Natural Product: NPC21184

Natural Product IDNPC21184
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Cleomiscosin D
IUPAC Name (2S,3S)-2-(4-hydroxy-3,5-dimethoxyphenyl)-3-(hydroxymethyl)-5-methoxy-2,3-dihydropyrano[3,2-h][1,4]benzodioxin-9-one
Synonyms Cleomiscosin D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL256915
PubChem CID 13965876
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0002545] Coumarinolignans

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 IXSZNNRKGDOXQI-YJBOKZPZSA-N
Standard InCHI InChI=1S/C21H20O9/c1-25-12-7-11(8-13(26-2)17(12)24)18-15(9-22)28-20-14(27-3)6-10-4-5-16(23)29-19(10)21(20)30-18/h4-8,15,18,22,24H,9H2,1-3H3/t15-,18-/m0/s1
SMILES COc1cc(cc(c1O)OC)[C@H]1[C@H](CO)Oc2c(cc3ccc(=O)oc3c2O1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.11 Volume:   395.567
?
Van der Waals volume.
Dense:   1.052 LogP:   1.882
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.176
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.152
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   23.0
TPSA:   116.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.605 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.511 Fsp3:   0.286
MCE-18:   75.556
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.468 Fluc inhibitor:   0.591
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.792
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.455
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.153 Promiscuous compounds:   0.566

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.57 MDCK Permeability:   -5.001
Pgp-inhibitor:   0.021 Pgp-substrate:   0.001
PAMPA:   0.058
?
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):   0.007
20% Bioavailability (F20%):   0.234 30% Bioavailability (F30%):   0.214
50% Bioavailability (F50%):   0.65

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.99
Plasma Protein Binding (PPB):   92.084% Volume Distribution (VD):   -0.224
Fu: 6.769%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.004
BSEP inhibitor:   0.95

ADMET: Metabolism

CYP1A2-inhibitor:   0.991 CYP1A2-substrate:   0.106
CYP2C19-inhibitor:   0.982 CYP2C19-substrate:   0.165
CYP2C9-inhibitor:   0.772 CYP2C9-substrate:   0.405
CYP2D6-inhibitor:   0.072 CYP2D6-substrate:   0.938
CYP3A4-inhibitor:   0.171 CYP3A4-substrate:   0.959
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   0.82
HLM stability:   0.282
?
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):  7.138 Half-life (T1/2):  1.721

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.244
Human Hepatotoxicity (H-HT):  0.716 Drug-induced Liver Injury (DILI):  0.797
AMES Toxicity:  0.464 Rat Oral Acute Toxicity:  0.44
Maximum Recommended Daily Dose:  0.385 Skin Sensitization:  0.704
Carcinogencity:  0.689 Eye Corrosion:  0.007
Eye Irritation:  0.744 Respiratory Toxicity:  0.309
Drug-induced Neurotoxicity:  0.525 Ototoxicity:  0.412
Hematotoxicity:  0.482 Drug-induced Nephrotoxicity:  0.445
Genotoxicity:  0.828 RPMI-8226 Immunitoxicity:  0.208
A549 Cytotoxicity:  0.195 Hek293 Cytotoxicity:  0.325
BCF:   0.857
?
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:   3.471
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.729
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.018
?
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
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota root bark n.a. n.a. PMID[10346965]
NPO28941 Pogonopus speciosus Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[10514334]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. root n.a. PMID[10617409]
NPO28697 Talaromyces convolutus Species Trichocomaceae Eukaryota n.a. n.a. n.a. PMID[10869198]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[11575966]
NPO18723 Zanthoxylum avicennae Species Rutaceae Eukaryota stem wood Pakuashan, Changhua County, Taiwan 2006-Jun PMID[18211005]
NPO28941 Pogonopus speciosus Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[1982768]
NPO29000 Nephila clavata Species Nephilidae Eukaryota n.a. n.a. n.a. PMID[21188966]
NPO7348 Streptomyces gannmycicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO28697 Talaromyces convolutus Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28941 Pogonopus speciosus Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29000 Nephila clavata Species Nephilidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13983 Acer maximowiczianum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18723 Zanthoxylum avicennae Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29245 Nepeta leucophylla Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18723 Zanthoxylum avicennae Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29245 Nepeta leucophylla Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18723 Zanthoxylum avicennae Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16564 Euonymus phellomanus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28835 Gentianella nitida Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13983 Acer maximowiczianum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18723 Zanthoxylum avicennae Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29367 Ormosia excelsa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7348 Streptomyces gannmycicus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO18723 Zanthoxylum avicennae Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29000 Nephila clavata Species Nephilidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13983 Acer maximowiczianum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28697 Talaromyces convolutus Species Trichocomaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28941 Pogonopus speciosus Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29165 Toona febrifuga Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29062 Hibiscus syriacus Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28915 Tephrosia barbigera Species Geometridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10592 Phascolosoma elongatum Species Phascolosomatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29232 Polysiphonia fastigiata Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4154 Cortinarius violaceus Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16564 Euonymus phellomanus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28835 Gentianella nitida Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28890 Geranium sanguineum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29245 Nepeta leucophylla Species Lamiaceae 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
NPT1084 Subcellular Liver microsomes Rattus norvegicus IC50 = 5.5 ug.mL-1 PMID[11575966]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 50000.0 nM PMID[18211005]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 13080.0 nM PMID[18211005]

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 NPC21184 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
0.873 High Similarity NPC205727
0.8387 Intermediate Similarity NPC15577
0.7576 Intermediate Similarity NPC187398
0.7313 Intermediate Similarity NPC176903
0.7183 Intermediate Similarity NPC120426
0.7 Intermediate Similarity NPC485419
0.7 Intermediate Similarity NPC485418
0.6301 Remote Similarity NPC476348
0.6216 Remote Similarity NPC476347
0.5976 Remote Similarity NPC142614
0.5867 Remote Similarity NPC294522
0.5488 Remote Similarity NPC30688
0.5246 Remote Similarity NPC244799
0.5176 Remote Similarity NPC215060
0.5132 Remote Similarity NPC485421
0.5132 Remote Similarity NPC485417
0.5132 Remote Similarity NPC485416
0.5132 Remote Similarity NPC485420
0.5114 Remote Similarity NPC120774

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC21184 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