Natural Product: NPC229023

Natural Product IDNPC229023
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YLFKDWVECRVHGB-MJFSBKNWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102294873
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0001775] Amaryllidaceae alkaloids
        • [CHEMONTID:0004128] Galanthamine-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 YLFKDWVECRVHGB-MJFSBKNWSA-N
Standard InCHI InChI=1S/C17H21NO4/c1-18-8-10-3-4-12(21-2)16-15(10)17(13(20)9-18)6-5-11(19)7-14(17)22-16/h3-6,11,13-14,19-20H,7-9H2,1-2H3/t11-,13-,14-,17-/m0/s1
SMILES CN1Cc2ccc(c3c2[C@@]2(C=C[C@@H](C[C@@H]2O3)O)[C@H](C1)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   303.15 Volume:   303.974
?
Van der Waals volume.
Dense:   0.997 LogP:   0.255
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.65
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.73
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   62.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.752 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.735 Fsp3:   0.529
MCE-18:   104.385
?
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:   0.39 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.084
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.027
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.007 Promiscuous compounds:   0.524

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.674 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.054 Pgp-substrate:   0.741
PAMPA:   0.152
?
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%):   0.017 30% Bioavailability (F30%):   0.175
50% Bioavailability (F50%):   0.318

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.997 MRP1:   0.574
Plasma Protein Binding (PPB):   32.302% Volume Distribution (VD):   0.255
Fu: 62.612%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   0.775 BCRP inhibitor:   0.239
BSEP inhibitor:   0.935

ADMET: Metabolism

CYP1A2-inhibitor:   0.026 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.686 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.019 CYP2C9-substrate:   0.071
CYP2D6-inhibitor:   0.899 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.693 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.003
HLM stability:   0.014
?
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):  8.374 Half-life (T1/2):  3.709

ADMET: Toxicity

hERG Blockers:  0.281 hERG Blockers (10um):  0.374
Human Hepatotoxicity (H-HT):  0.726 Drug-induced Liver Injury (DILI):  0.313
AMES Toxicity:  0.521 Rat Oral Acute Toxicity:  0.677
Maximum Recommended Daily Dose:  0.921 Skin Sensitization:  0.727
Carcinogencity:  0.768 Eye Corrosion:  0.016
Eye Irritation:  0.627 Respiratory Toxicity:  0.964
Drug-induced Neurotoxicity:  0.547 Ototoxicity:  0.616
Hematotoxicity:  0.294 Drug-induced Nephrotoxicity:  0.852
Genotoxicity:  0.77 RPMI-8226 Immunitoxicity:  0.122
A549 Cytotoxicity:  0.04 Hek293 Cytotoxicity:  0.203
BCF:   0.29
?
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:   2.725
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.252
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.316
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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
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota whole plants n.a. n.a. PMID[23190013]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. whole plant 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]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10671 Zephyranthes candida Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10671 Zephyranthes candida 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]
NPO10671 Zephyranthes candida 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

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 NPC229023 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 NPC91341
0.7031 Intermediate Similarity NPC148014
0.7031 Intermediate Similarity NPC315707
0.7031 Intermediate Similarity NPC78359
0.6923 Remote Similarity NPC607345
0.6923 Remote Similarity NPC611663
0.6615 Remote Similarity NPC486680
0.6 Remote Similarity NPC40389
0.5833 Remote Similarity NPC65490
0.5507 Remote Similarity NPC305985
0.5507 Remote Similarity NPC129603
0.5507 Remote Similarity NPC56540
0.5143 Remote Similarity NPC284842
0.5068 Remote Similarity NPC479634

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC229023 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
0.7031 Intermediate Similarity NPD2563 Phase 4
0.6923 Remote Similarity NPD2560 Approved
0.5658 Remote Similarity NPD6071 Discontinued

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