Natural Product: NPC528441

Natural Product IDNPC528441
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[4-(hydroxymethyl)phenoxy]tetrahydropyran-3,4,5-triol
IUPAC Name (2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[4-(hydroxymethyl)phenoxy]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 PUQSUZTXKPLAPR-KSSYENDESA-N
Standard InCHI InChI=1S/C13H18O7/c14-5-7-1-3-8(4-2-7)19-13-12(18)11(17)10(16)9(6-15)20-13/h1-4,9-18H,5-6H2/t9-,10+,11+,12-,13-/m1/s1
SMILES OCC1=CC=C(O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)C=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.11 Volume:   269.914
?
Van der Waals volume.
Dense:   1.06 LogP:   -0.557
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.004
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.996
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   119.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.45 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.321 Fsp3:   0.538
MCE-18:   45.5
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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:   0.416 Fluc inhibitor:   0.012
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.032
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.008
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.393 Promiscuous compounds:   0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.18 MDCK Permeability:   -4.982
Pgp-inhibitor:   0.0 Pgp-substrate:   0.058
PAMPA:   0.913
?
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):   0.991
20% Bioavailability (F20%):   0.85 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.87

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.092 MRP1:   0.283
Plasma Protein Binding (PPB):   55.025% Volume Distribution (VD):   -0.066
Fu: 43.044%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.952
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.004
BSEP inhibitor:   0.001

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:   0.0
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.248
HLM stability:   0.008
?
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):  3.968 Half-life (T1/2):  2.069

ADMET: Toxicity

hERG Blockers:  0.024 hERG Blockers (10um):  0.101
Human Hepatotoxicity (H-HT):  0.698 Drug-induced Liver Injury (DILI):  0.721
AMES Toxicity:  0.941 Rat Oral Acute Toxicity:  0.026
Maximum Recommended Daily Dose:  0.015 Skin Sensitization:  0.995
Carcinogencity:  0.488 Eye Corrosion:  0.001
Eye Irritation:  0.747 Respiratory Toxicity:  0.097
Drug-induced Neurotoxicity:  0.152 Ototoxicity:  0.852
Hematotoxicity:  0.601 Drug-induced Nephrotoxicity:  0.775
Genotoxicity:  0.599 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.402 Hek293 Cytotoxicity:  0.216
BCF:   0.329
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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:   2.313
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.805
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.908
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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
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. tuber n.a. PMID[15180301]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[17381154]
NPO12933 Gymnadenia conopsea Species Orchidaceae Eukaryota tubers n.a. n.a. PMID[18348533]
NPO12933 Gymnadenia conopsea Species Orchidaceae Eukaryota n.a. tuber n.a. PMID[21322946]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[25843525]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12933 Gymnadenia conopsea Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58789 Citrullus colocynthis (L.) Genus Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61410 Anoectochilus formosanus Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12933 Gymnadenia conopsea Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12933 Gymnadenia conopsea Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22309 Gastrodia elata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12933 Gymnadenia conopsea Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22309 Gastrodia elata Species Orchidaceae 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 NPC528441 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 NPC269242
0.7857 Intermediate Similarity NPC212729
0.7857 Intermediate Similarity NPC604498
0.75 Intermediate Similarity NPC294470
0.7174 Intermediate Similarity NPC60589
0.7174 Intermediate Similarity NPC469708
0.7174 Intermediate Similarity NPC609376
0.7083 Intermediate Similarity NPC166040
0.7021 Intermediate Similarity NPC200092
0.6875 Remote Similarity NPC80098
0.6667 Remote Similarity NPC142319
0.6667 Remote Similarity NPC226712
0.6512 Remote Similarity NPC228907
0.6458 Remote Similarity NPC299144
0.6346 Remote Similarity NPC251102
0.6346 Remote Similarity NPC210298
0.6346 Remote Similarity NPC604356
0.6226 Remote Similarity NPC26080
0.6226 Remote Similarity NPC165686
0.6154 Remote Similarity NPC218685
0.6122 Remote Similarity NPC604439
0.6078 Remote Similarity NPC166168
0.6042 Remote Similarity NPC153149
0.6038 Remote Similarity NPC479028
0.6038 Remote Similarity NPC479031
0.6 Remote Similarity NPC608788
0.5962 Remote Similarity NPC40377
0.5957 Remote Similarity NPC276195
0.5918 Remote Similarity NPC25817
0.5833 Remote Similarity NPC217854
0.5769 Remote Similarity NPC214454
0.5738 Remote Similarity NPC605700
0.5714 Remote Similarity NPC192810
0.5686 Remote Similarity NPC12308
0.566 Remote Similarity NPC310661
0.566 Remote Similarity NPC9912
0.56 Remote Similarity NPC9248
0.5593 Remote Similarity NPC610808
0.5577 Remote Similarity NPC221090
0.551 Remote Similarity NPC484157
0.5455 Remote Similarity NPC472024
0.5455 Remote Similarity NPC270849
0.5455 Remote Similarity NPC205054
0.5455 Remote Similarity NPC23084
0.5455 Remote Similarity NPC19470
0.5455 Remote Similarity NPC606892
0.5439 Remote Similarity NPC222455
0.5424 Remote Similarity NPC294166
0.5424 Remote Similarity NPC115022
0.541 Remote Similarity NPC248119
0.541 Remote Similarity NPC175275
0.5357 Remote Similarity NPC26653
0.5357 Remote Similarity NPC214910
0.5357 Remote Similarity NPC80600
0.5357 Remote Similarity NPC164599
0.5357 Remote Similarity NPC481303
0.5333 Remote Similarity NPC479030
0.5333 Remote Similarity NPC8497
0.5323 Remote Similarity NPC264381
0.5323 Remote Similarity NPC259767
0.5323 Remote Similarity NPC295970
0.5312 Remote Similarity NPC212099
0.5294 Remote Similarity NPC152722
0.5283 Remote Similarity NPC69513
0.5283 Remote Similarity NPC145900
0.5263 Remote Similarity NPC248355
0.5263 Remote Similarity NPC479029
0.5254 Remote Similarity NPC146540
0.5238 Remote Similarity NPC471029
0.5238 Remote Similarity NPC601944
0.5192 Remote Similarity NPC198798
0.5185 Remote Similarity NPC48863
0.5185 Remote Similarity NPC251981
0.5185 Remote Similarity NPC13745
0.5179 Remote Similarity NPC485268
0.5179 Remote Similarity NPC83975
0.5172 Remote Similarity NPC55040
0.5161 Remote Similarity NPC210192
0.5156 Remote Similarity NPC101116
0.5156 Remote Similarity NPC186406
0.5156 Remote Similarity NPC108674
0.5152 Remote Similarity NPC116922
0.5094 Remote Similarity NPC36434
0.5091 Remote Similarity NPC215833
0.5088 Remote Similarity NPC210015
0.5088 Remote Similarity NPC210478
0.5085 Remote Similarity NPC302378
0.5085 Remote Similarity NPC59324
0.5085 Remote Similarity NPC85799
0.5085 Remote Similarity NPC303422
0.5085 Remote Similarity NPC218003
0.5085 Remote Similarity NPC34456
0.5082 Remote Similarity NPC37468
0.5082 Remote Similarity NPC186418
0.5082 Remote Similarity NPC479374
0.5079 Remote Similarity NPC57587
0.5077 Remote Similarity NPC185103
0.5077 Remote Similarity NPC170475
0.5077 Remote Similarity NPC606202

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC528441 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
0.6667 Remote Similarity NPD1091 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