Natural Product: NPC497931

Natural Product IDNPC497931
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-3-[(2~{S},3~{R},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-2-[4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]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-3-[(2~{S},3~{R},4~{R},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-2-[4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]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 GZKTYMIMRMNEII-ABIGCIRXSA-N
Standard InCHI InChI=1S/C33H40O21/c34-7-15-19(38)23(42)26(45)31(51-15)48-11-3-1-10(2-4-11)29-30(54-33-28(47)25(44)21(40)17(9-36)53-33)22(41)18-13(37)5-12(6-14(18)50-29)49-32-27(46)24(43)20(39)16(8-35)52-32/h1-6,15-17,19-21,23-28,31-40,42-47H,7-9H2/t15-,16-,17-,19-,20-,21-,23+,24+,25-,26-,27-,28-,31-,32-,33+/m1/s1
SMILES O=C1C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@@H](O)[C@H]2O)=C(C2=CC=C(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)C=C2)OC2=CC(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=CC(O)=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   772.21 Volume:   691.488
?
Van der Waals volume.
Dense:   1.117 LogP:   -0.111
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.809
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.598
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   36.0
TPSA:   348.58
?
Topological Polar Surface Area.
 H-Bond Acceptor:   21.0
H-Bond Donor:   13.0 Rings:   6.0
Heavy Atoms:   21.0

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:   5.259 Fsp3:   0.545
MCE-18:   150.706
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.626 Fluc inhibitor:   0.306
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.682
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.644
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.371 Promiscuous compounds:   0.544

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -7.212 MDCK Permeability:   -4.723
Pgp-inhibitor:   0.0 Pgp-substrate:   0.537
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):   0.994
20% Bioavailability (F20%):   0.011 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.001
Plasma Protein Binding (PPB):   70.513% Volume Distribution (VD):   -0.21
Fu: 25.357%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.013
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:   0.024
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):  0.522 Half-life (T1/2):  7.068

ADMET: Toxicity

hERG Blockers:  0.002 hERG Blockers (10um):  0.005
Human Hepatotoxicity (H-HT):  0.883 Drug-induced Liver Injury (DILI):  0.998
AMES Toxicity:  0.993 Rat Oral Acute Toxicity:  0.0
Maximum Recommended Daily Dose:  0.0 Skin Sensitization:  1.0
Carcinogencity:  0.027 Eye Corrosion:  0.0
Eye Irritation:  0.0 Respiratory Toxicity:  0.0
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  1.0
Hematotoxicity:  0.307 Drug-induced Nephrotoxicity:  0.947
Genotoxicity:  0.631 RPMI-8226 Immunitoxicity:  0.132
A549 Cytotoxicity:  0.32 Hek293 Cytotoxicity:  0.151
BCF:   0.375
?
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:   2.856
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.722
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.51
?
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
NPO59931 Crambe cordifolia Species Brassicaceae 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 NPC497931 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 NPC289667
0.8696 High Similarity NPC297987
0.8429 Intermediate Similarity NPC136042
0.8108 Intermediate Similarity NPC116458
0.8108 Intermediate Similarity NPC246943
0.8026 Intermediate Similarity NPC251417
0.7917 Intermediate Similarity NPC64305
0.7867 Intermediate Similarity NPC605784
0.7808 Intermediate Similarity NPC84362
0.7531 Intermediate Similarity NPC64425
0.7467 Intermediate Similarity NPC472459
0.7297 Intermediate Similarity NPC249281
0.72 Intermediate Similarity NPC95090
0.72 Intermediate Similarity NPC27408
0.7143 Intermediate Similarity NPC611303
0.7033 Intermediate Similarity NPC470716
0.7 Intermediate Similarity NPC470715
0.6941 Remote Similarity NPC35119
0.6923 Remote Similarity NPC277532
0.6923 Remote Similarity NPC285197
0.6883 Remote Similarity NPC46420
0.6883 Remote Similarity NPC24043
0.6842 Remote Similarity NPC77672
0.6842 Remote Similarity NPC133671
0.6842 Remote Similarity NPC135391
0.6842 Remote Similarity NPC78263
0.6842 Remote Similarity NPC250069
0.6835 Remote Similarity NPC22832
0.6753 Remote Similarity NPC277205
0.6753 Remote Similarity NPC37919
0.6753 Remote Similarity NPC189142
0.6753 Remote Similarity NPC77660
0.6744 Remote Similarity NPC32641
0.6744 Remote Similarity NPC256188
0.6709 Remote Similarity NPC60735
0.6709 Remote Similarity NPC26230
0.6709 Remote Similarity NPC488071
0.6702 Remote Similarity NPC295625
0.6667 Remote Similarity NPC271692
0.6667 Remote Similarity NPC276377
0.663 Remote Similarity NPC164704
0.6625 Remote Similarity NPC243930
0.6625 Remote Similarity NPC120099
0.6625 Remote Similarity NPC21666
0.6625 Remote Similarity NPC486578
0.6623 Remote Similarity NPC261866
0.6623 Remote Similarity NPC39360
0.6623 Remote Similarity NPC29763
0.6623 Remote Similarity NPC210003
0.6556 Remote Similarity NPC14187
0.6538 Remote Similarity NPC145038
0.6538 Remote Similarity NPC56077
0.6538 Remote Similarity NPC281131
0.6538 Remote Similarity NPC253662
0.6538 Remote Similarity NPC179950
0.6538 Remote Similarity NPC158674
0.6538 Remote Similarity NPC323593
0.6538 Remote Similarity NPC88789
0.6538 Remote Similarity NPC203500
0.6538 Remote Similarity NPC491374
0.6471 Remote Similarity NPC150164
0.6452 Remote Similarity NPC25523
0.642 Remote Similarity NPC148710
0.641 Remote Similarity NPC19388
0.641 Remote Similarity NPC240431
0.641 Remote Similarity NPC55786
0.6341 Remote Similarity NPC607707
0.6329 Remote Similarity NPC234739
0.6327 Remote Similarity NPC470720
0.6277 Remote Similarity NPC480441
0.6265 Remote Similarity NPC488072
0.625 Remote Similarity NPC488080
0.625 Remote Similarity NPC169977
0.625 Remote Similarity NPC73511
0.6224 Remote Similarity NPC470717
0.6222 Remote Similarity NPC76831
0.622 Remote Similarity NPC601144
0.622 Remote Similarity NPC609478
0.6207 Remote Similarity NPC186816
0.6203 Remote Similarity NPC58053
0.618 Remote Similarity NPC72016
0.618 Remote Similarity NPC606657
0.6173 Remote Similarity NPC42773
0.6173 Remote Similarity NPC45522
0.6173 Remote Similarity NPC325555
0.6173 Remote Similarity NPC226304
0.6145 Remote Similarity NPC311830
0.6136 Remote Similarity NPC240306
0.6125 Remote Similarity NPC8573
0.6111 Remote Similarity NPC5319
0.6098 Remote Similarity NPC307938
0.6071 Remote Similarity NPC203050
0.6071 Remote Similarity NPC225434
0.6061 Remote Similarity NPC470719
0.6049 Remote Similarity NPC186807
0.6049 Remote Similarity NPC603655
0.6026 Remote Similarity NPC288084
0.6 Remote Similarity NPC143851
0.5976 Remote Similarity NPC599850
0.5926 Remote Similarity NPC197896
0.5926 Remote Similarity NPC313163
0.5921 Remote Similarity NPC191154
0.5882 Remote Similarity NPC601586
0.5862 Remote Similarity NPC480466
0.5854 Remote Similarity NPC181712
0.5844 Remote Similarity NPC134819
0.5833 Remote Similarity NPC101026
0.5833 Remote Similarity NPC488077
0.5797 Remote Similarity NPC262094
0.5789 Remote Similarity NPC121703
0.5773 Remote Similarity NPC470712
0.5761 Remote Similarity NPC486577
0.575 Remote Similarity NPC67037
0.575 Remote Similarity NPC255615
0.5747 Remote Similarity NPC480463
0.5714 Remote Similarity NPC80140
0.5682 Remote Similarity NPC139320
0.5679 Remote Similarity NPC111929
0.5679 Remote Similarity NPC320283
0.5679 Remote Similarity NPC41121
0.5663 Remote Similarity NPC27640
0.5647 Remote Similarity NPC605067
0.5625 Remote Similarity NPC34531
0.5618 Remote Similarity NPC275454
0.561 Remote Similarity NPC19709
0.561 Remote Similarity NPC238376
0.5579 Remote Similarity NPC135358
0.5568 Remote Similarity NPC8856
0.5568 Remote Similarity NPC473682
0.5556 Remote Similarity NPC153758
0.5556 Remote Similarity NPC156869
0.5542 Remote Similarity NPC168822
0.5529 Remote Similarity NPC168584
0.5529 Remote Similarity NPC219904
0.5529 Remote Similarity NPC609451
0.5517 Remote Similarity NPC170052
0.5517 Remote Similarity NPC135846
0.5506 Remote Similarity NPC29958
0.5505 Remote Similarity NPC223860
0.549 Remote Similarity NPC470713
0.5488 Remote Similarity NPC473043
0.5488 Remote Similarity NPC331652
0.5488 Remote Similarity NPC160515
0.5476 Remote Similarity NPC22195
0.5476 Remote Similarity NPC21190
0.5444 Remote Similarity NPC471748
0.5422 Remote Similarity NPC127546
0.5422 Remote Similarity NPC57625
0.5422 Remote Similarity NPC108831
0.5422 Remote Similarity NPC173637
0.5422 Remote Similarity NPC317489
0.5422 Remote Similarity NPC223424
0.5422 Remote Similarity NPC182634
0.5422 Remote Similarity NPC600591
0.5412 Remote Similarity NPC21100
0.5412 Remote Similarity NPC27942
0.5412 Remote Similarity NPC60966
0.5412 Remote Similarity NPC117260
0.5412 Remote Similarity NPC201292
0.5402 Remote Similarity NPC206123
0.5368 Remote Similarity NPC475382
0.5357 Remote Similarity NPC156457
0.5349 Remote Similarity NPC191306
0.5349 Remote Similarity NPC175107
0.5341 Remote Similarity NPC190003
0.5301 Remote Similarity NPC135599
0.5301 Remote Similarity NPC73855
0.5301 Remote Similarity NPC113968
0.5301 Remote Similarity NPC328940
0.5301 Remote Similarity NPC277174
0.5301 Remote Similarity NPC606877
0.5294 Remote Similarity NPC245014
0.5294 Remote Similarity NPC58716
0.5294 Remote Similarity NPC105025
0.5294 Remote Similarity NPC45638
0.5287 Remote Similarity NPC80188
0.5281 Remote Similarity NPC254855
0.5281 Remote Similarity NPC94610
0.5275 Remote Similarity NPC470405
0.5269 Remote Similarity NPC46202
0.5269 Remote Similarity NPC488073
0.5263 Remote Similarity NPC142142
0.5238 Remote Similarity NPC45618
0.5233 Remote Similarity NPC59534
0.5233 Remote Similarity NPC138540
0.5227 Remote Similarity NPC220169
0.5222 Remote Similarity NPC278419
0.5222 Remote Similarity NPC179198
0.5217 Remote Similarity NPC22062
0.5217 Remote Similarity NPC473634
0.5217 Remote Similarity NPC138811
0.5213 Remote Similarity NPC483414
0.52 Remote Similarity NPC48984
0.5189 Remote Similarity NPC138990
0.5176 Remote Similarity NPC93337
0.5176 Remote Similarity NPC265530
0.5176 Remote Similarity NPC146792
0.5172 Remote Similarity NPC479402
0.5165 Remote Similarity NPC603300
0.5161 Remote Similarity NPC115674

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC497931 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
0.6111 Remote Similarity NPD7804 Clinical (unspecified phase)
0.5789 Remote Similarity NPD7808 Phase 3
0.5699 Remote Similarity NPD7251 Phase 2

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