Natural Product: NPC7921

Natural Product IDNPC7921
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HXMUCWWCZOMGTO-HMOMASBHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1080702
PubChem CID 44614657
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0002119] Quassinoids

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 HXMUCWWCZOMGTO-HMOMASBHSA-N
Standard InCHI InChI=1S/C20H28O9/c1-6-5-8(21)14(25)18(3)9(6)11(23)16-19(4)13(18)12(24)10(22)7(2)20(19,28)15(26)17(27)29-16/h5,7,9-16,22-26,28H,1-4H3/t7-,9+,10+,11+,12-,13+,14+,15-,16+,18-,19-,20-/m0/s1
SMILES CC1=CC(=O)[C@H]([C@]2([C@H]1[C@@H](O)[C@H]1OC(=O)[C@@H]([C@@]3([C@]1([C@@H]2[C@@H](O)[C@@H]([C@@H]3C)O)C)O)O)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   412.17 Volume:   391.453
?
Van der Waals volume.
Dense:   1.053 LogP:   0.071
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.879
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.24
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   164.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.244 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.517 Fsp3:   0.8
MCE-18:   88.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.387 Fluc inhibitor:   0.005
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.066
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.339 Promiscuous compounds:   0.489

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.979 MDCK Permeability:   -4.568
Pgp-inhibitor:   0.0 Pgp-substrate:   0.991
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):   0.119
20% Bioavailability (F20%):   0.332 30% Bioavailability (F30%):   0.718
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.701
Plasma Protein Binding (PPB):   46.739% Volume Distribution (VD):   -0.238
Fu: 53.331%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.872
OATP1B3 inhibitor:   0.843 BCRP inhibitor:   0.003
BSEP inhibitor:   0.276

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.953 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.07
HLM stability:   0.053
?
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):  1.134 Half-life (T1/2):  3.746

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.134
Human Hepatotoxicity (H-HT):  0.281 Drug-induced Liver Injury (DILI):  0.212
AMES Toxicity:  0.371 Rat Oral Acute Toxicity:  0.327
Maximum Recommended Daily Dose:  0.297 Skin Sensitization:  0.967
Carcinogencity:  0.053 Eye Corrosion:  0.001
Eye Irritation:  0.685 Respiratory Toxicity:  0.694
Drug-induced Neurotoxicity:  0.009 Ototoxicity:  0.945
Hematotoxicity:  0.391 Drug-induced Nephrotoxicity:  0.899
Genotoxicity:  0.777 RPMI-8226 Immunitoxicity:  0.293
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.02
BCF:   0.334
?
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:   3.033
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.669
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.799
?
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
NPO14602 Vitex negundo Species Lamiaceae Eukaryota leaves n.a. n.a. PMID[12828478]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota Roots n.a. n.a. PMID[14575431]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. root n.a. PMID[15520511]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota seeds n.a. n.a. PMID[15620254]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota seeds n.a. n.a. PMID[1624939]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[17027268]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. root n.a. PMID[1800638]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota roots n.a. n.a. PMID[19299148]
NPO11530 Heterosigma akashiwo Species Chattonellaceae Eukaryota n.a. n.a. n.a. PMID[19659728]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota Seeds n.a. n.a. PMID[19715321]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[19919052]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota Seeds n.a. n.a. PMID[19931461]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[23403897]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[24467387]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota roots n.a. n.a. PMID[25066952]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. PMID[25905468]
NPO5401 Monanchora unguiculata Species Crambeidae Eukaryota n.a. n.a. n.a. PMID[28368118]
NPO9644 Euphorbia resinifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[29667820]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38163555]
NPO13494 Prosopis kuntzei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11530 Heterosigma akashiwo Species Chattonellaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20318 Acinetobacter baumannii Species Moraxellaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO8220 Russula sardonia Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20383 Stenocereus thurberi Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9024 Aralidium pinnatifidum Species Torricelliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9644 Euphorbia resinifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5401 Monanchora unguiculata Species Crambeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO893 Helichrysum sutherlandii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3924 Penicillium alutaceum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13604 Dermocybe cardinalis Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12988 Blainvillea latifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9644 Euphorbia resinifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO893 Helichrysum sutherlandii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9644 Euphorbia resinifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11072 Geigeria schinzii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9965 Eurycoma longifolia Species Simaroubaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11530 Heterosigma akashiwo Species Chattonellaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3924 Penicillium alutaceum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3576 Bersama swinnyi Species Melianthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14280 Helichrysum angustifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6014 Goniothalamus undulatus Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8220 Russula sardonia Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5401 Monanchora unguiculata Species Crambeidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20318 Acinetobacter baumannii Species Moraxellaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO6626 Pteris spinulosa Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2084 Acinetobacter calcoaceticus Species Moraxellaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO1418 Boletinus paluster Species Gyrodontaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13604 Dermocybe cardinalis Species Cortinariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9024 Aralidium pinnatifidum Species Torricelliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9644 Euphorbia resinifera Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8820 Lophocereus marginatus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12577 Pinus glauca Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13692 Leontice kiangnanensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14602 Vitex negundo Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12026 Papaver radicatum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2505 Pachycereus pringlei Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20383 Stenocereus thurberi Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9375 Medium grandiflorum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO893 Helichrysum sutherlandii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13494 Prosopis kuntzei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13798 Cheilanthes marantae Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22888 Lophiostoma vaginatispora Species Lophiostomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12890 Ophryosporus charua Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8640 Nemuaron humboldtii Species Atherospermataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12988 Blainvillea latifolia Species Asteraceae 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
NPT453 Cell line HT-1080 Homo sapiens IC50 = 90000.0 nM PMID[19919052]

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 NPC7921 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
0.6441 Remote Similarity NPC208998
0.5763 Remote Similarity NPC3316
0.5522 Remote Similarity NPC122033
0.5156 Remote Similarity NPC251310

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC7921 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