Structure

Physi-Chem Properties

Molecular Weight:  223.13
Volume:  224.361
LogP:  1.01
LogD:  -0.106
LogS:  -1.49
# Rotatable Bonds:  2
TPSA:  78.92
# H-Bond Aceptor:  5
# H-Bond Donor:  3
# Rings:  2
# Heavy Atoms:  5

MedChem Properties

QED Drug-Likeness Score:  0.665
Synthetic Accessibility Score:  4.476
Fsp3:  0.636
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:  -5.879
MDCK Permeability:  0.0006758950767107308
Pgp-inhibitor:  0.001
Pgp-substrate:  0.73
Human Intestinal Absorption (HIA):  0.273
20% Bioavailability (F20%):  0.005
30% Bioavailability (F30%):  0.008

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.294
Plasma Protein Binding (PPB):  37.17752456665039%
Volume Distribution (VD):  0.713
Pgp-substrate:  62.73676681518555%

ADMET: Metabolism

CYP1A2-inhibitor:  0.019
CYP1A2-substrate:  0.073
CYP2C19-inhibitor:  0.029
CYP2C19-substrate:  0.077
CYP2C9-inhibitor:  0.007
CYP2C9-substrate:  0.429
CYP2D6-inhibitor:  0.307
CYP2D6-substrate:  0.141
CYP3A4-inhibitor:  0.012
CYP3A4-substrate:  0.044

ADMET: Excretion

Clearance (CL):  9.857
Half-life (T1/2):  0.44

ADMET: Toxicity

hERG Blockers:  0.045
Human Hepatotoxicity (H-HT):  0.97
Drug-inuced Liver Injury (DILI):  0.974
AMES Toxicity:  0.007
Rat Oral Acute Toxicity:  0.786
Maximum Recommended Daily Dose:  0.585
Skin Sensitization:  0.832
Carcinogencity:  0.284
Eye Corrosion:  0.004
Eye Irritation:  0.033
Respiratory Toxicity:  0.958

Download Data

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

  Natural Product: NPC3604

Natural Product ID:  NPC3604
Common Name*:   Plumbagine B
IUPAC Name:   (5S,7R,7aR)-3-amino-5-(2-methylprop-1-enyl)-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-7-carboxylic acid
Synonyms:  
Standard InCHIKey:  HTHPXYZWUCIUIR-HLTSFMKQSA-N
Standard InCHI:  InChI=1S/C11H17N3O2/c1-6(2)3-7-4-8(10(15)16)9-5-13-11(12)14(7)9/h3,7-9H,4-5H2,1-2H3,(H2,12,13)(H,15,16)/t7-,8-,9+/m1/s1
SMILES:  CC(=C[C@@H]1C[C@H]([C@H]2N1C(=N)NC2)C(=O)O)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2407427
PubChem CID:   71746250
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000218] Pyrrolidines
        • [CHEMONTID:0001903] Pyrrolidine carboxylic acids and derivatives
          • [CHEMONTID:0002416] Pyrrolidine carboxylic acids

*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
NPO13608 Plumbago zeylanica Species Plumbaginaceae Eukaryota n.a. root n.a. PMID[16078700]
NPO13608 Plumbago zeylanica Species Plumbaginaceae Eukaryota n.a. n.a. n.a. PMID[23848163]
NPO13608 Plumbago zeylanica Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13608 Plumbago zeylanica Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13608 Plumbago zeylanica Species Plumbaginaceae 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
NPT82 Cell Line MDA-MB-231 Homo sapiens IC50 > 10000.0 nM PMID[557335]
NPT461 Cell Line PANC-1 Homo sapiens IC50 > 10000.0 nM PMID[557335]

☑ 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 NPC3604 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
0.9326 High Similarity NPC304455
0.8776 High Similarity NPC471260
0.8737 High Similarity NPC471257
0.8673 High Similarity NPC471258
0.8416 Intermediate Similarity NPC471259
0.7685 Intermediate Similarity NPC147238
0.7679 Intermediate Similarity NPC471261
0.7414 Intermediate Similarity NPC471255
0.7328 Intermediate Similarity NPC471262
0.7172 Intermediate Similarity NPC304454
0.7143 Intermediate Similarity NPC471263
0.6825 Remote Similarity NPC471256
0.6542 Remote Similarity NPC40663
0.6311 Remote Similarity NPC90476
0.6311 Remote Similarity NPC69374
0.6299 Remote Similarity NPC324722
0.6299 Remote Similarity NPC311244
0.6299 Remote Similarity NPC198644
0.6 Remote Similarity NPC133183
0.5982 Remote Similarity NPC472736
0.5954 Remote Similarity NPC261730
0.5893 Remote Similarity NPC476449
0.5847 Remote Similarity NPC271562
0.58 Remote Similarity NPC122471
0.5745 Remote Similarity NPC278881
0.5714 Remote Similarity NPC142761
0.57 Remote Similarity NPC327272
0.5688 Remote Similarity NPC320057
0.5667 Remote Similarity NPC15413
0.5664 Remote Similarity NPC476261
0.5664 Remote Similarity NPC471635
0.5664 Remote Similarity NPC25033
0.5664 Remote Similarity NPC470382
0.5664 Remote Similarity NPC119225
0.5664 Remote Similarity NPC311658
0.5662 Remote Similarity NPC477400
0.5648 Remote Similarity NPC322672
0.5625 Remote Similarity NPC314293
0.5625 Remote Similarity NPC60424
0.5625 Remote Similarity NPC314221
0.562 Remote Similarity NPC472737
0.562 Remote Similarity NPC469388
0.562 Remote Similarity NPC469389
0.56 Remote Similarity NPC320221

  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 NPC3604 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
0.6042 Remote Similarity NPD5382 Phase 2
0.6022 Remote Similarity NPD9201 Clinical (unspecified phase)
0.5926 Remote Similarity NPD5767 Discontinued
0.5862 Remote Similarity NPD6122 Discontinued
0.5833 Remote Similarity NPD3040 Approved
0.5789 Remote Similarity NPD9232 Phase 2
0.5789 Remote Similarity NPD9233 Phase 3
0.5789 Remote Similarity NPD9231 Phase 3
0.5769 Remote Similarity NPD857 Phase 3
0.5729 Remote Similarity NPD9451 Clinical (unspecified phase)
0.5725 Remote Similarity NPD6901 Phase 3
0.5714 Remote Similarity NPD4829 Discontinued
0.5669 Remote Similarity NPD806 Approved
0.5669 Remote Similarity NPD805 Approved
0.562 Remote Similarity NPD4153 Approved
0.5603 Remote Similarity NPD8076 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