Structure

Physi-Chem Properties

Molecular Weight:  208.16
Volume:  230.426
LogP:  1.266
LogD:  0.958
LogS:  0.096
# Rotatable Bonds:  3
TPSA:  32.34
# H-Bond Aceptor:  3
# H-Bond Donor:  1
# Rings:  1
# Heavy Atoms:  3

MedChem Properties

QED Drug-Likeness Score:  0.548
Synthetic Accessibility Score:  3.782
Fsp3:  0.583
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.652
MDCK Permeability:  2.0854169633821584e-05
Pgp-inhibitor:  0.013
Pgp-substrate:  0.166
Human Intestinal Absorption (HIA):  0.011
20% Bioavailability (F20%):  0.118
30% Bioavailability (F30%):  0.329

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.481
Plasma Protein Binding (PPB):  46.24004364013672%
Volume Distribution (VD):  1.172
Pgp-substrate:  67.37275695800781%

ADMET: Metabolism

CYP1A2-inhibitor:  0.018
CYP1A2-substrate:  0.09
CYP2C19-inhibitor:  0.034
CYP2C19-substrate:  0.874
CYP2C9-inhibitor:  0.004
CYP2C9-substrate:  0.251
CYP2D6-inhibitor:  0.009
CYP2D6-substrate:  0.87
CYP3A4-inhibitor:  0.008
CYP3A4-substrate:  0.175

ADMET: Excretion

Clearance (CL):  3.535
Half-life (T1/2):  0.357

ADMET: Toxicity

hERG Blockers:  0.063
Human Hepatotoxicity (H-HT):  0.979
Drug-inuced Liver Injury (DILI):  0.341
AMES Toxicity:  0.482
Rat Oral Acute Toxicity:  0.924
Maximum Recommended Daily Dose:  0.844
Skin Sensitization:  0.96
Carcinogencity:  0.893
Eye Corrosion:  0.542
Eye Irritation:  0.145
Respiratory Toxicity:  0.951

Download Data

Data Type Select
General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC470738

Natural Product ID:  NPC470738
Common Name*:   Nigragillin
IUPAC Name:   (2E,4E)-1-[(2R,5S)-2,5-dimethylpiperazin-1-yl]hexa-2,4-dien-1-one
Synonyms:   Nigragillin
Standard InCHIKey:  NHTCAHYQNDAZCU-APDXDPTBSA-N
Standard InCHI:  InChI=1S/C12H20N2O/c1-4-5-6-7-12(15)14-9-10(2)13-8-11(14)3/h4-7,10-11,13H,8-9H2,1-3H3/b5-4+,7-6+/t10-,11+/m0/s1
SMILES:  CC=CC=CC(=O)N1CC(NCC1C)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2208202
PubChem CID:   71454343
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002389] Diazinanes
        • [CHEMONTID:0000189] Piperazines

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  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[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 NP ID 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT139 Cell Line HT-29 Homo sapiens IC50 > 10000.0 nM PMID[527289]
NPT65 Cell Line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[527289]
NPT81 Cell Line A549 Homo sapiens IC50 > 10000.0 nM PMID[527289]
NPT111 Cell Line K562 Homo sapiens IC50 > 10000.0 nM PMID[527289]
NPT116 Cell Line HL-60 Homo sapiens IC50 > 10000.0 nM PMID[527289]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC470738 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.697 Remote Similarity NPC42477
0.6667 Remote Similarity NPC206660
0.6538 Remote Similarity NPC267203
0.6538 Remote Similarity NPC77890
0.6538 Remote Similarity NPC132858
0.6418 Remote Similarity NPC385
0.6389 Remote Similarity NPC76869
0.6389 Remote Similarity NPC477460
0.6324 Remote Similarity NPC133923
0.6282 Remote Similarity NPC25513
0.6154 Remote Similarity NPC320667
0.6154 Remote Similarity NPC214125
0.6143 Remote Similarity NPC252684
0.6026 Remote Similarity NPC63284
0.5897 Remote Similarity NPC78562
0.5897 Remote Similarity NPC473588
0.5694 Remote Similarity NPC477459
0.5694 Remote Similarity NPC477461
0.5679 Remote Similarity NPC86452
0.5679 Remote Similarity NPC244256
0.5625 Remote Similarity NPC34672

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470738 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6538 Remote Similarity NPD529 Approved
0.5763 Remote Similarity NPD1463 Clinical (unspecified phase)
0.5641 Remote Similarity NPD9432 Discontinued

  Bioactivity similarity: Similar Natural Products in NPASS

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