Natural Product: NPC144854

Natural Product IDNPC144854
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CUGAWYNVYRXBFW-ANTZAFMPSA-N
IUPAC Name n.a.
Synonyms 7Alpha-Hydroxyeurycomalactone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1081417
PubChem CID 46878901
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0001125] Steroid lactones

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 CUGAWYNVYRXBFW-ANTZAFMPSA-N
Standard InCHI InChI=1S/C19H26O6/c1-7-5-10(20)16(23)18(3)9(7)6-11(21)19(4)12-8(2)14(25-17(12)24)13(22)15(18)19/h5,8-9,11-16,21-23H,6H2,1-4H3/t8-,9+,11-,12-,13+,14-,15-,16-,18+,19+/m1/s1
SMILES CC1=CC(=O)[C@H]([C@]2([C@H]1C[C@@H](O)[C@@]1([C@@H]2[C@@H](O)[C@H]2[C@@H]([C@@H]1C(=O)O2)C)C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   350.17 Volume:   347.786
?
Van der Waals volume.
Dense:   1.007 LogP:   1.182
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.629
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.966
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   21.0
TPSA:   104.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.548 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.805 Fsp3:   0.789
MCE-18:   76.765
?
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:   0.398 Fluc inhibitor:   0.01
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.229
?
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:   0.332 Promiscuous compounds:   0.427

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.139 MDCK Permeability:   -4.777
Pgp-inhibitor:   0.163 Pgp-substrate:   0.776
PAMPA:   0.978
?
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):   0.08
20% Bioavailability (F20%):   0.275 30% Bioavailability (F30%):   0.366
50% Bioavailability (F50%):   0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.842
Plasma Protein Binding (PPB):   48.769% Volume Distribution (VD):   -0.113
Fu: 55.276%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.02
BSEP inhibitor:   0.827

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.028 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.026
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.477
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.852
HLM stability:   0.101
?
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):  5.656 Half-life (T1/2):  2.864

ADMET: Toxicity

hERG Blockers:  0.017 hERG Blockers (10um):  0.269
Human Hepatotoxicity (H-HT):  0.406 Drug-induced Liver Injury (DILI):  0.378
AMES Toxicity:  0.708 Rat Oral Acute Toxicity:  0.473
Maximum Recommended Daily Dose:  0.441 Skin Sensitization:  0.983
Carcinogencity:  0.806 Eye Corrosion:  0.035
Eye Irritation:  0.591 Respiratory Toxicity:  0.741
Drug-induced Neurotoxicity:  0.27 Ototoxicity:  0.531
Hematotoxicity:  0.515 Drug-induced Nephrotoxicity:  0.812
Genotoxicity:  0.77 RPMI-8226 Immunitoxicity:  0.209
A549 Cytotoxicity:  0.252 Hek293 Cytotoxicity:  0.235
BCF:   0.461
?
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:   3.103
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.815
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.026
?
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 = 6200.0 nM PMID[19919052]
NPT2 Others Unspecified n.a. IC50 = 1500.0 nM PMID[24467387]
NPT2 Others Unspecified n.a. Inhibition > 50.0 % PMID[24467387]

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 NPC144854 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
0.7037 Intermediate Similarity NPC277017
0.7037 Intermediate Similarity NPC610393
0.5965 Remote Similarity NPC192813
0.5424 Remote Similarity NPC19412
0.5424 Remote Similarity NPC210005

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC144854 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