Natural Product: NPC85753

Natural Product IDNPC85753
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ALIOKRACUZLOCC-RBUKOAKNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 100956085
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones
            • [CHEMONTID:0001362] Flavanonols

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 ALIOKRACUZLOCC-RBUKOAKNSA-N
Standard InCHI InChI=1S/C19H18O8/c1-8(20)2-4-10-12(22)7-14-15(16(10)24)17(25)18(26)19(27-14)9-3-5-11(21)13(23)6-9/h3,5-7,18-19,21-24,26H,2,4H2,1H3/t18-,19+/m0/s1
SMILES CC(=O)CCc1c(cc2c(c1O)C(=O)[C@@H]([C@@H](c1ccc(c(c1)O)O)O2)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   360.741
?
Van der Waals volume.
Dense:   1.037 LogP:   0.992
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.339
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.261
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   144.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.509 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.577 Fsp3:   0.263
MCE-18:   66.5
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.619 Fluc inhibitor:   0.254
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.694
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.246
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.147 Promiscuous compounds:   0.129

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.987 MDCK Permeability:   -4.889
Pgp-inhibitor:   0.186 Pgp-substrate:   0.009
PAMPA:   0.839
?
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):   0.135
20% Bioavailability (F20%):   0.182 30% Bioavailability (F30%):   0.965
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.757
Plasma Protein Binding (PPB):   97.431% Volume Distribution (VD):   -0.412
Fu: 2.292%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.114
BSEP inhibitor:   0.238

ADMET: Metabolism

CYP1A2-inhibitor:   0.885 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.393 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.733 CYP2D6-substrate:   0.971
CYP3A4-inhibitor:   0.069 CYP3A4-substrate:   0.109
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.596
HLM stability:   0.861
?
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):  10.115 Half-life (T1/2):  1.816

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.475
Human Hepatotoxicity (H-HT):  0.868 Drug-induced Liver Injury (DILI):  0.402
AMES Toxicity:  0.436 Rat Oral Acute Toxicity:  0.373
Maximum Recommended Daily Dose:  0.443 Skin Sensitization:  1.0
Carcinogencity:  0.202 Eye Corrosion:  0.007
Eye Irritation:  0.986 Respiratory Toxicity:  0.573
Drug-induced Neurotoxicity:  0.079 Ototoxicity:  0.729
Hematotoxicity:  0.324 Drug-induced Nephrotoxicity:  0.729
Genotoxicity:  0.818 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.767 Hek293 Cytotoxicity:  0.32
BCF:   0.611
?
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:   3.205
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.51
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.993
?
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
NPO809 Leitneria floridana Species Simaroubaceae Eukaryota n.a. aerial part n.a. PMID[11141127]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. leaf n.a. PMID[15595606]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16562827]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota roots Phitsanulok Province, Thailand 2004-MAY PMID[17480099]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. root n.a. PMID[17480099]
NPO4382 Elmerrillia papuana n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3357 Alnus cordata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4628 Aloe deltoideodonta Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2455 Thermopsis mollis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1490 Goldfussia yunnanensis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8807 Laurentia longiflora n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO809 Leitneria floridana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9608 Lepraria citrina Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8977 Notholaena aschenborniana Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9881 Petrosia hebes Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6828 Purpura aperta Species Muricidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25475 Syphonota geographica Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27517 Crinum latifolium Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5635 Bauhinia purpurea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25475 Syphonota geographica Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4382 Elmerrillia papuana n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO8807 Laurentia longiflora n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO809 Leitneria floridana Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9608 Lepraria citrina Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6828 Purpura aperta Species Muricidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2455 Thermopsis mollis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3357 Alnus cordata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8977 Notholaena aschenborniana Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4628 Aloe deltoideodonta Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9881 Petrosia hebes Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1490 Goldfussia yunnanensis n.a. n.a. n.a. 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 NPC85753 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
0.7069 Intermediate Similarity NPC611035
0.6912 Remote Similarity NPC22192
0.6333 Remote Similarity NPC36835
0.6333 Remote Similarity NPC246162
0.6333 Remote Similarity NPC9743
0.6333 Remote Similarity NPC260491
0.6333 Remote Similarity NPC61506
0.6333 Remote Similarity NPC240476
0.5833 Remote Similarity NPC262039
0.5738 Remote Similarity NPC246328
0.5738 Remote Similarity NPC27532
0.5526 Remote Similarity NPC282009
0.5467 Remote Similarity NPC488551
0.5385 Remote Similarity NPC287328
0.5316 Remote Similarity NPC471499
0.5263 Remote Similarity NPC470326
0.5224 Remote Similarity NPC20907
0.5132 Remote Similarity NPC186847
0.5079 Remote Similarity NPC62290
0.5079 Remote Similarity NPC142731
0.5079 Remote Similarity NPC326506
0.5079 Remote Similarity NPC600246

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC85753 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
NPD

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