Natural Product: NPC474708

Natural Product IDNPC474708
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XFPKJBMPXIIKGU-ZMUKGBGYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479819
PubChem CID 44570429
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 XFPKJBMPXIIKGU-ZMUKGBGYSA-N
Standard InCHI InChI=1S/C24H29NO6/c1-3-5-20(26)30-19-9-14-7-8-25-12-15-10-17-18(29-13-28-17)11-16(15)22(23(14)25)24(19)31-21(27)6-4-2/h9-11,19,22-24H,3-8,12-13H2,1-2H3/t19-,22-,23+,24+/m0/s1
SMILES CCCC(=O)OC1C=C2CCN3C2C(C1OC(=O)CCC)C4=CC5=C(C=C4C3)OCO5

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   427.2 Volume:   428.797
?
Van der Waals volume.
Dense:   0.996 LogP:   3.865
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.337
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.859
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   25.0
TPSA:   74.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.508 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.255 Fsp3:   0.583
MCE-18:   92.368
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.166 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.457
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.439
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.02

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.609 MDCK Permeability:   -4.758
Pgp-inhibitor:   0.058 Pgp-substrate:   0.956
PAMPA:   0.274
?
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):   0.019
20% Bioavailability (F20%):   0.572 30% Bioavailability (F30%):   0.132
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.935 MRP1:   0.921
Plasma Protein Binding (PPB):   94.726% Volume Distribution (VD):   -0.108
Fu: 4.842%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.674
OATP1B3 inhibitor:   0.94 BCRP inhibitor:   0.002
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.73 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.911 CYP2C19-substrate:   0.089
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.085 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.016 CYP3A4-substrate:   0.72
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.812
HLM stability:   1.0
?
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):  6.372 Half-life (T1/2):  0.591

ADMET: Toxicity

hERG Blockers:  0.153 hERG Blockers (10um):  0.497
Human Hepatotoxicity (H-HT):  0.427 Drug-induced Liver Injury (DILI):  0.382
AMES Toxicity:  0.476 Rat Oral Acute Toxicity:  0.463
Maximum Recommended Daily Dose:  0.744 Skin Sensitization:  0.527
Carcinogencity:  0.824 Eye Corrosion:  0.0
Eye Irritation:  0.022 Respiratory Toxicity:  0.415
Drug-induced Neurotoxicity:  0.739 Ototoxicity:  0.872
Hematotoxicity:  0.285 Drug-induced Nephrotoxicity:  0.729
Genotoxicity:  0.907 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.08 Hek293 Cytotoxicity:  0.296
BCF:   1.214
?
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:   3.892
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.551
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.894
?
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
NPO25024 Lycoris traubii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[19013823]
NPO25024 Lycoris traubii Species Amaryllidaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 0.53 ug.mL-1 PMID[8350092]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 0.67 ug.mL-1 PMID[22591063]
NPT2 Others Unspecified n.a. Ratio IC50 = 21.7 n.a. PMID[17883259]
NPT2 Others Unspecified n.a. Ratio IC50 = 27.5 n.a. PMID[10650080]

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 NPC474708 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
0.9016 High Similarity NPC475845
0.8548 High Similarity NPC474324
0.7917 Intermediate Similarity NPC479862
0.7681 Intermediate Similarity NPC479863
0.7286 Intermediate Similarity NPC474745
0.7143 Intermediate Similarity NPC479869
0.7059 Intermediate Similarity NPC479870
0.6712 Remote Similarity NPC479859
0.6667 Remote Similarity NPC230098
0.6667 Remote Similarity NPC479864
0.662 Remote Similarity NPC237044
0.6528 Remote Similarity NPC474325
0.6351 Remote Similarity NPC475981
0.625 Remote Similarity NPC479865
0.6184 Remote Similarity NPC479857
0.6125 Remote Similarity NPC479866
0.589 Remote Similarity NPC607721
0.5714 Remote Similarity NPC479858
0.5634 Remote Similarity NPC190332
0.5634 Remote Similarity NPC181653
0.557 Remote Similarity NPC479860
0.5405 Remote Similarity NPC479856
0.5375 Remote Similarity NPC479867
0.5366 Remote Similarity NPC479861
0.5342 Remote Similarity NPC320104

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474708 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