Natural Product: NPC563868

Natural Product IDNPC563868
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JACOBINE
IUPAC Name (1~{R},3'~{S},4~{S},6~{R},7~{R},17~{R})-7-hydroxy-3',6,7-trimethyl-spiro[2,9-dioxa-14-azatricyclo[9.5.1.0^{14,17}]heptadec-11-ene-4,2'-oxirane]-3,8-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 IAPHXJRHXBQDQJ-WKMWQDDRSA-N
Standard InCHI InChI=1S/C18H25NO6/c1-10-8-18(11(2)25-18)16(21)24-13-5-7-19-6-4-12(14(13)19)9-23-15(20)17(10,3)22/h4,10-11,13-14,22H,5-9H2,1-3H3/t10-,11+,13-,14-,17-,18+/m1/s1
SMILES C[C@@H]1C[C@@]2(O[C@H]2C)C(=O)O[C@@H]2CCN3CC=C(COC(=O)[C@]1(C)O)[C@H]23

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   351.17 Volume:   341.487
?
Van der Waals volume.
Dense:   1.028 LogP:   0.814
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.208
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.758
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   24.0
TPSA:   88.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.384 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.802 Fsp3:   0.778
MCE-18:   95.875
?
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:   0.112 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.015
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.015
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.006 Promiscuous compounds:   0.695

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.337 MDCK Permeability:   -4.945
Pgp-inhibitor:   0.002 Pgp-substrate:   0.949
PAMPA:   0.922
?
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):   0.013
20% Bioavailability (F20%):   0.573 30% Bioavailability (F30%):   0.869
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.983
Plasma Protein Binding (PPB):   36.869% Volume Distribution (VD):   0.111
Fu: 64.949%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.004
BSEP inhibitor:   0.862

ADMET: Metabolism

CYP1A2-inhibitor:   0.211 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.366 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.06 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.022
CYP3A4-inhibitor:   0.954 CYP3A4-substrate:   0.582
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.513
HLM stability:   0.885
?
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):  4.355 Half-life (T1/2):  3.421

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.36
Human Hepatotoxicity (H-HT):  0.782 Drug-induced Liver Injury (DILI):  0.552
AMES Toxicity:  0.869 Rat Oral Acute Toxicity:  0.712
Maximum Recommended Daily Dose:  0.86 Skin Sensitization:  0.999
Carcinogencity:  0.966 Eye Corrosion:  0.007
Eye Irritation:  0.257 Respiratory Toxicity:  0.396
Drug-induced Neurotoxicity:  0.826 Ototoxicity:  0.296
Hematotoxicity:  0.548 Drug-induced Nephrotoxicity:  0.948
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.23
A549 Cytotoxicity:  0.309 Hek293 Cytotoxicity:  0.394
BCF:   0.446
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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:   3.101
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.482
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.734
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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
NPO64474 Senecio cneraria Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO48075 Senecio viscosus L. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO43807 Senecio rupestris Waldst. & Kit. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO51575 Senecio paludosus L. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58701 Senecio ovatus (P. Gaertn. & al.) Willd. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO48982 Senecio jacobaea L. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO49394 Senecio incarnus Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO43506 Senecio incanus L. s.l. (S. incanus L. s.str., S. incanus subsp. carniolicus (Willd.) Braun-Blanq. and S. incanus subsp. insubricus (Chenevard) Braun-Blanq.) Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO55641 Senecio inaequidens DC. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO57077 Senecio hercynicus Herborg Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO47709 Senecio halleri Dandy Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO48501 Senecio crucifolia Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30147 Senecio cineraria Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61524 Senecio cannabifolius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO55816 Senecio aquaticus Hill Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44185 Senecio alpinus (L.) Scop. Genus Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30299 Senecio alpinus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29999 Senecio jacobaea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30299 Senecio alpinus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30147 Senecio cineraria Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29999 Senecio jacobaea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29999 Senecio jacobaea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30299 Senecio alpinus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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 NPC563868 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 NPC23963
0.75 Intermediate Similarity NPC130124
0.75 Intermediate Similarity NPC193471
0.6935 Remote Similarity NPC608663
0.6615 Remote Similarity NPC316984
0.6462 Remote Similarity NPC47857
0.6462 Remote Similarity NPC181510
0.6462 Remote Similarity NPC168758
0.6462 Remote Similarity NPC602310
0.6364 Remote Similarity NPC201889
0.6364 Remote Similarity NPC106791
0.6364 Remote Similarity NPC607716
0.6308 Remote Similarity NPC608751
0.625 Remote Similarity NPC30911
0.625 Remote Similarity NPC608092
0.6212 Remote Similarity NPC609037
0.5882 Remote Similarity NPC608959
0.5672 Remote Similarity NPC610562
0.5634 Remote Similarity NPC600980
0.5571 Remote Similarity NPC200412
0.5571 Remote Similarity NPC156336
0.5571 Remote Similarity NPC120599

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC563868 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
0.625 Remote Similarity NPD2204 Approved

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