
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Van der Waals volume.
Dense:   0.96 LogP:   3.613
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.374
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.836
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   75.99
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.871 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.299 Fsp3:   0.286
MCE-18:   62.963
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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:   0.497 Fluc inhibitor:   0.733
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.317
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.457
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.149 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.926 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.972 Pgp-substrate:   0.006
PAMPA:   0.184
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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):   0.001
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.361
50% Bioavailability (F50%):   0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.032 MRP1:   0.751
Plasma Protein Binding (PPB):   97.881% Volume Distribution (VD):   -0.2
Fu: 1.712%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.992
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.907 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.193 CYP2C19-substrate:   0.941
CYP2C9-inhibitor:   0.145 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.709
CYP3A4-inhibitor:   0.087 CYP3A4-substrate:   0.024
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.54
HLM stability:   0.786
?
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):  4.896 Half-life (T1/2):  1.255

ADMET: Toxicity

hERG Blockers:  0.137 hERG Blockers (10um):  0.398
Human Hepatotoxicity (H-HT):  0.882 Drug-induced Liver Injury (DILI):  0.241
AMES Toxicity:  0.732 Rat Oral Acute Toxicity:  0.466
Maximum Recommended Daily Dose:  0.669 Skin Sensitization:  0.877
Carcinogencity:  0.53 Eye Corrosion:  0.004
Eye Irritation:  0.967 Respiratory Toxicity:  0.13
Drug-induced Neurotoxicity:  0.855 Ototoxicity:  0.481
Hematotoxicity:  0.293 Drug-induced Nephrotoxicity:  0.871
Genotoxicity:  0.916 RPMI-8226 Immunitoxicity:  0.172
A549 Cytotoxicity:  0.295 Hek293 Cytotoxicity:  0.405
BCF:   1.156
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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:   3.787
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.371
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.686
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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
NPO20204 Tephrosia candida Species Fabaceae Eukaryota n.a. aerial part n.a. PMID[21510635]
NPO20204 Tephrosia candida Species Fabaceae Eukaryota aerial parts Limbe (South West) Province, Cameroon 2007-APR PMID[21510635]
NPO20204 Tephrosia candida Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20204 Tephrosia candida 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
NPT108 Individual protein Estrogen receptor alpha Homo sapiens Inhibition = 70.1 % PMID[21510635]
NPT108 Individual protein Estrogen receptor alpha Homo sapiens IC50 = 3500000.0 nM PMID[21510635]

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 NPC316816 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
0.6964 Remote Similarity NPC177354
0.629 Remote Similarity NPC147145
0.6 Remote Similarity NPC175504
0.5862 Remote Similarity NPC265871
0.5862 Remote Similarity NPC205093
0.5738 Remote Similarity NPC194432
0.5606 Remote Similarity NPC109183
0.5588 Remote Similarity NPC76338
0.5588 Remote Similarity NPC250242
0.5441 Remote Similarity NPC176229
0.5397 Remote Similarity NPC476153
0.5373 Remote Similarity NPC608647
0.527 Remote Similarity NPC485619
0.5246 Remote Similarity NPC22467
0.5246 Remote Similarity NPC225153
0.5246 Remote Similarity NPC479876
0.5217 Remote Similarity NPC470133
0.5152 Remote Similarity NPC259685
0.5147 Remote Similarity NPC87486
0.5147 Remote Similarity NPC124780
0.5079 Remote Similarity NPC150648
0.5079 Remote Similarity NPC37392

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC316816 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