Natural Product: NPC496251

Natural Product IDNPC496251
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-6-[[(2~{R},3~{R},4~{S},5~{S},6~{S})-3,5-dihydroxy-6-methyl-4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-2-(3,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-chromen-4-one
IUPAC Name 3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-6-[[(2~{R},3~{R},4~{S},5~{S},6~{S})-3,5-dihydroxy-6-methyl-4-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-2-(3,4-dihydroxyphenyl)-5-hydroxy-7-methoxy-chromen-4-one
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:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0003531] Flavonoid-3-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 NMGVHLDIHNFGQB-ONDXUVFZSA-N
Standard InCHI InChI=1S/C34H42O20/c1-10-20(38)24(42)26(44)33(50-10)53-30-21(39)11(2)49-32(28(30)46)48-9-18-22(40)25(43)27(45)34(52-18)54-31-23(41)19-16(37)7-13(47-3)8-17(19)51-29(31)12-4-5-14(35)15(36)6-12/h4-8,10-11,18,20-22,24-28,30,32-40,42-46H,9H2,1-3H3/t10-,11+,18-,20+,21+,22-,24+,25+,26-,27-,28-,30+,32-,33+,34+/m1/s1
SMILES COC1=CC(O)=C2C(=O)C(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@H](O[C@@H]5O[C@H](C)[C@H](O)[C@H](O)[C@H]5O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)=C(C3=CC=C(O)C(O)=C3)OC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   770.23 Volume:   699.994
?
Van der Waals volume.
Dense:   1.1 LogP:   0.631
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.431
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.975
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   36.0
TPSA:   317.35
?
Topological Polar Surface Area.
 H-Bond Acceptor:   20.0
H-Bond Donor:   11.0 Rings:   6.0
Heavy Atoms:   20.0

MedChem Properties

QED Drug-Likeness Score:   0.1 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.386 Fsp3:   0.559
MCE-18:   153.34
?
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:   0.628 Fluc inhibitor:   0.327
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.827
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.593
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.144 Promiscuous compounds:   0.506

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.568 MDCK Permeability:   -5.219
Pgp-inhibitor:   0.0 Pgp-substrate:   0.542
PAMPA:   0.999
?
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):   0.946
20% Bioavailability (F20%):   0.391 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.04
Plasma Protein Binding (PPB):   78.258% Volume Distribution (VD):   -0.203
Fu: 20.083%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.557
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:   0.011
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.109
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.805
HLM stability:   0.733
?
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):  1.076 Half-life (T1/2):  4.543

ADMET: Toxicity

hERG Blockers:  0.01 hERG Blockers (10um):  0.099
Human Hepatotoxicity (H-HT):  0.398 Drug-induced Liver Injury (DILI):  0.988
AMES Toxicity:  0.983 Rat Oral Acute Toxicity:  0.009
Maximum Recommended Daily Dose:  0.014 Skin Sensitization:  1.0
Carcinogencity:  0.024 Eye Corrosion:  0.0
Eye Irritation:  0.067 Respiratory Toxicity:  0.006
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.991
Hematotoxicity:  0.197 Drug-induced Nephrotoxicity:  0.338
Genotoxicity:  0.755 RPMI-8226 Immunitoxicity:  0.148
A549 Cytotoxicity:  0.98 Hek293 Cytotoxicity:  0.7
BCF:   0.441
?
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:   3.174
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.715
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.927
?
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
NPO20596 Rhamnus petiolaris Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO25962 Rhamnus cathartica Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20596 Rhamnus petiolaris Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11963 Rhamnus disperma Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25962 Rhamnus cathartica Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25962 Rhamnus cathartica Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25962 Rhamnus cathartica Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11963 Rhamnus disperma Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20596 Rhamnus petiolaris Species Rhamnaceae 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 NPC496251 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
0.7576 Intermediate Similarity NPC292019
0.7576 Intermediate Similarity NPC202908
0.7527 Intermediate Similarity NPC186816
0.7471 Intermediate Similarity NPC271692
0.7368 Intermediate Similarity NPC470443
0.7083 Intermediate Similarity NPC126784
0.7083 Intermediate Similarity NPC241423
0.7053 Intermediate Similarity NPC203259
0.7053 Intermediate Similarity NPC33054
0.7053 Intermediate Similarity NPC176740
0.7053 Intermediate Similarity NPC471725
0.7053 Intermediate Similarity NPC134532
0.7053 Intermediate Similarity NPC602582
0.699 Remote Similarity NPC480441
0.6961 Remote Similarity NPC189564
0.6947 Remote Similarity NPC67105
0.6875 Remote Similarity NPC210073
0.68 Remote Similarity NPC473073
0.6703 Remote Similarity NPC46420
0.67 Remote Similarity NPC142142
0.6596 Remote Similarity NPC605784
0.6593 Remote Similarity NPC158674
0.6535 Remote Similarity NPC486577
0.6442 Remote Similarity NPC14187
0.6436 Remote Similarity NPC606657
0.6429 Remote Similarity NPC173582
0.6429 Remote Similarity NPC265885
0.6429 Remote Similarity NPC181465
0.6429 Remote Similarity NPC215710
0.6429 Remote Similarity NPC473438
0.6429 Remote Similarity NPC253788
0.6408 Remote Similarity NPC101636
0.6355 Remote Similarity NPC25523
0.6311 Remote Similarity NPC476472
0.6311 Remote Similarity NPC294815
0.6311 Remote Similarity NPC16194
0.6304 Remote Similarity NPC249281
0.63 Remote Similarity NPC473571
0.63 Remote Similarity NPC110941
0.6275 Remote Similarity NPC483416
0.6275 Remote Similarity NPC473327
0.6263 Remote Similarity NPC44931
0.6263 Remote Similarity NPC67326
0.6263 Remote Similarity NPC39834
0.6263 Remote Similarity NPC227508
0.6238 Remote Similarity NPC488073
0.6238 Remote Similarity NPC488074
0.6237 Remote Similarity NPC136042
0.6226 Remote Similarity NPC203145
0.6211 Remote Similarity NPC611303
0.62 Remote Similarity NPC22062
0.62 Remote Similarity NPC65563
0.62 Remote Similarity NPC473634
0.62 Remote Similarity NPC470949
0.62 Remote Similarity NPC138811
0.62 Remote Similarity NPC156869
0.619 Remote Similarity NPC470446
0.6186 Remote Similarity NPC276377
0.617 Remote Similarity NPC84362
0.617 Remote Similarity NPC27640
0.6117 Remote Similarity NPC209296
0.5962 Remote Similarity NPC122467
0.596 Remote Similarity NPC116864
0.596 Remote Similarity NPC244776
0.5943 Remote Similarity NPC470445
0.5938 Remote Similarity NPC59534
0.5926 Remote Similarity NPC121703
0.5922 Remote Similarity NPC240306
0.5918 Remote Similarity NPC116458
0.5918 Remote Similarity NPC246943
0.5882 Remote Similarity NPC150164
0.5865 Remote Similarity NPC483415
0.5833 Remote Similarity NPC305811
0.581 Remote Similarity NPC32641
0.581 Remote Similarity NPC256188
0.58 Remote Similarity NPC265115
0.5789 Remote Similarity NPC127546
0.5789 Remote Similarity NPC57625
0.5789 Remote Similarity NPC173637
0.5789 Remote Similarity NPC317489
0.5789 Remote Similarity NPC238376
0.5789 Remote Similarity NPC223424
0.5789 Remote Similarity NPC600591
0.5776 Remote Similarity NPC241781
0.5727 Remote Similarity NPC470451
0.5714 Remote Similarity NPC65711
0.5701 Remote Similarity NPC89127
0.5686 Remote Similarity NPC471079
0.566 Remote Similarity NPC72016
0.566 Remote Similarity NPC35119
0.5641 Remote Similarity NPC209550
0.5625 Remote Similarity NPC19709
0.5588 Remote Similarity NPC251417
0.5577 Remote Similarity NPC605592
0.5567 Remote Similarity NPC297987
0.5566 Remote Similarity NPC245452
0.5566 Remote Similarity NPC483414
0.5565 Remote Similarity NPC488086
0.5565 Remote Similarity NPC249560
0.5556 Remote Similarity NPC471669
0.5556 Remote Similarity NPC483413
0.5534 Remote Similarity NPC480466
0.5505 Remote Similarity NPC470449
0.5481 Remote Similarity NPC275454
0.5463 Remote Similarity NPC488089
0.5455 Remote Similarity NPC135358
0.5439 Remote Similarity NPC277532
0.5429 Remote Similarity NPC293626
0.5429 Remote Similarity NPC303913
0.5421 Remote Similarity NPC12013
0.5421 Remote Similarity NPC11432
0.5421 Remote Similarity NPC477613
0.5405 Remote Similarity NPC470455
0.54 Remote Similarity NPC488071
0.5378 Remote Similarity NPC138990
0.5377 Remote Similarity NPC204693
0.537 Remote Similarity NPC229409
0.5364 Remote Similarity NPC298171
0.5357 Remote Similarity NPC89052
0.5354 Remote Similarity NPC52550
0.5351 Remote Similarity NPC303694
0.534 Remote Similarity NPC95866
0.5333 Remote Similarity NPC175429
0.5327 Remote Similarity NPC153755
0.5306 Remote Similarity NPC289667
0.5273 Remote Similarity NPC470447
0.5248 Remote Similarity NPC175107
0.5229 Remote Similarity NPC37668
0.5229 Remote Similarity NPC473623
0.5221 Remote Similarity NPC11468
0.5204 Remote Similarity NPC111929
0.5204 Remote Similarity NPC320283
0.5204 Remote Similarity NPC41121
0.52 Remote Similarity NPC349108
0.5185 Remote Similarity NPC475366
0.5179 Remote Similarity NPC223426
0.5179 Remote Similarity NPC602448
0.5172 Remote Similarity NPC188871
0.5152 Remote Similarity NPC108831
0.5152 Remote Similarity NPC182634
0.5149 Remote Similarity NPC42773
0.5149 Remote Similarity NPC45522
0.5149 Remote Similarity NPC599850
0.5146 Remote Similarity NPC223747
0.5143 Remote Similarity NPC254540
0.514 Remote Similarity NPC155877
0.5135 Remote Similarity NPC483412
0.5133 Remote Similarity NPC81042
0.513 Remote Similarity NPC173837
0.5113 Remote Similarity NPC33083
0.51 Remote Similarity NPC145038
0.51 Remote Similarity NPC56077
0.51 Remote Similarity NPC281131
0.51 Remote Similarity NPC253662
0.51 Remote Similarity NPC179950
0.51 Remote Similarity NPC277205
0.51 Remote Similarity NPC37919
0.51 Remote Similarity NPC88789
0.51 Remote Similarity NPC491374
0.5098 Remote Similarity NPC219904
0.5096 Remote Similarity NPC190003
0.5096 Remote Similarity NPC355481
0.5094 Remote Similarity NPC187379
0.5094 Remote Similarity NPC609888
0.5093 Remote Similarity NPC115674
0.5089 Remote Similarity NPC221342
0.5089 Remote Similarity NPC476470
0.5083 Remote Similarity NPC156785
0.5083 Remote Similarity NPC162394
0.5051 Remote Similarity NPC473043
0.5051 Remote Similarity NPC135599
0.5051 Remote Similarity NPC73855
0.5051 Remote Similarity NPC331652
0.5051 Remote Similarity NPC113968
0.5051 Remote Similarity NPC328940
0.5051 Remote Similarity NPC277174
0.5051 Remote Similarity NPC606877
0.5047 Remote Similarity NPC471748
0.5046 Remote Similarity NPC64425
0.5041 Remote Similarity NPC480444
0.5041 Remote Similarity NPC488078
0.5038 Remote Similarity NPC482520
0.5038 Remote Similarity NPC482519

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC496251 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
0.7872 Intermediate Similarity NPD7251 Phase 2
0.7053 Intermediate Similarity NPD6797 Phase 2
0.6699 Remote Similarity NPD7808 Phase 3
0.6117 Remote Similarity NPD7054 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