Natural Product: NPC281241

Natural Product IDNPC281241
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(9R)-8,8-Dimethyl-2-Oxo-9,10-Dihydropyrano[2,3-H]Chromen-9-Yl] 2-Methylpropanoate
IUPAC Name [(9R)-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-h]chromen-9-yl] 2-methylpropanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL449490
PubChem CID 11823236
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0003484] Pyranocoumarins
          • [CHEMONTID:0003485] Angular pyranocoumarins

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 PKHNHXIOSSYBJU-CQSZACIVSA-N
Standard InCHI InChI=1S/C18H20O5/c1-10(2)17(20)21-14-9-12-13(23-18(14,3)4)7-5-11-6-8-15(19)22-16(11)12/h5-8,10,14H,9H2,1-4H3/t14-/m1/s1
SMILES O=C(C(C)C)O[C@@H]1Cc2c(OC1(C)C)ccc1c2oc(=O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.13 Volume:   322.347
?
Van der Waals volume.
Dense:   0.981 LogP:   3.544
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.313
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.707
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   65.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

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:   3.302 Fsp3:   0.444
MCE-18:   64.615
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.346 Fluc inhibitor:   0.153
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.993
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.44
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.338 Promiscuous compounds:   0.065

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.576 MDCK Permeability:   -4.675
Pgp-inhibitor:   0.298 Pgp-substrate:   0.0
PAMPA:   0.146
?
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):   0.0
20% Bioavailability (F20%):   0.923 30% Bioavailability (F30%):   0.877
50% Bioavailability (F50%):   0.899

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.999
Plasma Protein Binding (PPB):   94.374% Volume Distribution (VD):   -0.016
Fu: 5.836%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.66 CYP1A2-substrate:   0.894
CYP2C19-inhibitor:   0.557 CYP2C19-substrate:   0.085
CYP2C9-inhibitor:   0.959 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.979
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.869
CYP2B6-substrate:   0.984 CYP2C8-inhibitor:   0.993
HLM stability:   0.933
?
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):  6.714 Half-life (T1/2):  0.456

ADMET: Toxicity

hERG Blockers:  0.138 hERG Blockers (10um):  0.383
Human Hepatotoxicity (H-HT):  0.637 Drug-induced Liver Injury (DILI):  0.946
AMES Toxicity:  0.592 Rat Oral Acute Toxicity:  0.647
Maximum Recommended Daily Dose:  0.654 Skin Sensitization:  0.687
Carcinogencity:  0.665 Eye Corrosion:  0.376
Eye Irritation:  0.933 Respiratory Toxicity:  0.867
Drug-induced Neurotoxicity:  0.468 Ototoxicity:  0.317
Hematotoxicity:  0.265 Drug-induced Nephrotoxicity:  0.51
Genotoxicity:  0.887 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.157 Hek293 Cytotoxicity:  0.327
BCF:   1.445
?
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:   4.154
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.928
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.468
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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
NPO32915 prionosciadium watsoni Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[12088423]

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
NPT886 Cell line NIH3T3 Mus musculus Activity = 31.31 % PMID[28571822]
NPT886 Cell line NIH3T3 Mus musculus Activity = 25.89 % PMID[28571822]
NPT886 Cell line NIH3T3 Mus musculus Activity = 19.53 % PMID[28571822]
NPT886 Cell line NIH3T3 Mus musculus Activity = 8.13 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 100.08 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 101.3 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 110.34 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 147.43 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 28.99 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 23.78 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 18.04 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Activity = 7.64 % PMID[28571822]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 23.52 % PMID[17043131]
NPT965 Organism Amaranthus hypochondriacus Amaranthus hypochondriacus IC50 = 237000.0 nM PMID[23411074]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli IC50 = 169000.0 nM PMID[18358571]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 19.59 % PMID[27128177]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 58.81 % PMID[25798528]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 100.0 % PMID[7673938]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 20.0 % PMID[18052029]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 54.3 % PMID[27155463]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 84.92 % DOI[10.1039/C5MD00429B]
NPT854 Organism Lemna paucicostata Lemna paucicostata GI = 87.38 % PMID[27387356]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT886 Cell line NIH3T3 Mus musculus Survival = 45.72 % PMID[28571822]
NPT886 Cell line NIH3T3 Mus musculus Survival = 55.6 % PMID[28571822]
NPT886 Cell line NIH3T3 Mus musculus Survival = 67.43 % PMID[28571822]
NPT886 Cell line NIH3T3 Mus musculus Survival = 83.14 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Survival = 44.77 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Survival = 56.11 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Survival = 66.48 % PMID[28571822]
NPT20904 Cell line Hep 3B2 Homo sapiens Survival = 82.32 % PMID[28571822]





 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 NPC281241 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 NPC472424
0.7797 Intermediate Similarity NPC260265
0.6786 Remote Similarity NPC80170
0.6308 Remote Similarity NPC471909
0.6232 Remote Similarity NPC87950
0.6061 Remote Similarity NPC86892
0.6 Remote Similarity NPC33986
0.5833 Remote Similarity NPC104796
0.5781 Remote Similarity NPC167111
0.5781 Remote Similarity NPC318400
0.5738 Remote Similarity NPC188380
0.5738 Remote Similarity NPC224543
0.5672 Remote Similarity NPC55149
0.5571 Remote Similarity NPC476455
0.5556 Remote Similarity NPC471625
0.5469 Remote Similarity NPC168710
0.5441 Remote Similarity NPC476457
0.5429 Remote Similarity NPC149320
0.5429 Remote Similarity NPC160727
0.5429 Remote Similarity NPC177281
0.541 Remote Similarity NPC55147
0.5362 Remote Similarity NPC119640
0.5362 Remote Similarity NPC166672
0.5362 Remote Similarity NPC183646
0.5352 Remote Similarity NPC128529
0.5352 Remote Similarity NPC55615
0.5286 Remote Similarity NPC195357
0.5286 Remote Similarity NPC152771
0.5217 Remote Similarity NPC287286
0.5211 Remote Similarity NPC195343
0.5211 Remote Similarity NPC267412
0.5211 Remote Similarity NPC207002
0.5211 Remote Similarity NPC133956
0.5211 Remote Similarity NPC47163
0.5211 Remote Similarity NPC74655
0.5211 Remote Similarity NPC471910
0.5161 Remote Similarity NPC96286
0.5139 Remote Similarity NPC84894
0.5139 Remote Similarity NPC18804
0.5139 Remote Similarity NPC319859
0.5139 Remote Similarity NPC296624
0.5139 Remote Similarity NPC164269
0.5139 Remote Similarity NPC198381
0.5139 Remote Similarity NPC287182
0.5139 Remote Similarity NPC127888
0.5132 Remote Similarity NPC471630

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC281241 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