Natural Product: NPC543685

Natural Product IDNPC543685
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Methylporiol
IUPAC Name (2~{S})-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-6-methyl-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 LNRAFJFUMJDPEP-AWEZNQCLSA-N
Standard InCHI InChI=1S/C17H16O5/c1-9-13(21-2)8-15-16(17(9)20)12(19)7-14(22-15)10-3-5-11(18)6-4-10/h3-6,8,14,18,20H,7H2,1-2H3/t14-/m0/s1
SMILES COC1=CC2=C(C(=O)C[C@@H](C3=CC=C(O)C=C3)O2)C(O)=C1C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   302.415
?
Van der Waals volume.
Dense:   0.992 LogP:   3.18
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.028
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.69
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   75.99
?
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:   0.891 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.856 Fsp3:   0.235
MCE-18:   57.429
?
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:   0.527 Fluc inhibitor:   0.787
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.27
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.291
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.295 Promiscuous compounds:   0.075

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.994 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.996 Pgp-substrate:   0.111
PAMPA:   0.343
?
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%):   0.632
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.948
Plasma Protein Binding (PPB):   96.77% Volume Distribution (VD):   -0.14
Fu: 3.108%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.946 CYP1A2-substrate:   0.913
CYP2C19-inhibitor:   0.158 CYP2C19-substrate:   0.971
CYP2C9-inhibitor:   0.717 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.801 CYP2D6-substrate:   0.912
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.079
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.801
HLM stability:   0.886
?
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):  5.81 Half-life (T1/2):  1.224

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.495
Human Hepatotoxicity (H-HT):  0.737 Drug-induced Liver Injury (DILI):  0.261
AMES Toxicity:  0.653 Rat Oral Acute Toxicity:  0.503
Maximum Recommended Daily Dose:  0.567 Skin Sensitization:  0.801
Carcinogencity:  0.63 Eye Corrosion:  0.032
Eye Irritation:  0.991 Respiratory Toxicity:  0.231
Drug-induced Neurotoxicity:  0.817 Ototoxicity:  0.368
Hematotoxicity:  0.194 Drug-induced Nephrotoxicity:  0.612
Genotoxicity:  0.86 RPMI-8226 Immunitoxicity:  0.14
A549 Cytotoxicity:  0.326 Hek293 Cytotoxicity:  0.57
BCF:   1.174
?
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:   3.825
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.058
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.361
?
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
NPO50072 Callistemon Genus Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO57793 Callistemon acuminatus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC543685 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
0.7347 Intermediate Similarity NPC480993
0.7347 Intermediate Similarity NPC329203
0.7347 Intermediate Similarity NPC222342
0.72 Intermediate Similarity NPC485881
0.72 Intermediate Similarity NPC475267
0.7 Intermediate Similarity NPC324386
0.6909 Remote Similarity NPC69674
0.6786 Remote Similarity NPC470131
0.6786 Remote Similarity NPC470132
0.6735 Remote Similarity NPC225153
0.6735 Remote Similarity NPC479876
0.6667 Remote Similarity NPC486094
0.6538 Remote Similarity NPC606248
0.6471 Remote Similarity NPC167624
0.6471 Remote Similarity NPC166482
0.6275 Remote Similarity NPC32441
0.6275 Remote Similarity NPC79943
0.6275 Remote Similarity NPC603284
0.6226 Remote Similarity NPC210084
0.6038 Remote Similarity NPC300668
0.6 Remote Similarity NPC329225
0.6 Remote Similarity NPC147686
0.5962 Remote Similarity NPC6407
0.5962 Remote Similarity NPC545184
0.5926 Remote Similarity NPC469764
0.5849 Remote Similarity NPC150648
0.5741 Remote Similarity NPC110038
0.569 Remote Similarity NPC169591
0.569 Remote Similarity NPC298223
0.569 Remote Similarity NPC604412
0.5667 Remote Similarity NPC470135
0.5606 Remote Similarity NPC472636
0.5577 Remote Similarity NPC265871
0.5577 Remote Similarity NPC205093
0.5556 Remote Similarity NPC312391
0.5536 Remote Similarity NPC310135
0.5536 Remote Similarity NPC2416
0.5472 Remote Similarity NPC188243
0.5472 Remote Similarity NPC110228
0.5455 Remote Similarity NPC274784
0.5455 Remote Similarity NPC73028
0.5455 Remote Similarity NPC488553
0.5455 Remote Similarity NPC20709
0.5455 Remote Similarity NPC296917
0.5455 Remote Similarity NPC170907
0.541 Remote Similarity NPC470133
0.541 Remote Similarity NPC220998
0.541 Remote Similarity NPC477840
0.5263 Remote Similarity NPC18727
0.5263 Remote Similarity NPC48208
0.5263 Remote Similarity NPC271590
0.5263 Remote Similarity NPC601395
0.5254 Remote Similarity NPC236637
0.5185 Remote Similarity NPC476480
0.5185 Remote Similarity NPC84585
0.5185 Remote Similarity NPC477243
0.5179 Remote Similarity NPC255106
0.5179 Remote Similarity NPC194432
0.5179 Remote Similarity NPC482119
0.5179 Remote Similarity NPC235165
0.5179 Remote Similarity NPC482120
0.5179 Remote Similarity NPC215885
0.5179 Remote Similarity NPC110776
0.5091 Remote Similarity NPC100099
0.5091 Remote Similarity NPC248372
0.5091 Remote Similarity NPC243083
0.5091 Remote Similarity NPC13768
0.5091 Remote Similarity NPC287246
0.5088 Remote Similarity NPC321011
0.5088 Remote Similarity NPC294852
0.5088 Remote Similarity NPC192083
0.5088 Remote Similarity NPC480992
0.5088 Remote Similarity NPC188679
0.5085 Remote Similarity NPC474836
0.5082 Remote Similarity NPC39329
0.5082 Remote Similarity NPC472580
0.5082 Remote Similarity NPC51032
0.5079 Remote Similarity NPC134171
0.5079 Remote Similarity NPC76338
0.5079 Remote Similarity NPC250242
0.5075 Remote Similarity NPC228504

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC543685 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
0.6275 Remote Similarity NPD1552 Clinical (unspecified phase)
0.6 Remote Similarity NPD1549 Phase 2
0.5091 Remote Similarity NPD1550 Phase 2
0.5088 Remote Similarity NPD2393 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