Natural Product: NPC255133

Natural Product IDNPC255133
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Greveichromenol
IUPAC Name 5-hydroxy-8-(hydroxymethyl)-2,2-dimethylpyrano[3,2-g]chromen-6-one
Synonyms Greveichromenol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2204368
PubChem CID 71450427
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0003543] Pyranochromenes

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 MJSXHUBIQAPDNC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O5/c1-15(2)4-3-9-11(20-15)6-12-13(14(9)18)10(17)5-8(7-16)19-12/h3-6,16,18H,7H2,1-2H3
SMILES CC1(C)C=Cc2c(cc3c(c(=O)cc(CO)o3)c2O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.08 Volume:   270.459
?
Van der Waals volume.
Dense:   1.013 LogP:   2.232
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.377
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.897
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   79.9
?
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:   0.833 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.055 Fsp3:   0.267
MCE-18:   40.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.141 Fluc inhibitor:   0.343
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.382
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.443
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.186 Promiscuous compounds:   0.476

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.949 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.898 Pgp-substrate:   0.013
PAMPA:   0.453
?
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):   0.01
20% Bioavailability (F20%):   0.749 30% Bioavailability (F30%):   0.992
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.276 MRP1:   0.912
Plasma Protein Binding (PPB):   93.862% Volume Distribution (VD):   0.07
Fu: 5.896%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.798
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.046 CYP1A2-substrate:   0.203
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.981 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.266 CYP2D6-substrate:   0.022
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.901
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.933
HLM stability:   0.24
?
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):  4.963 Half-life (T1/2):  1.066

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.343
Human Hepatotoxicity (H-HT):  0.493 Drug-induced Liver Injury (DILI):  0.687
AMES Toxicity:  0.725 Rat Oral Acute Toxicity:  0.451
Maximum Recommended Daily Dose:  0.549 Skin Sensitization:  0.57
Carcinogencity:  0.891 Eye Corrosion:  0.08
Eye Irritation:  0.957 Respiratory Toxicity:  0.793
Drug-induced Neurotoxicity:  0.15 Ototoxicity:  0.2
Hematotoxicity:  0.222 Drug-induced Nephrotoxicity:  0.196
Genotoxicity:  0.895 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.065 Hek293 Cytotoxicity:  0.303
BCF:   0.934
?
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:   3.467
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.258
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.443
?
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
NPO19141 Aframomum melegueta Species Zingiberaceae Eukaryota Seeds n.a. n.a. PMID[22789014]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota fruits n.a. n.a. PMID[23265871]
NPO8415 Tetragonotheca ludoviciana Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO3848 Myrtopsis macrocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1513 Penicillium nalgiovense Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3268 Callyspongia flammea Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8415 Tetragonotheca ludoviciana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19141 Aframomum melegueta Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19141 Aframomum melegueta Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1953 Miltochrista calamina Species Erebidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6728 Rubus niveus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3435 Saussurea katochaete Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3268 Callyspongia flammea Species Callyspongiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO470 Prismatomeris connata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3089 Cistus villosus Species Cistaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8415 Tetragonotheca ludoviciana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7385 Schisandra sphenanthera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4194 Teucrium buxifolium Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4821 Hypselodoris infucata Species Chromodorididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1513 Penicillium nalgiovense Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3848 Myrtopsis macrocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7941 Marshallia obovata Species Asteraceae 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
NPT115 Organism Mycobacterium tuberculosis H37Ra Mycobacterium tuberculosis H37Ra MIC = 50.0 ug.mL-1 PMID[22280816]

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 NPC255133 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
0.6557 Remote Similarity NPC473076
0.625 Remote Similarity NPC242100
0.6207 Remote Similarity NPC471697
0.597 Remote Similarity NPC265932
0.5714 Remote Similarity NPC81474
0.5714 Remote Similarity NPC59739
0.5692 Remote Similarity NPC297788
0.5606 Remote Similarity NPC202494
0.5571 Remote Similarity NPC479165
0.5507 Remote Similarity NPC101957
0.5507 Remote Similarity NPC166054
0.5507 Remote Similarity NPC97716
0.5507 Remote Similarity NPC479166
0.5493 Remote Similarity NPC70272
0.5429 Remote Similarity NPC6633
0.5429 Remote Similarity NPC200246
0.5429 Remote Similarity NPC65491
0.5342 Remote Similarity NPC184547
0.5278 Remote Similarity NPC16492
0.5263 Remote Similarity NPC256141
0.52 Remote Similarity NPC184755
0.52 Remote Similarity NPC275780
0.5143 Remote Similarity NPC488812
0.5135 Remote Similarity NPC84124
0.5132 Remote Similarity NPC83922
0.5122 Remote Similarity NPC470354
0.5122 Remote Similarity NPC470352
0.5067 Remote Similarity NPC229632
0.5067 Remote Similarity NPC178964

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC255133 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