Natural Product: NPC312918

Natural Product IDNPC312918
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VYJUHRAQPIBWNV-GFCCVEGCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1588263
PubChem CID 11957301
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 VYJUHRAQPIBWNV-GFCCVEGCSA-N
Standard InCHI InChI=1S/C18H17NO4/c1-21-14-7-11-10(5-13(14)20)4-12-16-9(2-3-19-12)6-15-18(17(11)16)23-8-22-15/h5-7,12,19-20H,2-4,8H2,1H3/t12-/m1/s1
SMILES COc1cc2c(cc1O)C[C@@H]1c3c2c2OCOc2cc3CCN1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   311.12 Volume:   307.441
?
Van der Waals volume.
Dense:   1.012 LogP:   1.867
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.122
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.894
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   59.95
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.847 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.318 Fsp3:   0.333
MCE-18:   85.417
?
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:   0.884 Fluc inhibitor:   0.288
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.599
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.274
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.27

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.154 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.024 Pgp-substrate:   0.636
PAMPA:   0.06
?
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):   0.001
20% Bioavailability (F20%):   0.128 30% Bioavailability (F30%):   0.151
50% Bioavailability (F50%):   0.956

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.296 MRP1:   0.937
Plasma Protein Binding (PPB):   76.612% Volume Distribution (VD):   -0.083
Fu: 25.323%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.311
BSEP inhibitor:   0.842

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.021
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.981 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.639
CYP3A4-inhibitor:   0.15 CYP3A4-substrate:   0.949
CYP2B6-substrate:   0.993 CYP2C8-inhibitor:   0.0
HLM stability:   0.59
?
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):  4.021 Half-life (T1/2):  1.685

ADMET: Toxicity

hERG Blockers:  0.36 hERG Blockers (10um):  0.645
Human Hepatotoxicity (H-HT):  0.783 Drug-induced Liver Injury (DILI):  0.356
AMES Toxicity:  0.851 Rat Oral Acute Toxicity:  0.577
Maximum Recommended Daily Dose:  0.871 Skin Sensitization:  0.84
Carcinogencity:  0.571 Eye Corrosion:  0.003
Eye Irritation:  0.823 Respiratory Toxicity:  0.889
Drug-induced Neurotoxicity:  0.798 Ototoxicity:  0.522
Hematotoxicity:  0.312 Drug-induced Nephrotoxicity:  0.716
Genotoxicity:  0.642 RPMI-8226 Immunitoxicity:  0.124
A549 Cytotoxicity:  0.203 Hek293 Cytotoxicity:  0.438
BCF:   1.498
?
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:   3.871
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.412
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.552
?
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
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. stem wood n.a. DOI[10.1021/np100247r]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. DOI[10.1080/10412905.2001.9699624]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[10395501]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[10425140]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[11912066]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. PMID[12419922]
NPO6333 Annona glabra Species Annonaceae Eukaryota Fruits n.a. n.a. PMID[15568797]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[18217715]
NPO6333 Annona glabra Species Annonaceae Eukaryota stem Taipei Botanical Garden, Taipei, Taiwan, China 2006-MAR PMID[20828184]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. leaf n.a. PMID[21188975]
NPO6333 Annona glabra Species Annonaceae Eukaryota fruits n.a. n.a. PMID[25499882]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[30813368]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38695450]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38851735]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[9584397]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[9599260]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO24160 Litsea sebifera Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. Database[FooDB]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO24160 Litsea sebifera Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24160 Litsea sebifera Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24160 Litsea sebifera Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29515 Laurus nobilis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24160 Litsea sebifera Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3079 Cassytha filiformis Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6333 Annona glabra Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29515 Laurus nobilis Species Lauraceae 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
NPT1197 Individual protein Huntingtin Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT1038 Individual protein Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 50118.7 nM PubChem BioAssay data set
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 18356.4 nM PubChem BioAssay data set
NPT156 Individual protein Sphingomyelin phosphodiesterase Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT105 Individual protein Muscleblind-like protein 1 Homo sapiens Potency n.a. 17782.8 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 11220.2 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 10000.0 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 8891.4 nM PubChem BioAssay data set
NPT803 Individual protein Flap endonuclease 1 Homo sapiens Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT9 Individual protein DNA polymerase eta Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT54 Individual protein Nonstructural protein 1 Influenza A virus Potency = 22387.2 nM PubChem BioAssay data set
NPT57 Individual protein Induced myeloid leukemia cell differentiation protein Mcl-1 Homo sapiens IC50 = 5612.2 nM PubChem BioAssay data set
NPT888 Individual protein 78 kDa glucose-regulated protein Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 7079.5 nM PubChem BioAssay data set
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 56.2 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set
NPT59 Individual protein DNA polymerase beta Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT63 Individual protein Bromodomain adjacent to zinc finger domain protein 2B Homo sapiens Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 19952.6 nM PubChem BioAssay data set
NPT821 Individual protein Werner syndrome ATP-dependent helicase Homo sapiens Potency n.a. 19952.6 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 23109.3 nM PubChem BioAssay data set
NPT864 Individual protein Lethal(3)malignant brain tumor-like protein 1 Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 631.0 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 14581.0 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 18526.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. EC50 = 13204.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. EC50 = 85585.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. EC50 > 120000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 11582.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. AC50 n.a. 27660.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. AC50 n.a. 84180.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 20596.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 12589.3 nM PubChem BioAssay data set

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 NPC312918 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 NPC155442
0.8276 Intermediate Similarity NPC69712
0.8276 Intermediate Similarity NPC220228
0.7541 Intermediate Similarity NPC6152
0.746 Intermediate Similarity NPC152212
0.746 Intermediate Similarity NPC28341
0.697 Remote Similarity NPC186546
0.6935 Remote Similarity NPC298008
0.6885 Remote Similarity NPC26240
0.6866 Remote Similarity NPC135772
0.6716 Remote Similarity NPC57036
0.6716 Remote Similarity NPC600117
0.6462 Remote Similarity NPC189470
0.6462 Remote Similarity NPC191213
0.6406 Remote Similarity NPC609330
0.6364 Remote Similarity NPC470879
0.597 Remote Similarity NPC302713
0.5714 Remote Similarity NPC481950
0.5507 Remote Similarity NPC192135
0.5373 Remote Similarity NPC203784
0.5373 Remote Similarity NPC170503
0.5373 Remote Similarity NPC126519
0.5224 Remote Similarity NPC66341
0.5217 Remote Similarity NPC610238
0.5205 Remote Similarity NPC600341
0.52 Remote Similarity NPC229166
0.5143 Remote Similarity NPC81247
0.5143 Remote Similarity NPC35627
0.5143 Remote Similarity NPC299687
0.5143 Remote Similarity NPC476573
0.507 Remote Similarity NPC608930

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC312918 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