Structure

Physi-Chem Properties

Molecular Weight:  818.5
Volume:  845.102
LogP:  3.135
LogD:  2.707
LogS:  -3.771
# Rotatable Bonds:  26
TPSA:  253.13
# H-Bond Aceptor:  15
# H-Bond Donor:  9
# Rings:  1
# Heavy Atoms:  15

MedChem Properties

QED Drug-Likeness Score:  0.05
Synthetic Accessibility Score:  6.136
Fsp3:  0.81
Lipinski Rule-of-5:  Rejected
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  2
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.867
MDCK Permeability:  0.00019499707559589297
Pgp-inhibitor:  1.0
Pgp-substrate:  1.0
Human Intestinal Absorption (HIA):  0.999
20% Bioavailability (F20%):  0.004
30% Bioavailability (F30%):  0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.009
Plasma Protein Binding (PPB):  83.57634735107422%
Volume Distribution (VD):  0.635
Pgp-substrate:  5.258956432342529%

ADMET: Metabolism

CYP1A2-inhibitor:  0.022
CYP1A2-substrate:  0.035
CYP2C19-inhibitor:  0.004
CYP2C19-substrate:  0.374
CYP2C9-inhibitor:  0.0
CYP2C9-substrate:  0.017
CYP2D6-inhibitor:  0.004
CYP2D6-substrate:  0.013
CYP3A4-inhibitor:  0.032
CYP3A4-substrate:  0.188

ADMET: Excretion

Clearance (CL):  2.384
Half-life (T1/2):  0.656

ADMET: Toxicity

hERG Blockers:  0.031
Human Hepatotoxicity (H-HT):  0.975
Drug-inuced Liver Injury (DILI):  0.97
AMES Toxicity:  0.065
Rat Oral Acute Toxicity:  0.039
Maximum Recommended Daily Dose:  0.95
Skin Sensitization:  0.147
Carcinogencity:  0.013
Eye Corrosion:  0.003
Eye Irritation:  0.007
Respiratory Toxicity:  0.336

Download Data

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

  Natural Product: NPC472194

Natural Product ID:  NPC472194
Common Name*:   Nigeglanine
IUPAC Name:   3-methyl-6,7,8,9-tetrahydropyridazino[1,2-a]indazol-10-ium-1-ol
Synonyms:  
Standard InCHIKey:  FAGBILYNJCYFKA-UHFFFAOYSA-O
Standard InCHI:  InChI=1S/C12H14N2O/c1-9-6-11-10(12(15)7-9)8-13-4-2-3-5-14(11)13/h6-8H,2-5H2,1H3/p+1
SMILES:  CC1=CC2=C(C=[N+]3N2CCCC3)C(=C1)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL3344049
PubChem CID:   11277543
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001629] Benzopyrazoles
        • [CHEMONTID:0000080] Indazoles
          • [CHEMONTID:0001856] Pyridazinoindazoles

*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
NPO12297 Nigella sativa Species Ranunculaceae Eukaryota seeds n.a. n.a. PMID[25299458]
NPO12297 Nigella sativa Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO12297 Nigella sativa Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12297 Nigella sativa Species Ranunculaceae 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
NPT65 Cell Line HepG2 Homo sapiens Activity = 8.0 % PMID[470225]

☑ 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 NPC472194 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
0.7 Intermediate Similarity NPC476141
0.6796 Remote Similarity NPC472192
0.6222 Remote Similarity NPC77890
0.6222 Remote Similarity NPC267203
0.6222 Remote Similarity NPC132858
0.6 Remote Similarity NPC25513
0.5714 Remote Similarity NPC214125
0.5714 Remote Similarity NPC320667
0.5604 Remote Similarity NPC63284

  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 NPC472194 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
0.6222 Remote Similarity NPD529 Approved
0.5769 Remote Similarity NPD210 Approved
0.5769 Remote Similarity NPD211 Approved
0.5745 Remote Similarity NPD5115 Clinical (unspecified phase)
0.5698 Remote Similarity NPD3709 Clinical (unspecified phase)

  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