Natural Product: NPC22149

Natural Product IDNPC22149
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl (1S)-7-(Hydroxymethyl)-1-[(2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(Hydroxymethyl)Oxan-2-Yl]Oxy-1,4A,5,7A-Tetrahydrocyclopenta[C]Pyran-4-Carboxylate
IUPAC Name methyl (1S)-7-(hydroxymethyl)-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1718933
PubChem CID 16760120
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0002049] Terpene glycosides
          • [CHEMONTID:0004081] Iridoid O-glycosides

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 IBFYXTRXDNAPMM-QZTNVZDFSA-N
Standard InCHI InChI=1S/C17H24O10/c1-24-15(23)9-6-25-16(11-7(4-18)2-3-8(9)11)27-17-14(22)13(21)12(20)10(5-19)26-17/h2,6,8,10-14,16-22H,3-5H2,1H3/t8?,10-,11?,12-,13+,14-,16+,17+/m1/s1
SMILES OC[C@H]1O[C@@H](O[C@@H]2OC=C(C3C2C(=CC3)CO)C(=O)OC)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   388.14 Volume:   356.912
?
Van der Waals volume.
Dense:   1.087 LogP:   -0.719
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.294
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.099
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   155.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.258 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.635 Fsp3:   0.706
MCE-18:   52.414
?
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:   0.222 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.085
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.275 Promiscuous compounds:   0.019

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.518 MDCK Permeability:   -5.065
Pgp-inhibitor:   0.0 Pgp-substrate:   0.251
PAMPA:   0.989
?
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):   0.693
20% Bioavailability (F20%):   0.218 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.909

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.039 MRP1:   0.745
Plasma Protein Binding (PPB):   38.634% Volume Distribution (VD):   -0.535
Fu: 60.338%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.967
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.022
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.065
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.804
HLM stability:   0.161
?
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):  1.861 Half-life (T1/2):  2.797

ADMET: Toxicity

hERG Blockers:  0.013 hERG Blockers (10um):  0.086
Human Hepatotoxicity (H-HT):  0.664 Drug-induced Liver Injury (DILI):  0.943
AMES Toxicity:  0.841 Rat Oral Acute Toxicity:  0.055
Maximum Recommended Daily Dose:  0.041 Skin Sensitization:  0.979
Carcinogencity:  0.207 Eye Corrosion:  0.0
Eye Irritation:  0.026 Respiratory Toxicity:  0.017
Drug-induced Neurotoxicity:  0.027 Ototoxicity:  0.991
Hematotoxicity:  0.308 Drug-induced Nephrotoxicity:  0.529
Genotoxicity:  0.456 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.16
BCF:   0.312
?
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:   2.931
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.634
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.592
?
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
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota Fruits n.a. n.a. PMID[16309325]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. Seoul, Korea 2000-Jun PMID[16643034]
NPO10008 Tinospora capillipes Species Menispermaceae Eukaryota n.a. root n.a. PMID[17340259]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[18505286]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota fruit n.a. n.a. PMID[19650637]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota fruits n.a. n.a. PMID[23305920]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. PMID[2488968]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. seed n.a. PMID[2610694]
NPO8918 Plantago depressa Species Plantaginaceae Eukaryota n.a. n.a. n.a. PMID[26562611]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. bark n.a. PMID[26767291]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. PMID[26767291]
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[28836430]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota Fruits n.a. n.a. PMID[29140705]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[32141747]
NPO8918 Plantago depressa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10008 Tinospora capillipes Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8918 Plantago depressa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10008 Tinospora capillipes Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10008 Tinospora capillipes Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8918 Plantago depressa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8918 Plantago depressa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8918 Plantago depressa Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10008 Tinospora capillipes Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16850 Eucommia ulmoides Species Eucommiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10008 Tinospora capillipes Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12588 Cornus officinalis Species Cornaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9518 Gardenia jasminoides Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25734 Tinospora sagittata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3477 Plantago asiatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8918 Plantago depressa Species Plantaginaceae 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
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 73.1 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 23099.9 nM PubChem BioAssay data set

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 NPC22149 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 NPC255677
1.0 High Similarity NPC306344
0.85 High Similarity NPC197541
0.85 High Similarity NPC234304
0.85 High Similarity NPC118761
0.7833 Intermediate Similarity NPC222062
0.7368 Intermediate Similarity NPC482656
0.7231 Intermediate Similarity NPC267869
0.7231 Intermediate Similarity NPC284929
0.7015 Intermediate Similarity NPC86095
0.7 Intermediate Similarity NPC298255
0.6833 Remote Similarity NPC474730
0.6833 Remote Similarity NPC117596
0.6721 Remote Similarity NPC35185
0.6721 Remote Similarity NPC4899
0.6721 Remote Similarity NPC177013
0.6508 Remote Similarity NPC27687
0.6508 Remote Similarity NPC37240
0.6452 Remote Similarity NPC250545
0.6406 Remote Similarity NPC231710
0.6406 Remote Similarity NPC470573
0.6406 Remote Similarity NPC120021
0.6406 Remote Similarity NPC216826
0.6406 Remote Similarity NPC270908
0.6406 Remote Similarity NPC65665
0.625 Remote Similarity NPC106668
0.6212 Remote Similarity NPC488472
0.6212 Remote Similarity NPC257424
0.619 Remote Similarity NPC307699
0.619 Remote Similarity NPC475928
0.6119 Remote Similarity NPC41681
0.6094 Remote Similarity NPC148270
0.6032 Remote Similarity NPC170432
0.6 Remote Similarity NPC220167
0.6 Remote Similarity NPC61201
0.5938 Remote Similarity NPC195510
0.5938 Remote Similarity NPC13171
0.5821 Remote Similarity NPC475851
0.5821 Remote Similarity NPC475924
0.5694 Remote Similarity NPC488456
0.5694 Remote Similarity NPC488471
0.5694 Remote Similarity NPC488466
0.5694 Remote Similarity NPC488465
0.5694 Remote Similarity NPC488460
0.5694 Remote Similarity NPC488462
0.5672 Remote Similarity NPC193741
0.5663 Remote Similarity NPC69367
0.5663 Remote Similarity NPC611523
0.5634 Remote Similarity NPC605627
0.5616 Remote Similarity NPC488470
0.5588 Remote Similarity NPC609500
0.5541 Remote Similarity NPC488457
0.5541 Remote Similarity NPC488464
0.5541 Remote Similarity NPC488463
0.5538 Remote Similarity NPC303451
0.5538 Remote Similarity NPC72358
0.5507 Remote Similarity NPC254538
0.5429 Remote Similarity NPC310804
0.5429 Remote Similarity NPC261117
0.5373 Remote Similarity NPC241911
0.5294 Remote Similarity NPC110701
0.525 Remote Similarity NPC475213
0.525 Remote Similarity NPC152796
0.519 Remote Similarity NPC46641
0.519 Remote Similarity NPC488467
0.5185 Remote Similarity NPC31745
0.5185 Remote Similarity NPC220936
0.5072 Remote Similarity NPC101051
0.5062 Remote Similarity NPC488468

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC22149 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