Natural Product: NPC130124

Natural Product IDNPC130124
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Integerrimine
IUPAC Name n.a.
Synonyms Integerrimine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL488203
PubChem CID 5281733
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues

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 HKODIGSRFALUTA-IKZAEVNJSA-N
Standard InCHI InChI=1S/C18H25NO5/c1-4-12-9-11(2)18(3,22)17(21)23-10-13-5-7-19-8-6-14(15(13)19)24-16(12)20/h4-5,11,14-15,22H,6-10H2,1-3H3/b12-4+/t11-,14-,15-,18-/m1/s1
SMILES C/C=C/1C[C@@H](C)[C@](C)(C(=O)OCC2=CCN3CC[C@H]([C@@H]23)OC1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   335.17 Volume:   338.617
?
Van der Waals volume.
Dense:   0.99 LogP:   0.617
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.897
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.427
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   76.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.407 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.044 Fsp3:   0.667
MCE-18:   52.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.097 Fluc inhibitor:   0.046
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.024
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.008 Promiscuous compounds:   0.414

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.112 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.032 Pgp-substrate:   0.715
PAMPA:   0.939
?
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%):   0.018 30% Bioavailability (F30%):   0.327
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.96
Plasma Protein Binding (PPB):   50.036% Volume Distribution (VD):   0.129
Fu: 54.996%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.335
BSEP inhibitor:   0.883

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.021 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.014
CYP3A4-inhibitor:   0.516 CYP3A4-substrate:   0.023
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.185
HLM stability:   0.479
?
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):  4.3 Half-life (T1/2):  2.778

ADMET: Toxicity

hERG Blockers:  0.034 hERG Blockers (10um):  0.14
Human Hepatotoxicity (H-HT):  0.611 Drug-induced Liver Injury (DILI):  0.332
AMES Toxicity:  0.354 Rat Oral Acute Toxicity:  0.426
Maximum Recommended Daily Dose:  0.849 Skin Sensitization:  0.996
Carcinogencity:  0.812 Eye Corrosion:  0.007
Eye Irritation:  0.118 Respiratory Toxicity:  0.18
Drug-induced Neurotoxicity:  0.332 Ototoxicity:  0.504
Hematotoxicity:  0.411 Drug-induced Nephrotoxicity:  0.917
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.188
A549 Cytotoxicity:  0.055 Hek293 Cytotoxicity:  0.229
BCF:   0.487
?
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:   3.134
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.582
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.885
?
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
NPO33066 senecio anonymus Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[3210016]
NPO24828 Pteraster tesselatus Species Pterasteridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25503 Anticarsia gemmatalis Species Noctuidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22639 Asterias troscheli Species Asteriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23816 Sideritis ilicifolia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20767 Hydnum imbricatum Species Hydnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23012 Schizogyne glaberrima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23297 Ruilopezia jahnii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19820 Calonectria decora Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24274 Adenophora stenanthina Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22775 Lecanora dispersa Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2561 Capnella erecta Species Nephtheidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24828 Pteraster tesselatus Species Pterasteridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28958 Dugaldia integrifolia n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO18149 Linum paniculatum Species Linaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28452 Rhododendron linearifolium Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25564 Ficus erecta Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25257 Menispermum fenestratum Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17735 Acinetobacter genospecies Species Moraxellaceae Bacteria 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
NPT2319 Cell line A204 Homo sapiens IC50 = 120.0 ug.mL-1 PMID[3210016]
NPT1161 Cell line CHO Cricetulus griseus EC50 > 100.0 ug.mL-1 DOI[10.1016/jbse.2007.08.015]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Activity = 89.0 % DOI[10.1016/jbse.2007.08.015]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Activity = 88.0 % DOI[10.1016/jbse.2007.08.015]
NPT776 Organism Spodoptera littoralis Spodoptera littoralis EC50 > 100.0 microg/cm2 DOI[10.1016/jbse.2007.08.015]
NPT364 Organism Lactuca sativa Lactuca sativa Inhibition < 50.0 % DOI[10.1016/jbse.2007.08.015]
NPT2528 Organism Rhopalosiphum padi Rhopalosiphum padi Activity = 43.0 % DOI[10.1016/jbse.2007.08.015]
NPT1275 Organism Leptinotarsa decemlineata Leptinotarsa decemlineata EC50 = 3.4 microg/cm2 DOI[10.1016/jbse.2007.08.015]
NPT348 Organism Myzus persicae Myzus persicae Activity = 57.0 % DOI[10.1016/jbse.2007.08.015]

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 NPC130124 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 NPC193471
0.8421 Intermediate Similarity NPC201889
0.8421 Intermediate Similarity NPC106791
0.8421 Intermediate Similarity NPC607716
0.7931 Intermediate Similarity NPC47857
0.7931 Intermediate Similarity NPC181510
0.7931 Intermediate Similarity NPC168758
0.7931 Intermediate Similarity NPC602310
0.7586 Intermediate Similarity NPC608663
0.75 Intermediate Similarity NPC23963
0.7167 Intermediate Similarity NPC608751
0.7049 Intermediate Similarity NPC609037
0.6667 Remote Similarity NPC608959
0.6557 Remote Similarity NPC30911
0.6557 Remote Similarity NPC608092
0.6406 Remote Similarity NPC316984
0.6364 Remote Similarity NPC600980
0.6 Remote Similarity NPC235625
0.5522 Remote Similarity NPC195435
0.5522 Remote Similarity NPC196073
0.5224 Remote Similarity NPC610562

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC130124 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
0.6557 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