Natural Product: NPC497665

Natural Product IDNPC497665
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{S},3~{R},4~{R},5~{R},6~{S})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-4,5-dihydroxy-2-(hydroxymethyl)-6-[(1~{S},2~{S},4~{S},5'~{S},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5'-(hydroxymethyl)-7,9,13-trimethyl-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-tetrahydropyran]-16-yl]oxy-tetrahydropyran-3-yl]oxy-6-methyl-tetrahydropyran-3,4,5-triol
IUPAC Name (2~{S},3~{R},4~{R},5~{R},6~{S})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-4,5-dihydroxy-2-(hydroxymethyl)-6-[(1~{S},2~{S},4~{S},5'~{S},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5'-(hydroxymethyl)-7,9,13-trimethyl-spiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-tetrahydropyran]-16-yl]oxy-tetrahydropyran-3-yl]oxy-6-methyl-tetrahydropyran-3,4,5-triol
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 JJQPAMVBVCTWHX-UJVHZNLISA-N
Standard InCHI InChI=1S/C39H62O13/c1-18-28-26(52-39(18)12-7-20(15-40)17-47-39)14-25-23-6-5-21-13-22(8-10-37(21,3)24(23)9-11-38(25,28)4)49-36-33(46)31(44)34(27(16-41)50-36)51-35-32(45)30(43)29(42)19(2)48-35/h5,18-20,22-36,40-46H,6-17H2,1-4H3/t18-,19-,20-,22-,23+,24-,25-,26-,27+,28-,29-,30+,31+,32+,33+,34+,35-,36+,37-,38-,39+/m0/s1
SMILES C[C@@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O[C@H]3CC[C@@]4(C)C(=CC[C@H]5[C@@H]6C[C@@H]7O[C@]8(CC[C@@H](CO)CO8)[C@@H](C)[C@@H]7[C@@]6(C)CC[C@@H]54)C3)O[C@@H]2CO)[C@H](O)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   738.42 Volume:   726.285
?
Van der Waals volume.
Dense:   1.017 LogP:   2.201
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.67
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.094
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   42.0
TPSA:   196.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   7.0 Rings:   8.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.193 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.277 Fsp3:   0.949
MCE-18:   198.421
?
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:   0.754 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.185 Promiscuous compounds:   0.01

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.62 MDCK Permeability:   -4.941
Pgp-inhibitor:   0.0 Pgp-substrate:   0.907
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):   0.002
20% Bioavailability (F20%):   0.077 30% Bioavailability (F30%):   0.714
50% Bioavailability (F50%):   0.888

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.04
Plasma Protein Binding (PPB):   68.017% Volume Distribution (VD):   -0.423
Fu: 27.603%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.133
BSEP inhibitor:   0.045

ADMET: Metabolism

CYP1A2-inhibitor:   0.039 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:   0.001
CYP3A4-inhibitor:   0.675 CYP3A4-substrate:   0.168
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.007
?
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):  1.196 Half-life (T1/2):  2.696

ADMET: Toxicity

hERG Blockers:  0.006 hERG Blockers (10um):  0.025
Human Hepatotoxicity (H-HT):  0.647 Drug-induced Liver Injury (DILI):  0.976
AMES Toxicity:  0.968 Rat Oral Acute Toxicity:  0.029
Maximum Recommended Daily Dose:  0.021 Skin Sensitization:  1.0
Carcinogencity:  0.685 Eye Corrosion:  0.0
Eye Irritation:  0.004 Respiratory Toxicity:  0.003
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.992
Hematotoxicity:  0.418 Drug-induced Nephrotoxicity:  0.995
Genotoxicity:  0.209 RPMI-8226 Immunitoxicity:  0.328
A549 Cytotoxicity:  0.943 Hek293 Cytotoxicity:  0.803
BCF:   1.645
?
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:   3.446
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.6
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.985
?
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
NPO17650 Dioscorea septemloba Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17650 Dioscorea septemloba Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17650 Dioscorea septemloba Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17650 Dioscorea septemloba Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17650 Dioscorea septemloba Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17650 Dioscorea septemloba Species Dioscoreaceae 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 NPC497665 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
0.9186 High Similarity NPC470432
0.9186 High Similarity NPC230507
0.8495 Intermediate Similarity NPC6806
0.8387 Intermediate Similarity NPC248746
0.7959 Intermediate Similarity NPC475550
0.7708 Intermediate Similarity NPC470433
0.7708 Intermediate Similarity NPC46190
0.7708 Intermediate Similarity NPC171073
0.7629 Intermediate Similarity NPC477809
0.76 Intermediate Similarity NPC269297
0.76 Intermediate Similarity NPC222202
0.7528 Intermediate Similarity NPC181845
0.7475 Intermediate Similarity NPC480555
0.7475 Intermediate Similarity NPC150372
0.7396 Intermediate Similarity NPC14704
0.7347 Intermediate Similarity NPC602423
0.7216 Intermediate Similarity NPC113044
0.7216 Intermediate Similarity NPC283829
0.7216 Intermediate Similarity NPC161676
0.72 Intermediate Similarity NPC42171
0.72 Intermediate Similarity NPC300557
0.7184 Intermediate Similarity NPC475333
0.7184 Intermediate Similarity NPC224098
0.7184 Intermediate Similarity NPC208383
0.7075 Intermediate Similarity NPC477811
0.7048 Intermediate Similarity NPC480554
0.6916 Remote Similarity NPC480553
0.6847 Remote Similarity NPC224314
0.6699 Remote Similarity NPC249553
0.6698 Remote Similarity NPC32361
0.6667 Remote Similarity NPC15249
0.6667 Remote Similarity NPC25455
0.6636 Remote Similarity NPC194207
0.6636 Remote Similarity NPC22779
0.6607 Remote Similarity NPC480556
0.6526 Remote Similarity NPC325828
0.6389 Remote Similarity NPC309278
0.6383 Remote Similarity NPC486114
0.6339 Remote Similarity NPC232054
0.6214 Remote Similarity NPC305423
0.618 Remote Similarity NPC486119
0.6162 Remote Similarity NPC250393
0.6106 Remote Similarity NPC31896
0.61 Remote Similarity NPC121453
0.6075 Remote Similarity NPC182900
0.5932 Remote Similarity NPC477808
0.5922 Remote Similarity NPC107962
0.5882 Remote Similarity NPC19400
0.5816 Remote Similarity NPC485594
0.581 Remote Similarity NPC141433
0.5804 Remote Similarity NPC13193
0.5794 Remote Similarity NPC161738
0.575 Remote Similarity NPC210569
0.5728 Remote Similarity NPC306131
0.5728 Remote Similarity NPC200802
0.5714 Remote Similarity NPC94272
0.5714 Remote Similarity NPC485595
0.5714 Remote Similarity NPC6295
0.5714 Remote Similarity NPC477807
0.5688 Remote Similarity NPC122819
0.5652 Remote Similarity NPC100451
0.5636 Remote Similarity NPC124677
0.562 Remote Similarity NPC15918
0.561 Remote Similarity NPC305771
0.561 Remote Similarity NPC94072
0.561 Remote Similarity NPC169816
0.5577 Remote Similarity NPC107188
0.5575 Remote Similarity NPC247037
0.5536 Remote Similarity NPC97700
0.5536 Remote Similarity NPC73243
0.5536 Remote Similarity NPC244086
0.5536 Remote Similarity NPC184617
0.5536 Remote Similarity NPC84956
0.5536 Remote Similarity NPC30856
0.5517 Remote Similarity NPC23808
0.5517 Remote Similarity NPC87998
0.5446 Remote Similarity NPC475182
0.5437 Remote Similarity NPC477451
0.5435 Remote Similarity NPC235126
0.5435 Remote Similarity NPC242419
0.537 Remote Similarity NPC70204
0.5364 Remote Similarity NPC42482
0.536 Remote Similarity NPC244431
0.531 Remote Similarity NPC150057
0.531 Remote Similarity NPC147753
0.5299 Remote Similarity NPC249265
0.5294 Remote Similarity NPC308140
0.5294 Remote Similarity NPC287885
0.5263 Remote Similarity NPC294129
0.5263 Remote Similarity NPC102016
0.5263 Remote Similarity NPC95051
0.5254 Remote Similarity NPC83137
0.5238 Remote Similarity NPC263359
0.5229 Remote Similarity NPC195297
0.5225 Remote Similarity NPC98696
0.5225 Remote Similarity NPC40440
0.5214 Remote Similarity NPC232037
0.521 Remote Similarity NPC132080
0.5204 Remote Similarity NPC144790
0.5204 Remote Similarity NPC149400
0.5196 Remote Similarity NPC165439
0.5192 Remote Similarity NPC234352
0.5189 Remote Similarity NPC206003
0.5189 Remote Similarity NPC473610
0.5133 Remote Similarity NPC92890
0.5128 Remote Similarity NPC475625
0.5096 Remote Similarity NPC297348
0.5096 Remote Similarity NPC249204
0.5096 Remote Similarity NPC48339
0.5096 Remote Similarity NPC141769
0.5096 Remote Similarity NPC477547
0.5091 Remote Similarity NPC475670
0.5046 Remote Similarity NPC295980
0.5044 Remote Similarity NPC265275
0.5042 Remote Similarity NPC218571
0.5042 Remote Similarity NPC487615

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC497665 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
0.6526 Remote Similarity NPD8171 Phase 2
0.5865 Remote Similarity NPD8170 Phase 2
0.5688 Remote Similarity NPD8449 Approved
0.531 Remote Similarity NPD8450 Suspended

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