Natural Product: NPC479856

Natural Product IDNPC479856
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HVPDCMMHMJQOAL-ARFHVFGLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14413777
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001775] Amaryllidaceae alkaloids
        • [CHEMONTID:0004120] Lycorine-type amaryllidaceae 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 HVPDCMMHMJQOAL-ARFHVFGLSA-N
Standard InCHI InChI=1S/C16H15NO4/c18-11-3-8-1-2-17-6-9-4-12-13(21-7-20-12)5-10(9)14(15(8)17)16(11)19/h3-5,14-16,19H,1-2,6-7H2/t14-,15+,16+/m0/s1
SMILES C1CN2Cc3cc4c(cc3[C@H]3[C@H]2C1=CC(=O)[C@H]3O)OCO4

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   285.1 Volume:   275.485
?
Van der Waals volume.
Dense:   1.035 LogP:   0.672
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.044
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.088
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   24.0
TPSA:   59.0
?
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:   0.769 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.088 Fsp3:   0.438
MCE-18:   90.217
?
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:   0.639 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.423
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.298
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.341

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.781 MDCK Permeability:   -4.626
Pgp-inhibitor:   0.005 Pgp-substrate:   0.787
PAMPA:   0.754
?
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):   0.009
20% Bioavailability (F20%):   0.106 30% Bioavailability (F30%):   0.098
50% Bioavailability (F50%):   0.787

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.539 MRP1:   0.71
Plasma Protein Binding (PPB):   72.445% Volume Distribution (VD):   0.195
Fu: 30.51%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.865
OATP1B3 inhibitor:   0.956 BCRP inhibitor:   0.021
BSEP inhibitor:   0.912

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.545
CYP2C19-inhibitor:   0.925 CYP2C19-substrate:   0.02
CYP2C9-inhibitor:   0.99 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.951
CYP3A4-inhibitor:   0.094 CYP3A4-substrate:   0.963
CYP2B6-substrate:   0.024 CYP2C8-inhibitor:   0.001
HLM stability:   0.767
?
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):  5.0 Half-life (T1/2):  2.783

ADMET: Toxicity

hERG Blockers:  0.196 hERG Blockers (10um):  0.465
Human Hepatotoxicity (H-HT):  0.692 Drug-induced Liver Injury (DILI):  0.758
AMES Toxicity:  0.811 Rat Oral Acute Toxicity:  0.579
Maximum Recommended Daily Dose:  0.488 Skin Sensitization:  0.936
Carcinogencity:  0.819 Eye Corrosion:  0.002
Eye Irritation:  0.582 Respiratory Toxicity:  0.716
Drug-induced Neurotoxicity:  0.795 Ototoxicity:  0.624
Hematotoxicity:  0.768 Drug-induced Nephrotoxicity:  0.827
Genotoxicity:  0.994 RPMI-8226 Immunitoxicity:  0.148
A549 Cytotoxicity:  0.327 Hek293 Cytotoxicity:  0.512
BCF:   1.033
?
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:   3.533
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.16
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.435
?
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
NPO40778 Alkaloid lycorine Species n.a. n.a. n.a. n.a. n.a. PMID[22019045]

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
NPT81 Cell line A549 Homo sapiens IC50 = 9900.0 nM PMID[19788245]
NPT170 Cell line SK-MEL-28 Homo sapiens IC50 > 10000.0 nM PMID[19788245]
NPT169 Cell line B16-F10 Mus musculus IC50 > 10000.0 nM PMID[19788245]
NPT83 Cell line MCF7 Homo sapiens GI50 = 35000.0 nM PMID[22019045]
NPT169 Cell line B16-F10 Mus musculus GI50 = 16000.0 nM PMID[22019045]
NPT1125 Cell line T98G Homo sapiens GI50 = 38000.0 nM PMID[22019045]
NPT81 Cell line A549 Homo sapiens GI50 = 4000.0 nM PMID[22019045]
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 > 100000.0 nM PMID[22019045]
NPT306 Cell line PC-3 Homo sapiens GI50 = 92000.0 nM PMID[22019045]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 14700.0 nM PMID[20627737]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[19788245]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 3000.0 nM PMID[22019045]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 45000.0 nM PMID[22019045]
NPT25178 Organism Edwardsiella ictaluri Edwardsiella ictaluri MIC > 26.0 ug.mL-1 PMID[29033234]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 26.0 ug.mL-1 PMID[29033234]
NPT1724 Organism Dengue virus Dengue virus EC50 = 400.0 nM PMID[31128447]
NPT24393 Organism Flavobacterium columnare Flavobacterium columnare MIC > 26.0 ug.mL-1 PMID[29033234]

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 NPC479856 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
0.7419 Intermediate Similarity NPC320104
0.7258 Intermediate Similarity NPC190332
0.7258 Intermediate Similarity NPC181653
0.6716 Remote Similarity NPC607721
0.6301 Remote Similarity NPC479857
0.625 Remote Similarity NPC479858
0.6056 Remote Similarity NPC237044
0.6053 Remote Similarity NPC479861
0.5972 Remote Similarity NPC474325
0.5811 Remote Similarity NPC475981
0.5811 Remote Similarity NPC474745
0.5714 Remote Similarity NPC230098
0.5714 Remote Similarity NPC479864
0.5658 Remote Similarity NPC479860
0.5652 Remote Similarity NPC246597
0.5634 Remote Similarity NPC474324
0.5556 Remote Similarity NPC475845
0.5455 Remote Similarity NPC479867
0.5405 Remote Similarity NPC474708
0.5366 Remote Similarity NPC479865
0.5342 Remote Similarity NPC479870
0.5263 Remote Similarity NPC479869
0.5244 Remote Similarity NPC479866
0.5143 Remote Similarity NPC479852
0.5128 Remote Similarity NPC479859
0.5128 Remote Similarity NPC479863

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479856 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