Natural Product: NPC224543

Natural Product IDNPC224543
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (+)-Lomatin
IUPAC Name (9R)-9-hydroxy-8,8-dimethyl-9,10-dihydropyrano[2,3-h]chromen-2-one
Synonyms (+)-Lomatin; Lomatin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL503137
PubChem CID 759302
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 UJSHBYQGQRPVNO-LLVKDONJSA-N
Standard InCHI InChI=1S/C14H14O4/c1-14(2)11(15)7-9-10(18-14)5-3-8-4-6-12(16)17-13(8)9/h3-6,11,15H,7H2,1-2H3/t11-/m1/s1
SMILES O=c1ccc2c(o1)c1C[C@@H](O)C(Oc1cc2)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.09 Volume:   247.009
?
Van der Waals volume.
Dense:   0.996 LogP:   1.972
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.825
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.506
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.721 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.198 Fsp3:   0.357
MCE-18:   59.684
?
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:   0.493 Fluc inhibitor:   0.152
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.996
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.313
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.334 Promiscuous compounds:   0.25

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.699 MDCK Permeability:   -4.579
Pgp-inhibitor:   0.002 Pgp-substrate:   0.001
PAMPA:   0.789
?
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):   0.002
20% Bioavailability (F20%):   0.85 30% Bioavailability (F30%):   0.886
50% Bioavailability (F50%):   0.721

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.993
Plasma Protein Binding (PPB):   91.071% Volume Distribution (VD):   -0.146
Fu: 8.218%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.403
CYP2C19-inhibitor:   0.194 CYP2C19-substrate:   0.047
CYP2C9-inhibitor:   0.38 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.025 CYP2D6-substrate:   0.317
CYP3A4-inhibitor:   0.923 CYP3A4-substrate:   0.262
CYP2B6-substrate:   0.083 CYP2C8-inhibitor:   0.977
HLM stability:   0.951
?
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):  10.845 Half-life (T1/2):  1.193

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.325
Human Hepatotoxicity (H-HT):  0.504 Drug-induced Liver Injury (DILI):  0.569
AMES Toxicity:  0.593 Rat Oral Acute Toxicity:  0.387
Maximum Recommended Daily Dose:  0.76 Skin Sensitization:  0.413
Carcinogencity:  0.799 Eye Corrosion:  0.238
Eye Irritation:  0.972 Respiratory Toxicity:  0.645
Drug-induced Neurotoxicity:  0.193 Ototoxicity:  0.267
Hematotoxicity:  0.225 Drug-induced Nephrotoxicity:  0.381
Genotoxicity:  0.604 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.187
BCF:   0.402
?
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:   3.07
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.517
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.824
?
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
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[11374978]
NPO32915 prionosciadium watsoni Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[12088423]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[15679317]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[17997069]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6800 Libanotis buchtormensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16614 Zanthoxylum spinosum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6444 Humulus scandens Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1821 Kopsia albiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2741 Ribes sanguineum Species Grossulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5497 Stachys chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14809 Talaromyces avellaneus Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14108 Nardostachys jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6800 Libanotis buchtormensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14108 Nardostachys jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14108 Nardostachys jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6800 Libanotis buchtormensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14108 Nardostachys jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14108 Nardostachys jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6444 Humulus scandens Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5497 Stachys chinensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1821 Kopsia albiflora Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14809 Talaromyces avellaneus Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16614 Zanthoxylum spinosum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14108 Nardostachys jatamansi Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6800 Libanotis buchtormensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2741 Ribes sanguineum Species Grossulariaceae 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
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT54 Individual protein Nonstructural protein 1 Influenza A virus Potency = 4466.8 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 22387.2 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 10417.9 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT965 Organism Amaranthus hypochondriacus Amaranthus hypochondriacus IC50 = 344000.0 nM PMID[12088423]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli IC50 = 296000.0 nM PMID[12088423]
NPT2 Others Unspecified n.a. Potency = 25929.0 nM PubChem BioAssay data set

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 NPC224543 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 NPC188380
0.7308 Intermediate Similarity NPC62366
0.6897 Remote Similarity NPC479311
0.6792 Remote Similarity NPC225106
0.6792 Remote Similarity NPC184861
0.6792 Remote Similarity NPC281014
0.6792 Remote Similarity NPC212124
0.6792 Remote Similarity NPC294456
0.6491 Remote Similarity NPC479313
0.6481 Remote Similarity NPC104796
0.6364 Remote Similarity NPC185066
0.6296 Remote Similarity NPC80170
0.6207 Remote Similarity NPC153818
0.6207 Remote Similarity NPC232246
0.6129 Remote Similarity NPC479310
0.6071 Remote Similarity NPC33986
0.6 Remote Similarity NPC55147
0.6 Remote Similarity NPC96286
0.5965 Remote Similarity NPC78746
0.5821 Remote Similarity NPC87950
0.5763 Remote Similarity NPC168710
0.5738 Remote Similarity NPC472424
0.5738 Remote Similarity NPC281241
0.5714 Remote Similarity NPC287286
0.5645 Remote Similarity NPC479309
0.5645 Remote Similarity NPC479312
0.5614 Remote Similarity NPC50896
0.5614 Remote Similarity NPC326600
0.5538 Remote Similarity NPC479308
0.5469 Remote Similarity NPC260265
0.5455 Remote Similarity NPC312881
0.5397 Remote Similarity NPC472525
0.5345 Remote Similarity NPC13007
0.5345 Remote Similarity NPC229916
0.5345 Remote Similarity NPC610664
0.5286 Remote Similarity NPC471764
0.5238 Remote Similarity NPC26954
0.5238 Remote Similarity NPC38099
0.5167 Remote Similarity NPC213173
0.5082 Remote Similarity NPC31849
0.5082 Remote Similarity NPC85085

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC224543 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