Natural Product: NPC270964

Natural Product IDNPC270964
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UDAHPMHAXHYMTM-AWEZNQCLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 134138783
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones

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 UDAHPMHAXHYMTM-AWEZNQCLSA-N
Standard InCHI InChI=1S/C16H12O5/c17-8-10-11(18)6-12(19)15-13(20)7-14(21-16(10)15)9-4-2-1-3-5-9/h1-6,8,14,18-19H,7H2/t14-/m0/s1
SMILES c1ccc(cc1)[C@@H]1CC(=O)c2c(cc(c(C=O)c2O1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.07 Volume:   282.482
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Van der Waals volume.
Dense:   1.006 LogP:   3.314
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.266
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.828 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.053 Fsp3:   0.125
MCE-18:   54.778
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.766 Fluc inhibitor:   0.539
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.43
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.484
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.494 Promiscuous compounds:   0.076

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.985 MDCK Permeability:   -4.77
Pgp-inhibitor:   0.971 Pgp-substrate:   0.01
PAMPA:   0.095
?
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):   0.001
20% Bioavailability (F20%):   0.013 30% Bioavailability (F30%):   0.626
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.32 MRP1:   0.841
Plasma Protein Binding (PPB):   97.258% Volume Distribution (VD):   0.023
Fu: 2.158%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.561
OATP1B3 inhibitor:   0.939 BCRP inhibitor:   0.935
BSEP inhibitor:   0.974

ADMET: Metabolism

CYP1A2-inhibitor:   0.274 CYP1A2-substrate:   0.986
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.469 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.675
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.936
HLM stability:   0.27
?
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):  4.625 Half-life (T1/2):  1.225

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.462
Human Hepatotoxicity (H-HT):  0.771 Drug-induced Liver Injury (DILI):  0.564
AMES Toxicity:  0.625 Rat Oral Acute Toxicity:  0.757
Maximum Recommended Daily Dose:  0.692 Skin Sensitization:  0.945
Carcinogencity:  0.2 Eye Corrosion:  0.227
Eye Irritation:  0.995 Respiratory Toxicity:  0.902
Drug-induced Neurotoxicity:  0.776 Ototoxicity:  0.303
Hematotoxicity:  0.152 Drug-induced Nephrotoxicity:  0.646
Genotoxicity:  0.972 RPMI-8226 Immunitoxicity:  0.12
A549 Cytotoxicity:  0.695 Hek293 Cytotoxicity:  0.419
BCF:   1.4
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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:   4.375
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.524
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.112
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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
NPO40842 Eugenia rigida Species n.a. n.a. n.a. n.a. n.a. PMID[23547843]
NPO40842 Eugenia rigida Species n.a. n.a. n.a. n.a. n.a. PMID[27618204]
NPO40842 Eugenia rigida Species n.a. n.a. 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 7400.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MIC = 35200.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 29900.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 44400.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MIC = 70400.0 nM PMID[27618204]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[27618204]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MFC = 70.4 uM PMID[27618204]

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 NPC270964 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 NPC482121
0.8 Intermediate Similarity NPC213322
0.6667 Remote Similarity NPC76372
0.6667 Remote Similarity NPC37496
0.6538 Remote Similarity NPC271590
0.6471 Remote Similarity NPC194432
0.6471 Remote Similarity NPC215885
0.6471 Remote Similarity NPC110776
0.64 Remote Similarity NPC243083
0.64 Remote Similarity NPC13768
0.64 Remote Similarity NPC287246
0.64 Remote Similarity NPC603284
0.6226 Remote Similarity NPC2416
0.6154 Remote Similarity NPC482119
0.6154 Remote Similarity NPC482120
0.6078 Remote Similarity NPC248372
0.5962 Remote Similarity NPC4743
0.5849 Remote Similarity NPC110038
0.5741 Remote Similarity NPC476153
0.569 Remote Similarity NPC109183
0.566 Remote Similarity NPC150648
0.566 Remote Similarity NPC312391
0.566 Remote Similarity NPC37392
0.566 Remote Similarity NPC177354
0.5593 Remote Similarity NPC175504
0.5517 Remote Similarity NPC480991
0.55 Remote Similarity NPC176229
0.5472 Remote Similarity NPC204515
0.5472 Remote Similarity NPC482487
0.5424 Remote Similarity NPC107572
0.5424 Remote Similarity NPC32739
0.5333 Remote Similarity NPC122894
0.5333 Remote Similarity NPC148757
0.5333 Remote Similarity NPC3642
0.5294 Remote Similarity NPC605489
0.5294 Remote Similarity NPC606578
0.5294 Remote Similarity NPC609921
0.5283 Remote Similarity NPC22467
0.5273 Remote Similarity NPC255106
0.5273 Remote Similarity NPC235165
0.5185 Remote Similarity NPC32441
0.5185 Remote Similarity NPC79943
0.5167 Remote Similarity NPC306829
0.5152 Remote Similarity NPC132345
0.5094 Remote Similarity NPC265871
0.5094 Remote Similarity NPC205093
0.5091 Remote Similarity NPC20354
0.5082 Remote Similarity NPC250214
0.5075 Remote Similarity NPC78324
0.5075 Remote Similarity NPC115601
0.5075 Remote Similarity NPC39154
0.5075 Remote Similarity NPC208011

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC270964 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
0.64 Remote Similarity NPD1550 Phase 2
0.5185 Remote Similarity NPD1552 Clinical (unspecified phase)

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