Natural Product: NPC242100

Natural Product IDNPC242100
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Perforamone D
IUPAC Name 5-hydroxy-2-(hydroxymethyl)-8,8-dimethylpyrano[2,3-h]chromen-4-one
Synonyms Perforamone D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2204370
PubChem CID 441980
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 QLDUXSCWWAQMTC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O5/c1-15(2)4-3-9-12(20-15)6-11(18)13-10(17)5-8(7-16)19-14(9)13/h3-6,16,18H,7H2,1-2H3
SMILES OCc1cc(=O)c2c(o1)c1C=CC(Oc1cc2O)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.08 Volume:   270.459
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Van der Waals volume.
Dense:   1.013 LogP:   2.314
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.38
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.01
?
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:   3.081 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:   0.176 Fluc inhibitor:   0.205
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.775
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.497
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.179 Promiscuous compounds:   0.36

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.905 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.679 Pgp-substrate:   0.177
PAMPA:   0.445
?
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):   0.025
20% Bioavailability (F20%):   0.82 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.278 MRP1:   0.83
Plasma Protein Binding (PPB):   93.035% Volume Distribution (VD):   0.16
Fu: 6.983%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.882 BCRP inhibitor:   0.86
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.045 CYP1A2-substrate:   0.023
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.526 CYP2C9-substrate:   0.053
CYP2D6-inhibitor:   0.161 CYP2D6-substrate:   0.046
CYP3A4-inhibitor:   0.019 CYP3A4-substrate:   0.94
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.187
HLM stability:   0.293
?
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):  5.219 Half-life (T1/2):  1.257

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.339
Human Hepatotoxicity (H-HT):  0.522 Drug-induced Liver Injury (DILI):  0.899
AMES Toxicity:  0.754 Rat Oral Acute Toxicity:  0.38
Maximum Recommended Daily Dose:  0.519 Skin Sensitization:  0.496
Carcinogencity:  0.929 Eye Corrosion:  0.066
Eye Irritation:  0.946 Respiratory Toxicity:  0.799
Drug-induced Neurotoxicity:  0.135 Ototoxicity:  0.164
Hematotoxicity:  0.219 Drug-induced Nephrotoxicity:  0.158
Genotoxicity:  0.944 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.051 Hek293 Cytotoxicity:  0.313
BCF:   1.213
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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:   3.663
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.463
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.596
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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
NPO21362 Harrisonia perforata Species Rutaceae Eukaryota n.a. root n.a. PMID[16394547]
NPO21362 Harrisonia perforata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[23688954]
NPO21362 Harrisonia perforata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21362 Harrisonia perforata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21362 Harrisonia perforata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21362 Harrisonia perforata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21362 Harrisonia perforata Species Rutaceae 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 = 25.0 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 NPC242100 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
0.7258 Intermediate Similarity NPC211811
0.7188 Intermediate Similarity NPC57393
0.625 Remote Similarity NPC255133
0.5882 Remote Similarity NPC293852
0.5797 Remote Similarity NPC170492
0.5789 Remote Similarity NPC482604
0.5634 Remote Similarity NPC471984
0.5541 Remote Similarity NPC329678
0.5507 Remote Similarity NPC24673
0.5429 Remote Similarity NPC275122
0.5429 Remote Similarity NPC55662
0.5429 Remote Similarity NPC120105
0.5429 Remote Similarity NPC5322
0.5352 Remote Similarity NPC166757
0.5342 Remote Similarity NPC261470
0.5325 Remote Similarity NPC40037
0.5238 Remote Similarity NPC482603
0.5135 Remote Similarity NPC15435
0.5075 Remote Similarity NPC46869
0.5067 Remote Similarity NPC38219

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC242100 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