Natural Product: NPC480991

Natural Product IDNPC480991
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XHAKQEHZYZWRLL-KRWDZBQOSA-N
IUPAC Name n.a.
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:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated 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 XHAKQEHZYZWRLL-KRWDZBQOSA-N
Standard InCHI InChI=1S/C20H22O6/c1-20(2,25)8-7-13-14(22)9-15(23)18-16(24)10-17(26-19(13)18)11-3-5-12(21)6-4-11/h3-6,9,17,21-23,25H,7-8,10H2,1-2H3/t17-/m0/s1
SMILES CC(C)(CCc1c(cc(c2C(=O)C[C@@H](c3ccc(cc3)O)Oc12)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.14 Volume:   363.093
?
Van der Waals volume.
Dense:   0.986 LogP:   2.594
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.676
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.915
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.668 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.249 Fsp3:   0.35
MCE-18:   66.111
?
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:   0.598 Fluc inhibitor:   0.77
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.498
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.36
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.124 Promiscuous compounds:   0.167

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.15 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.296 Pgp-substrate:   0.486
PAMPA:   0.104
?
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):   0.0
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.383
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.932
Plasma Protein Binding (PPB):   94.325% Volume Distribution (VD):   0.094
Fu: 7.369%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.408
OATP1B3 inhibitor:   0.918 BCRP inhibitor:   0.988
BSEP inhibitor:   0.971

ADMET: Metabolism

CYP1A2-inhibitor:   0.115 CYP1A2-substrate:   0.575
CYP2C19-inhibitor:   0.014 CYP2C19-substrate:   0.32
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.193 CYP2D6-substrate:   0.161
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.887
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.107
?
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):  5.776 Half-life (T1/2):  1.36

ADMET: Toxicity

hERG Blockers:  0.082 hERG Blockers (10um):  0.459
Human Hepatotoxicity (H-HT):  0.85 Drug-induced Liver Injury (DILI):  0.203
AMES Toxicity:  0.709 Rat Oral Acute Toxicity:  0.529
Maximum Recommended Daily Dose:  0.82 Skin Sensitization:  0.97
Carcinogencity:  0.432 Eye Corrosion:  0.004
Eye Irritation:  0.973 Respiratory Toxicity:  0.899
Drug-induced Neurotoxicity:  0.364 Ototoxicity:  0.669
Hematotoxicity:  0.156 Drug-induced Nephrotoxicity:  0.747
Genotoxicity:  0.943 RPMI-8226 Immunitoxicity:  0.159
A549 Cytotoxicity:  0.566 Hek293 Cytotoxicity:  0.565
BCF:   0.861
?
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:   3.516
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.809
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.131
?
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
NPO8257 Carpha glomerata Species Cyperaceae Eukaryota n.a. n.a. n.a. PMID[30219526]
NPO8257 Carpha glomerata Species Cyperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8257 Carpha glomerata Species Cyperaceae 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
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 3400.0 nM PMID[30219526]

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 NPC480991 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
0.7368 Intermediate Similarity NPC107572
0.7368 Intermediate Similarity NPC32739
0.6981 Remote Similarity NPC603284
0.6462 Remote Similarity NPC166934
0.6066 Remote Similarity NPC76372
0.6066 Remote Similarity NPC37496
0.6032 Remote Similarity NPC66515
0.597 Remote Similarity NPC131579
0.597 Remote Similarity NPC485613
0.5968 Remote Similarity NPC324436
0.5968 Remote Similarity NPC78
0.5873 Remote Similarity NPC148757
0.5789 Remote Similarity NPC32441
0.5789 Remote Similarity NPC79943
0.5775 Remote Similarity NPC296998
0.5775 Remote Similarity NPC473077
0.5625 Remote Similarity NPC265040
0.5614 Remote Similarity NPC213322
0.5588 Remote Similarity NPC69531
0.5538 Remote Similarity NPC220998
0.5522 Remote Similarity NPC161506
0.5522 Remote Similarity NPC485620
0.5517 Remote Similarity NPC482121
0.5517 Remote Similarity NPC270964
0.5507 Remote Similarity NPC131568
0.5479 Remote Similarity NPC285630
0.5469 Remote Similarity NPC306829
0.5424 Remote Similarity NPC167624
0.5424 Remote Similarity NPC166482
0.5373 Remote Similarity NPC291878
0.5362 Remote Similarity NPC278249
0.5362 Remote Similarity NPC223812
0.5352 Remote Similarity NPC485617
0.5312 Remote Similarity NPC164980
0.5303 Remote Similarity NPC480990
0.5246 Remote Similarity NPC485881
0.5246 Remote Similarity NPC469764
0.5217 Remote Similarity NPC473078
0.5211 Remote Similarity NPC479211
0.5167 Remote Similarity NPC4743
0.5143 Remote Similarity NPC24136
0.5139 Remote Similarity NPC488553
0.5082 Remote Similarity NPC329203
0.5082 Remote Similarity NPC324386
0.5082 Remote Similarity NPC222342
0.5075 Remote Similarity NPC470133
0.5072 Remote Similarity NPC36217
0.5068 Remote Similarity NPC224851
0.5068 Remote Similarity NPC479210

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC480991 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
0.5789 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