Natural Product: NPC494385

Natural Product IDNPC494385
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-hydroxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)-3-[(2~{S},3~{S},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name 5-hydroxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)-3-[(2~{S},3~{S},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-[[(2~{R},3~{R},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 DTSVAGTXAHLUAU-PBRLYLEESA-N
Standard InCHI InChI=1S/C33H40O22/c1-8-18(38)23(43)26(46)31(50-8)49-7-16-21(41)25(45)28(48)33(54-16)55-30-22(42)17-11(35)4-10(51-32-27(47)24(44)20(40)15(6-34)53-32)5-14(17)52-29(30)9-2-12(36)19(39)13(37)3-9/h2-5,8,15-16,18,20-21,23-28,31-41,43-48H,6-7H2,1H3/t8-,15+,16+,18-,20+,21+,23-,24-,25+,26+,27+,28-,31+,32+,33-/m0/s1
SMILES C[C@@H]1O[C@@H](OC[C@H]2O[C@@H](OC3=C(C4=CC(O)=C(O)C(O)=C4)OC4=CC(O[C@@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)=CC(O)=C4C3=O)[C@@H](O)[C@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   788.2 Volume:   700.279
?
Van der Waals volume.
Dense:   1.126 LogP:   -0.942
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.468
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.186
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   36.0
TPSA:   368.81
?
Topological Polar Surface Area.
 H-Bond Acceptor:   22.0
H-Bond Donor:   14.0 Rings:   6.0
Heavy Atoms:   22.0

MedChem Properties

QED Drug-Likeness Score:   0.091 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.494 Fsp3:   0.545
MCE-18:   157.882
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.649 Fluc inhibitor:   0.182
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.798
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.648
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.225 Promiscuous compounds:   0.624

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.801 MDCK Permeability:   -4.884
Pgp-inhibitor:   0.0 Pgp-substrate:   0.921
PAMPA:   1.0
?
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):   0.995
20% Bioavailability (F20%):   0.759 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.006
Plasma Protein Binding (PPB):   72.368% Volume Distribution (VD):   -0.163
Fu: 27.005%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.072
BSEP inhibitor:   0.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.005
?
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):  0.638 Half-life (T1/2):  6.9

ADMET: Toxicity

hERG Blockers:  0.003 hERG Blockers (10um):  0.22
Human Hepatotoxicity (H-HT):  0.391 Drug-induced Liver Injury (DILI):  0.969
AMES Toxicity:  0.926 Rat Oral Acute Toxicity:  0.002
Maximum Recommended Daily Dose:  0.01 Skin Sensitization:  1.0
Carcinogencity:  0.007 Eye Corrosion:  0.0
Eye Irritation:  0.014 Respiratory Toxicity:  0.0
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  1.0
Hematotoxicity:  0.018 Drug-induced Nephrotoxicity:  0.394
Genotoxicity:  0.851 RPMI-8226 Immunitoxicity:  0.026
A549 Cytotoxicity:  0.939 Hek293 Cytotoxicity:  0.132
BCF:   0.271
?
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:   2.79
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.617
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.597
?
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
NPO49435 Limnanthes douglasii Species Limnanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC494385 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
0.7753 Intermediate Similarity NPC186816
0.7708 Intermediate Similarity NPC480441
0.7528 Intermediate Similarity NPC39834
0.7528 Intermediate Similarity NPC275454
0.7528 Intermediate Similarity NPC227508
0.7381 Intermediate Similarity NPC158674
0.7356 Intermediate Similarity NPC605784
0.7347 Intermediate Similarity NPC25523
0.6977 Remote Similarity NPC136042
0.6966 Remote Similarity NPC116458
0.6966 Remote Similarity NPC246943
0.6957 Remote Similarity NPC67105
0.6939 Remote Similarity NPC14187
0.6882 Remote Similarity NPC210073
0.6739 Remote Similarity NPC251417
0.6702 Remote Similarity NPC203259
0.6702 Remote Similarity NPC33054
0.6702 Remote Similarity NPC176740
0.6702 Remote Similarity NPC471725
0.6702 Remote Similarity NPC134532
0.6702 Remote Similarity NPC156869
0.6702 Remote Similarity NPC602582
0.6667 Remote Similarity NPC289667
0.6667 Remote Similarity NPC470443
0.6591 Remote Similarity NPC297987
0.6517 Remote Similarity NPC84362
0.6517 Remote Similarity NPC271692
0.6465 Remote Similarity NPC473073
0.6421 Remote Similarity NPC173582
0.6421 Remote Similarity NPC44931
0.6421 Remote Similarity NPC265885
0.6421 Remote Similarity NPC181465
0.6421 Remote Similarity NPC215710
0.6421 Remote Similarity NPC473438
0.6421 Remote Similarity NPC253788
0.6392 Remote Similarity NPC488073
0.6392 Remote Similarity NPC126784
0.6392 Remote Similarity NPC241423
0.6383 Remote Similarity NPC480463
0.6354 Remote Similarity NPC22062
0.6354 Remote Similarity NPC65563
0.6354 Remote Similarity NPC473634
0.6354 Remote Similarity NPC470949
0.6354 Remote Similarity NPC138811
0.6292 Remote Similarity NPC19388
0.6292 Remote Similarity NPC240431
0.6292 Remote Similarity NPC249281
0.6292 Remote Similarity NPC55786
0.6263 Remote Similarity NPC32641
0.6263 Remote Similarity NPC256188
0.6263 Remote Similarity NPC209296
0.6263 Remote Similarity NPC35119
0.625 Remote Similarity NPC292019
0.625 Remote Similarity NPC202908
0.62 Remote Similarity NPC142142
0.617 Remote Similarity NPC276377
0.6154 Remote Similarity NPC46420
0.6132 Remote Similarity NPC277532
0.61 Remote Similarity NPC473327
0.604 Remote Similarity NPC486577
0.6022 Remote Similarity NPC611303
0.602 Remote Similarity NPC150164
0.6 Remote Similarity NPC473043
0.6 Remote Similarity NPC135599
0.6 Remote Similarity NPC73855
0.6 Remote Similarity NPC113968
0.6 Remote Similarity NPC328940
0.6 Remote Similarity NPC189564
0.6 Remote Similarity NPC277174
0.6 Remote Similarity NPC606877
0.598 Remote Similarity NPC476472
0.598 Remote Similarity NPC294815
0.598 Remote Similarity NPC16194
0.596 Remote Similarity NPC473571
0.596 Remote Similarity NPC110941
0.5905 Remote Similarity NPC203145
0.59 Remote Similarity NPC240306
0.59 Remote Similarity NPC64425
0.587 Remote Similarity NPC277205
0.587 Remote Similarity NPC37919
0.5865 Remote Similarity NPC135358
0.5806 Remote Similarity NPC349108
0.5758 Remote Similarity NPC67326
0.5714 Remote Similarity NPC602448
0.57 Remote Similarity NPC479405
0.57 Remote Similarity NPC303913
0.5699 Remote Similarity NPC189142
0.5699 Remote Similarity NPC77660
0.5686 Remote Similarity NPC65711
0.5686 Remote Similarity NPC479403
0.567 Remote Similarity NPC355481
0.5657 Remote Similarity NPC480466
0.5644 Remote Similarity NPC479404
0.5631 Remote Similarity NPC72016
0.5607 Remote Similarity NPC121703
0.5604 Remote Similarity NPC34531
0.5591 Remote Similarity NPC238376
0.5565 Remote Similarity NPC192539
0.5545 Remote Similarity NPC311850
0.5532 Remote Similarity NPC145038
0.5532 Remote Similarity NPC56077
0.5532 Remote Similarity NPC281131
0.5532 Remote Similarity NPC253662
0.5532 Remote Similarity NPC179950
0.5532 Remote Similarity NPC88789
0.5532 Remote Similarity NPC491374
0.5521 Remote Similarity NPC488071
0.55 Remote Similarity NPC471079
0.5487 Remote Similarity NPC198199
0.5481 Remote Similarity NPC122467
0.5481 Remote Similarity NPC606657
0.5455 Remote Similarity NPC116864
0.5455 Remote Similarity NPC244776
0.5437 Remote Similarity NPC488074
0.5426 Remote Similarity NPC261866
0.5426 Remote Similarity NPC19709
0.5398 Remote Similarity NPC68592
0.5377 Remote Similarity NPC89127
0.5368 Remote Similarity NPC64305
0.5368 Remote Similarity NPC323593
0.5368 Remote Similarity NPC203500
0.5361 Remote Similarity NPC285197
0.5351 Remote Similarity NPC298666
0.5347 Remote Similarity NPC187379
0.5345 Remote Similarity NPC120952
0.534 Remote Similarity NPC204693
0.534 Remote Similarity NPC115674
0.5333 Remote Similarity NPC473623
0.5327 Remote Similarity NPC101636
0.5312 Remote Similarity NPC27640
0.5294 Remote Similarity NPC267680
0.5283 Remote Similarity NPC488089
0.5278 Remote Similarity NPC470446
0.5263 Remote Similarity NPC127546
0.5263 Remote Similarity NPC39360
0.5263 Remote Similarity NPC57625
0.5263 Remote Similarity NPC77672
0.5263 Remote Similarity NPC133671
0.5263 Remote Similarity NPC135391
0.5263 Remote Similarity NPC29763
0.5263 Remote Similarity NPC173637
0.5263 Remote Similarity NPC78263
0.5263 Remote Similarity NPC210003
0.5263 Remote Similarity NPC317489
0.5263 Remote Similarity NPC250069
0.5263 Remote Similarity NPC223424
0.5263 Remote Similarity NPC600591
0.5258 Remote Similarity NPC42773
0.5258 Remote Similarity NPC472459
0.5258 Remote Similarity NPC45522
0.5258 Remote Similarity NPC599850
0.5243 Remote Similarity NPC293626
0.5243 Remote Similarity NPC605592
0.5238 Remote Similarity NPC12013
0.5238 Remote Similarity NPC11432
0.5238 Remote Similarity NPC477613
0.5221 Remote Similarity NPC470716
0.5214 Remote Similarity NPC209550
0.5208 Remote Similarity NPC95090
0.5208 Remote Similarity NPC27408
0.5189 Remote Similarity NPC229409
0.5185 Remote Similarity NPC470445
0.5182 Remote Similarity NPC11468
0.5179 Remote Similarity NPC470715
0.5179 Remote Similarity NPC303694
0.5179 Remote Similarity NPC164704
0.5155 Remote Similarity NPC24043
0.5152 Remote Similarity NPC22832
0.5152 Remote Similarity NPC486578
0.5146 Remote Similarity NPC471748
0.5128 Remote Similarity NPC488078
0.5126 Remote Similarity NPC262222
0.5122 Remote Similarity NPC223860
0.5104 Remote Similarity NPC108831
0.5104 Remote Similarity NPC182634
0.5102 Remote Similarity NPC59534
0.5102 Remote Similarity NPC325555
0.5102 Remote Similarity NPC226304
0.5096 Remote Similarity NPC155877
0.5096 Remote Similarity NPC102028
0.5093 Remote Similarity NPC475382
0.5093 Remote Similarity NPC76831
0.5091 Remote Similarity NPC244875
0.5085 Remote Similarity NPC138990
0.5052 Remote Similarity NPC265530
0.5051 Remote Similarity NPC60735
0.5051 Remote Similarity NPC307938
0.5051 Remote Similarity NPC26230
0.5049 Remote Similarity NPC29958
0.5049 Remote Similarity NPC609888
0.5047 Remote Similarity NPC37668
0.5046 Remote Similarity NPC292929
0.5046 Remote Similarity NPC287889
0.5046 Remote Similarity NPC221342
0.5046 Remote Similarity NPC476470

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC494385 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
0.7717 Intermediate Similarity NPD7251 Phase 2
0.7041 Intermediate Similarity NPD7808 Phase 3
0.6702 Remote Similarity NPD6797 Phase 2
0.6263 Remote Similarity NPD7054 Phase 4
0.5045 Remote Similarity NPD7472 Pre-clinical

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