Natural Product: NPC111485

Natural Product IDNPC111485
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Caryachine
IUPAC Name n.a.
Synonyms Caryachine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL480663
PubChem CID 44575219
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002793] Pavine alkaloids

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 TZJNFQHUSMXCIT-GJZGRUSLSA-N
Standard InCHI InChI=1S/C19H19NO4/c1-20-14-4-11-6-18-19(24-9-23-18)8-13(11)15(20)3-10-5-17(22-2)16(21)7-12(10)14/h5-8,14-15,21H,3-4,9H2,1-2H3/t14-,15-/m0/s1
SMILES CN1[C@H]2Cc3cc4c(cc3[C@@H]1Cc1cc(c(cc21)O)OC)OCO4

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   325.13 Volume:   324.737
?
Van der Waals volume.
Dense:   1.001 LogP:   1.952
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.919
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.647
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   51.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.873 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.116 Fsp3:   0.368
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.632 Fluc inhibitor:   0.026
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.87
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.242
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.006 Promiscuous compounds:   0.36

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.919 MDCK Permeability:   -4.716
Pgp-inhibitor:   0.003 Pgp-substrate:   0.52
PAMPA:   0.015
?
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%):   0.882 30% Bioavailability (F30%):   0.584
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.92 MRP1:   0.971
Plasma Protein Binding (PPB):   74.329% Volume Distribution (VD):   -0.148
Fu: 27.038%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.927
OATP1B3 inhibitor:   0.828 BCRP inhibitor:   0.078
BSEP inhibitor:   0.789

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.867 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.473
CYP3A4-inhibitor:   0.993 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.247 CYP2C8-inhibitor:   0.0
HLM stability:   0.002
?
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):  6.641 Half-life (T1/2):  2.125

ADMET: Toxicity

hERG Blockers:  0.421 hERG Blockers (10um):  0.664
Human Hepatotoxicity (H-HT):  0.488 Drug-induced Liver Injury (DILI):  0.209
AMES Toxicity:  0.786 Rat Oral Acute Toxicity:  0.685
Maximum Recommended Daily Dose:  0.888 Skin Sensitization:  0.523
Carcinogencity:  0.848 Eye Corrosion:  0.002
Eye Irritation:  0.245 Respiratory Toxicity:  0.933
Drug-induced Neurotoxicity:  0.801 Ototoxicity:  0.357
Hematotoxicity:  0.269 Drug-induced Nephrotoxicity:  0.439
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.125
A549 Cytotoxicity:  0.347 Hek293 Cytotoxicity:  0.475
BCF:   1.472
?
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:   3.914
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.258
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.55
?
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
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)98060-9]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota n.a. leaf n.a. DOI[10.1016/S0031-9422(98)00534-2]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[12932146]
NPO16174 Scleropyrum wallichianum Species Cervantesiaceae Eukaryota n.a. twig n.a. PMID[16204994]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. Oakham, MA, US n.a. PMID[16562853]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. leaf n.a. PMID[17020288]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[17250743]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota leaves Lai-I, Pingtung County, Taiwan 2005-May PMID[20704331]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. aerial part n.a. PMID[20949916]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota aerial parts n.a. n.a. PMID[20949916]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[22624550]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota aerial parts Nanning, Guangxi Province, China 2014-OCT PMID[28753309]
NPO12301 Chenopodium quinoa Species Chenopodiaceae Eukaryota n.a. n.a. PMID[31861466]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39064968]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12301 Chenopodium quinoa Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15911 Streptomyces graminofaciens Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14366 Youngia japonica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7878 Lysastrosoma anthosticta n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO14485 Eriocephalus kingesii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3521 Geranium collinum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16174 Scleropyrum wallichianum Species Cervantesiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14086 Parthenium confertum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12296 Sphaerechinus granularis Species Toxopneustidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13631 Microglossa pyrifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7036 Davidsonia pruriens Species Cunoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13929 Hypocrella bambusae Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6615 Aplidium solidum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13040 Veretillum cynomorium Species Veretillidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12301 Chenopodium quinoa Species Chenopodiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16174 Scleropyrum wallichianum Species Cervantesiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13929 Hypocrella bambusae Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16174 Scleropyrum wallichianum Species Cervantesiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12064 Lychnophora pinaster Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11277 Baeckea frutescens Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14485 Eriocephalus kingesii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1202 Psathyrotes ramosissima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15311 Cryptocarya chinensis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11607 Marrubium parviflorum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1946 Veronica stricta Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13755 Gonotheca helianthoides n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO7878 Lysastrosoma anthosticta n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO20068 Fusarium striatum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13241 Coprosma foetidissima Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3521 Geranium collinum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14223 Harpullia cupanioides Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13040 Veretillum cynomorium Species Veretillidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26228 Phymatopteris hastata Species Polypodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10936 Andira retusa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14996 Lobelia syphilitica Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1927 Isodon eriocalyx Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6241 Girgensohnia oppositiflora Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14344 Trifolium diffusum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15098 Cyttaria johowii Species Cyttariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14366 Youngia japonica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16090 Panicum crus-galli Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8632 Aralia hispida Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16174 Scleropyrum wallichianum Species Cervantesiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2075 Zanthoxylum ocumarense Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15911 Streptomyces graminofaciens Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO14639 Balanophora polyandra Species Balanophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6615 Aplidium solidum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2770 Pyropolyporus fomentarius n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO12301 Chenopodium quinoa Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14086 Parthenium confertum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12296 Sphaerechinus granularis Species Toxopneustidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13929 Hypocrella bambusae Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15730 Citrus medica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11833 Dyssodia anthemidifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5040 Polygonatum polyanthemum Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6229 Chenopodiastrum murale Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4986 Eschscholzia californica Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12818 Lespedeza maximowiczi Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7036 Davidsonia pruriens Species Cunoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13631 Microglossa pyrifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14885 Lilium rubrum Species Liliaceae 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
NPT92 Individual protein Serotonin 1a (5-HT1a) receptor Homo sapiens EC50 = 9000.0 nM PMID[16562853]
NPT92 Individual protein Serotonin 1a (5-HT1a) receptor Homo sapiens Activity = 5.0 uM PMID[16562853]

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 NPC111485 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
0.8936 High Similarity NPC185467
0.8478 Intermediate Similarity NPC34559
0.766 Intermediate Similarity NPC192768
0.7111 Intermediate Similarity NPC233029
0.7111 Intermediate Similarity NPC210148
0.6786 Remote Similarity NPC90820
0.5373 Remote Similarity NPC232514
0.5231 Remote Similarity NPC606650
0.5152 Remote Similarity NPC276944
0.5152 Remote Similarity NPC238530

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC111485 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