Natural Product: NPC189095

Natural Product IDNPC189095
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HWQSPRJGHSGSPF-OIQJVACTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0000358] Furanocoumarins
          • [CHEMONTID:0002569] Linear furanocoumarins
            • [CHEMONTID:0000202] Psoralens

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 HWQSPRJGHSGSPF-OIQJVACTSA-N
Standard InCHI InChI=1S/C21H24O6/c1-13(4-6-16(22)21(2,3)24)8-10-26-20-18-15(9-11-25-18)12-14-5-7-17(23)27-19(14)20/h5,7-9,11-12,16,22,24H,4,6,10H2,1-3H3/b13-8+/t16-/m0/s1
SMILES C/C(=CCOc1c2c(cco2)cc2ccc(=O)oc12)/CC[C@@H](C(C)(C)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.16 Volume:   380.389
?
Van der Waals volume.
Dense:   0.978 LogP:   3.379
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.17
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.497
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   17.0
TPSA:   93.04
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.484 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.523 Fsp3:   0.381
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:   0.552 Fluc inhibitor:   0.275
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.963
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.224
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.037 Promiscuous compounds:   0.204

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.713 MDCK Permeability:   -4.549
Pgp-inhibitor:   0.0 Pgp-substrate:   0.002
PAMPA:   0.378
?
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%):   0.982 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.542
Plasma Protein Binding (PPB):   94.501% Volume Distribution (VD):   -0.101
Fu: 4.145%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.105
BSEP inhibitor:   0.013

ADMET: Metabolism

CYP1A2-inhibitor:   0.558 CYP1A2-substrate:   0.956
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.206
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.984 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  10.732 Half-life (T1/2):  0.777

ADMET: Toxicity

hERG Blockers:  0.34 hERG Blockers (10um):  0.43
Human Hepatotoxicity (H-HT):  0.67 Drug-induced Liver Injury (DILI):  0.591
AMES Toxicity:  0.362 Rat Oral Acute Toxicity:  0.489
Maximum Recommended Daily Dose:  0.892 Skin Sensitization:  0.358
Carcinogencity:  0.685 Eye Corrosion:  0.0
Eye Irritation:  0.239 Respiratory Toxicity:  0.822
Drug-induced Neurotoxicity:  0.229 Ototoxicity:  0.391
Hematotoxicity:  0.299 Drug-induced Nephrotoxicity:  0.421
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.095 Hek293 Cytotoxicity:  0.388
BCF:   0.962
?
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:   3.556
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.176
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.466
?
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
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. DOI[10.3390/plants9101397]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. seed n.a. PMID[10075120]
NPO7344 Spiraea prunifolia Species Rosaceae Eukaryota n.a. n.a. n.a. PMID[11473429]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. PMID[16499335]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[17228877]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[18484537]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[19615910]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[29323912]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. root n.a. PMID[731398]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[731398]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. rhizome n.a. PMID[7714541]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. PMID[7760071]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. rhizome n.a. PMID[7798964]
NPO19895 Plectranthus hereroensis Species Lamiaceae Eukaryota Roots n.a. n.a. PMID[7931371]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. PMID[7964801]
NPO23356 Ascodesmis sphaerospora Species Ascodesmidaceae Eukaryota n.a. n.a. n.a. PMID[9868168]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23588 Ursinia anthemoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23490 Dalbergia monetaria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23398 Caralluma russeliana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7344 Spiraea prunifolia Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23588 Ursinia anthemoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23628 Imperata cylindrica Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9814 Lactarius fuliginosus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23588 Ursinia anthemoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17492 Amomum reticulatum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23356 Ascodesmis sphaerospora Species Ascodesmidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19895 Plectranthus hereroensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23822 Polypodium aureum Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24396 Grosvenoria rimbachii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO15572 Espeletiopsis purpurascens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23398 Caralluma russeliana Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23911 Alpinia officinarum Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24280 Helianthus californicus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24038 Casimiroa edulis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23490 Dalbergia monetaria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7344 Spiraea prunifolia Species Rosaceae 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

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 NPC189095 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
0.7692 Intermediate Similarity NPC216092
0.7377 Intermediate Similarity NPC243509
0.6984 Remote Similarity NPC51404
0.6984 Remote Similarity NPC83421
0.6719 Remote Similarity NPC215722
0.65 Remote Similarity NPC487850
0.6486 Remote Similarity NPC478632
0.64 Remote Similarity NPC478631
0.6216 Remote Similarity NPC49009
0.5915 Remote Similarity NPC113098
0.589 Remote Similarity NPC478569
0.5735 Remote Similarity NPC173149
0.5735 Remote Similarity NPC179015
0.5735 Remote Similarity NPC602724
0.5645 Remote Similarity NPC33320
0.5541 Remote Similarity NPC478566
0.5526 Remote Similarity NPC193881
0.5467 Remote Similarity NPC478570
0.5455 Remote Similarity NPC267336
0.5455 Remote Similarity NPC272650
0.5211 Remote Similarity NPC155264
0.5139 Remote Similarity NPC210460
0.5062 Remote Similarity NPC14822

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC189095 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
0.5645 Remote Similarity NPD919 Phase 4

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