Structure

Physi-Chem Properties

Molecular Weight:  311.18
Volume:  311.125
LogP:  0.407
LogD:  -0.162
LogS:  -0.966
# Rotatable Bonds:  6
TPSA:  108.09
# H-Bond Aceptor:  7
# H-Bond Donor:  4
# Rings:  2
# Heavy Atoms:  7

MedChem Properties

QED Drug-Likeness Score:  0.518
Synthetic Accessibility Score:  4.7
Fsp3:  0.733
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:  -6.266
MDCK Permeability:  0.001411652541719377
Pgp-inhibitor:  0.001
Pgp-substrate:  0.982
Human Intestinal Absorption (HIA):  0.956
20% Bioavailability (F20%):  0.228
30% Bioavailability (F30%):  0.385

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.075
Plasma Protein Binding (PPB):  16.585054397583008%
Volume Distribution (VD):  0.69
Pgp-substrate:  74.03109741210938%

ADMET: Metabolism

CYP1A2-inhibitor:  0.008
CYP1A2-substrate:  0.047
CYP2C19-inhibitor:  0.023
CYP2C19-substrate:  0.059
CYP2C9-inhibitor:  0.007
CYP2C9-substrate:  0.556
CYP2D6-inhibitor:  0.061
CYP2D6-substrate:  0.138
CYP3A4-inhibitor:  0.008
CYP3A4-substrate:  0.012

ADMET: Excretion

Clearance (CL):  2.41
Half-life (T1/2):  0.856

ADMET: Toxicity

hERG Blockers:  0.025
Human Hepatotoxicity (H-HT):  0.992
Drug-inuced Liver Injury (DILI):  0.976
AMES Toxicity:  0.005
Rat Oral Acute Toxicity:  0.089
Maximum Recommended Daily Dose:  0.888
Skin Sensitization:  0.911
Carcinogencity:  0.432
Eye Corrosion:  0.005
Eye Irritation:  0.086
Respiratory Toxicity:  0.943

Download Data

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

  Natural Product: NPC471260

Natural Product ID:  NPC471260
Common Name*:   Plumbagine F
IUPAC Name:   (5S,7R,7aR)-2-(2,4-dihydroxybutyl)-3-imino-5-(2-methylprop-1-enyl)-5,6,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-7-carboxylic acid
Synonyms:  
Standard InCHIKey:  VXIDNRDRDTVAPE-ODWCKFRGSA-N
Standard InCHI:  InChI=1S/C15H25N3O4/c1-9(2)5-10-6-12(14(21)22)13-8-17(15(16)18(10)13)7-11(20)3-4-19/h5,10-13,16,19-20H,3-4,6-8H2,1-2H3,(H,21,22)/t10-,11?,12-,13+/m1/s1
SMILES:  OCCC(CN1C[C@@H]2N(C1=N)[C@@H](C[C@H]2C(=O)O)C=C(C)C)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2407431
PubChem CID:   71746445
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[509347]
NPT461 Cell Line PANC-1 Homo sapiens IC50 > 10000.0 nM PMID[509347]

☑ 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 NPC471260 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
0.9286 High Similarity NPC471258
0.901 High Similarity NPC471259
0.8776 High Similarity NPC3604
0.8407 Intermediate Similarity NPC471255
0.8218 Intermediate Similarity NPC471257
0.8214 Intermediate Similarity NPC471261
0.8163 Intermediate Similarity NPC304455
0.7845 Intermediate Similarity NPC471262
0.7647 Intermediate Similarity NPC471263
0.7589 Intermediate Similarity NPC147238
0.7302 Intermediate Similarity NPC471256
0.6522 Remote Similarity NPC80439
0.6522 Remote Similarity NPC279833
0.6522 Remote Similarity NPC173690
0.6496 Remote Similarity NPC271562
0.6466 Remote Similarity NPC64168
0.6449 Remote Similarity NPC304454
0.6379 Remote Similarity NPC6271
0.6279 Remote Similarity NPC309525
0.624 Remote Similarity NPC235625
0.6222 Remote Similarity NPC477400
0.6207 Remote Similarity NPC188785
0.6195 Remote Similarity NPC40663
0.6165 Remote Similarity NPC261730
0.6148 Remote Similarity NPC316984
0.6148 Remote Similarity NPC30911
0.6094 Remote Similarity NPC315188
0.6045 Remote Similarity NPC120335
0.6017 Remote Similarity NPC475149
0.6017 Remote Similarity NPC471097
0.6016 Remote Similarity NPC476875
0.6015 Remote Similarity NPC311244
0.6015 Remote Similarity NPC324722
0.6015 Remote Similarity NPC198644
0.6 Remote Similarity NPC324506
0.6 Remote Similarity NPC477401
0.6 Remote Similarity NPC477399
0.5984 Remote Similarity NPC201889
0.5984 Remote Similarity NPC106791
0.5968 Remote Similarity NPC314550
0.5966 Remote Similarity NPC476877
0.5966 Remote Similarity NPC265094
0.5963 Remote Similarity NPC69374
0.5963 Remote Similarity NPC90476
0.5963 Remote Similarity NPC469363
0.5962 Remote Similarity NPC233108
0.5944 Remote Similarity NPC477519
0.592 Remote Similarity NPC130124
0.592 Remote Similarity NPC193471
0.5913 Remote Similarity NPC119225
0.5913 Remote Similarity NPC471635
0.5913 Remote Similarity NPC25033
0.5913 Remote Similarity NPC476261
0.5913 Remote Similarity NPC150041
0.5913 Remote Similarity NPC470382
0.5902 Remote Similarity NPC15413
0.5902 Remote Similarity NPC171734
0.5897 Remote Similarity NPC475758
0.5873 Remote Similarity NPC103391
0.5873 Remote Similarity NPC472536
0.5868 Remote Similarity NPC476876
0.5856 Remote Similarity NPC52533
0.5847 Remote Similarity NPC475791
0.5847 Remote Similarity NPC13175
0.5846 Remote Similarity NPC314293
0.584 Remote Similarity NPC276995
0.584 Remote Similarity NPC76660
0.5828 Remote Similarity NPC327517
0.5828 Remote Similarity NPC319334
0.5828 Remote Similarity NPC322372
0.5812 Remote Similarity NPC476344
0.5804 Remote Similarity NPC142761
0.5781 Remote Similarity NPC209734
0.5772 Remote Similarity NPC207820
0.5769 Remote Similarity NPC139867
0.576 Remote Similarity NPC181510
0.576 Remote Similarity NPC168758
0.576 Remote Similarity NPC47857
0.5736 Remote Similarity NPC284656
0.5726 Remote Similarity NPC476449
0.5725 Remote Similarity NPC23963
0.5692 Remote Similarity NPC470788
0.5635 Remote Similarity NPC59249
0.5635 Remote Similarity NPC58281
0.5625 Remote Similarity NPC469860
0.5625 Remote Similarity NPC130436
0.5625 Remote Similarity NPC469861
0.5621 Remote Similarity NPC317377
0.5621 Remote Similarity NPC321485
0.562 Remote Similarity NPC473289
0.5616 Remote Similarity NPC315266
0.561 Remote Similarity NPC236644

  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 NPC471260 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
0.6379 Remote Similarity NPD6122 Discontinued
0.637 Remote Similarity NPD5767 Discontinued
0.6299 Remote Similarity NPD1748 Approved
0.6148 Remote Similarity NPD2204 Approved
0.6018 Remote Similarity NPD5781 Clinical (unspecified phase)
0.6016 Remote Similarity NPD805 Approved
0.6016 Remote Similarity NPD806 Approved
0.5906 Remote Similarity NPD6935 Phase 3
0.5906 Remote Similarity NPD6936 Clinical (unspecified phase)
0.5891 Remote Similarity NPD2645 Approved
0.5877 Remote Similarity NPD1706 Clinical (unspecified phase)
0.5814 Remote Similarity NPD2132 Phase 3
0.5812 Remote Similarity NPD8038 Phase 2
0.5806 Remote Similarity NPD1805 Phase 2
0.5806 Remote Similarity NPD1804 Phase 2
0.5802 Remote Similarity NPD1806 Approved
0.5789 Remote Similarity NPD3677 Clinical (unspecified phase)
0.5769 Remote Similarity NPD1689 Approved
0.5738 Remote Similarity NPD1428 Phase 2
0.5703 Remote Similarity NPD869 Approved
0.5692 Remote Similarity NPD3159 Discontinued
0.5672 Remote Similarity NPD4816 Clinical (unspecified phase)
0.5641 Remote Similarity NPD7841 Clinical (unspecified phase)
0.562 Remote Similarity NPD3588 Discontinued
0.5615 Remote Similarity NPD6918 Phase 1
0.5615 Remote Similarity NPD1773 Discontinued
0.5603 Remote Similarity NPD4153 Approved

  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