Natural Product: NPC252960

Natural Product IDNPC252960
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pretazettine
IUPAC Name n.a.
Synonyms Pretazettine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL606758
PubChem CID 10314625
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001775] Amaryllidaceae alkaloids
        • [CHEMONTID:0004124] Tazettine-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 KLJOYDMUWKSYBP-WXNLUCNWSA-N
Standard InCHI InChI=1S/C18H21NO5/c1-19-8-16-18(4-3-10(21-2)5-15(18)19)12-7-14-13(22-9-23-14)6-11(12)17(20)24-16/h3-4,6-7,10,15-17,20H,5,8-9H2,1-2H3/t10-,15+,16+,17?,18+/m1/s1
SMILES CN1C[C@H]2[C@@]3(C=C[C@H](C[C@H]13)OC)c1cc3c(cc1C(O)O2)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   331.14 Volume:   321.504
?
Van der Waals volume.
Dense:   1.03 LogP:   1.089
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.29
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.448
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   24.0
TPSA:   60.39
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.784 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.233 Fsp3:   0.556
MCE-18:   123.429
?
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:   0.331 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.174
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.005
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.518

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.898 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.002 Pgp-substrate:   0.493
PAMPA:   0.947
?
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):   0.003
20% Bioavailability (F20%):   0.177 30% Bioavailability (F30%):   0.073
50% Bioavailability (F50%):   0.944

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.955 MRP1:   0.771
Plasma Protein Binding (PPB):   58.93% Volume Distribution (VD):   0.271
Fu: 41.091%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.429
OATP1B3 inhibitor:   0.563 BCRP inhibitor:   0.05
BSEP inhibitor:   0.13

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.144
CYP2C19-inhibitor:   0.963 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.925 CYP2C9-substrate:   0.943
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.793
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.915
CYP2B6-substrate:   0.977 CYP2C8-inhibitor:   0.0
HLM stability:   0.52
?
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):  5.812 Half-life (T1/2):  2.558

ADMET: Toxicity

hERG Blockers:  0.206 hERG Blockers (10um):  0.574
Human Hepatotoxicity (H-HT):  0.549 Drug-induced Liver Injury (DILI):  0.303
AMES Toxicity:  0.777 Rat Oral Acute Toxicity:  0.799
Maximum Recommended Daily Dose:  0.905 Skin Sensitization:  0.476
Carcinogencity:  0.721 Eye Corrosion:  0.009
Eye Irritation:  0.66 Respiratory Toxicity:  0.88
Drug-induced Neurotoxicity:  0.504 Ototoxicity:  0.386
Hematotoxicity:  0.395 Drug-induced Nephrotoxicity:  0.343
Genotoxicity:  0.905 RPMI-8226 Immunitoxicity:  0.123
A549 Cytotoxicity:  0.055 Hek293 Cytotoxicity:  0.278
BCF:   0.776
?
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:   3.288
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.248
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.176
?
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
NPO33168 amaryllidaceae isoquinoline Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[1336040]
NPO17954 Narcissus tazetta Species Amaryllidaceae Eukaryota n.a. Turkey n.a. PMID[19299148]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[21510636]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. whole plant n.a. PMID[23190013]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota whole plants n.a. n.a. PMID[23190013]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[2348199]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[26913788]
NPO33168 amaryllidaceae isoquinoline Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4166 Pancratium biflorum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9942.1 Narcissus tazetta var. chinensis Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17954 Narcissus tazetta Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4166 Pancratium biflorum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17954 Narcissus tazetta Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9942.1 Narcissus tazetta var. chinensis Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17954 Narcissus tazetta Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7850.1 Schisandra propinqua var. intermedia Varieties Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4166 Pancratium biflorum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9942.1 Narcissus tazetta var. chinensis Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4166 Pancratium biflorum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9927 Crinum asiaticum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17954 Narcissus tazetta 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
NPT341 Organism Punta Toro virus Punta Toro virus IC50 = 0.61 ug.mL-1 PMID[1336040]
NPT33 Organism Japanese encephalitis virus Japanese encephalitis virus IC50 = 0.6 ug.mL-1 PMID[1336040]
NPT4327 Organism Yellow fever virus Yellow fever virus IC50 = 0.5 ug.mL-1 PMID[1336040]
NPT4329 Organism Rift Valley fever virus Rift Valley fever virus IC50 = 2.9 ug.mL-1 PMID[1336040]
NPT4330 Organism Sandfly fever sicilian virus Sandfly fever sicilian virus IC50 = 0.82 ug.mL-1 PMID[1336040]

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 NPC252960 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
0.7031 Intermediate Similarity NPC141440
0.5915 Remote Similarity NPC609368
0.5735 Remote Similarity NPC247972
0.5417 Remote Similarity NPC266176
0.5417 Remote Similarity NPC158148
0.5417 Remote Similarity NPC290759
0.5417 Remote Similarity NPC82533
0.527 Remote Similarity NPC218614
0.527 Remote Similarity NPC607661
0.5211 Remote Similarity NPC78733
0.5205 Remote Similarity NPC225597
0.5065 Remote Similarity NPC479625

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC252960 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