Structure

Physi-Chem Properties

Molecular Weight:  290.2
Volume:  308.583
LogP:  1.892
LogD:  1.704
LogS:  -1.616
# Rotatable Bonds:  4
TPSA:  41.9
# H-Bond Aceptor:  4
# H-Bond Donor:  0
# Rings:  3
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.75
Synthetic Accessibility Score:  4.259
Fsp3:  0.765
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:  -4.668
MDCK Permeability:  5.751282151322812e-05
Pgp-inhibitor:  0.24
Pgp-substrate:  0.047
Human Intestinal Absorption (HIA):  0.018
20% Bioavailability (F20%):  0.583
30% Bioavailability (F30%):  0.401

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.865
Plasma Protein Binding (PPB):  35.956356048583984%
Volume Distribution (VD):  1.617
Pgp-substrate:  67.70823669433594%

ADMET: Metabolism

CYP1A2-inhibitor:  0.075
CYP1A2-substrate:  0.093
CYP2C19-inhibitor:  0.024
CYP2C19-substrate:  0.801
CYP2C9-inhibitor:  0.006
CYP2C9-substrate:  0.061
CYP2D6-inhibitor:  0.896
CYP2D6-substrate:  0.884
CYP3A4-inhibitor:  0.017
CYP3A4-substrate:  0.455

ADMET: Excretion

Clearance (CL):  8.849
Half-life (T1/2):  0.424

ADMET: Toxicity

hERG Blockers:  0.046
Human Hepatotoxicity (H-HT):  0.764
Drug-inuced Liver Injury (DILI):  0.069
AMES Toxicity:  0.098
Rat Oral Acute Toxicity:  0.39
Maximum Recommended Daily Dose:  0.93
Skin Sensitization:  0.928
Carcinogencity:  0.925
Eye Corrosion:  0.003
Eye Irritation:  0.015
Respiratory Toxicity:  0.952

Download Data

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

  Natural Product: NPC476449

Natural Product ID:  NPC476449
Common Name*:   Grandisine G
IUPAC Name:   methyl 2-[(2S,4S)-6-(1,2,3,5,6,8a-hexahydroindolizin-8-yl)-4-methyl-2,3,4,5-tetrahydropyridin-2-yl]acetate
Synonyms:   Grandisine G
Standard InCHIKey:  FOKUWLHFPJKDKM-VORVDWIASA-N
Standard InCHI:  InChI=1S/C17H26N2O2/c1-12-9-13(11-17(20)21-2)18-15(10-12)14-5-3-7-19-8-4-6-16(14)19/h5,12-13,16H,3-4,6-11H2,1-2H3/t12-,13-,16?/m0/s1
SMILES:  CC1CC(N=C(C1)C2=CCCN3C2CCC3)CC(=O)OC
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL611496
PubChem CID:   16086545
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000089] Pyridines and derivatives
        • [CHEMONTID:0002224] Hydropyridines
          • [CHEMONTID:0001934] Tetrahydropyridines

*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
NPO9570 Elaeocarpus grandis Species Elaeocarpaceae Eukaryota n.a. Australian rainforest n.a. PMID[16989522]

☑ 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
NPT271 Individual Protein Delta opioid receptor Homo sapiens IC50 = 75400.0 nM PMID[490714]

☑ 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 NPC476449 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
0.68 Remote Similarity NPC76283
0.6581 Remote Similarity NPC469423
0.6574 Remote Similarity NPC241426
0.6518 Remote Similarity NPC119329
0.6518 Remote Similarity NPC133420
0.6396 Remote Similarity NPC474348
0.6389 Remote Similarity NPC469424
0.6379 Remote Similarity NPC63511
0.6372 Remote Similarity NPC87919
0.6316 Remote Similarity NPC86906
0.6299 Remote Similarity NPC311244
0.6299 Remote Similarity NPC469387
0.6299 Remote Similarity NPC324722
0.6299 Remote Similarity NPC198644
0.6283 Remote Similarity NPC215988
0.6275 Remote Similarity NPC477584
0.6273 Remote Similarity NPC476344
0.6261 Remote Similarity NPC467022
0.6261 Remote Similarity NPC271562
0.6239 Remote Similarity NPC150041
0.6207 Remote Similarity NPC15413
0.6174 Remote Similarity NPC233256
0.6174 Remote Similarity NPC195841
0.6168 Remote Similarity NPC47230
0.6168 Remote Similarity NPC17143
0.6147 Remote Similarity NPC477290
0.6134 Remote Similarity NPC469968
0.6134 Remote Similarity NPC80834
0.6129 Remote Similarity NPC315188
0.6126 Remote Similarity NPC4834
0.6126 Remote Similarity NPC472736
0.6121 Remote Similarity NPC176773
0.6095 Remote Similarity NPC469860
0.6095 Remote Similarity NPC469861
0.6095 Remote Similarity NPC130436
0.6087 Remote Similarity NPC477519
0.6078 Remote Similarity NPC477582
0.6077 Remote Similarity NPC261730
0.6071 Remote Similarity NPC140685
0.6068 Remote Similarity NPC70235
0.6068 Remote Similarity NPC470535
0.6068 Remote Similarity NPC207820
0.605 Remote Similarity NPC58281
0.605 Remote Similarity NPC79238
0.605 Remote Similarity NPC476875
0.6038 Remote Similarity NPC324506
0.6038 Remote Similarity NPC473525
0.6019 Remote Similarity NPC477583
0.6019 Remote Similarity NPC477581
0.6018 Remote Similarity NPC128698
0.6018 Remote Similarity NPC239768
0.6017 Remote Similarity NPC470536
0.6 Remote Similarity NPC265094
0.5963 Remote Similarity NPC476064
0.5946 Remote Similarity NPC476261
0.5946 Remote Similarity NPC470382
0.5946 Remote Similarity NPC25033
0.5946 Remote Similarity NPC119225
0.5946 Remote Similarity NPC471635
0.5943 Remote Similarity NPC322672
0.5942 Remote Similarity NPC142761
0.5932 Remote Similarity NPC171734
0.5926 Remote Similarity NPC249312
0.5893 Remote Similarity NPC3604
0.5893 Remote Similarity NPC123141
0.5887 Remote Similarity NPC476952
0.5882 Remote Similarity NPC469389
0.5882 Remote Similarity NPC472737
0.5882 Remote Similarity NPC469388
0.5877 Remote Similarity NPC477964
0.5872 Remote Similarity NPC477288
0.5872 Remote Similarity NPC474964
0.5865 Remote Similarity NPC224072
0.5862 Remote Similarity NPC476877
0.5849 Remote Similarity NPC319913
0.5833 Remote Similarity NPC472313
0.5818 Remote Similarity NPC72183
0.5818 Remote Similarity NPC299808
0.5818 Remote Similarity NPC314500
0.5818 Remote Similarity NPC110875
0.5818 Remote Similarity NPC118844
0.5806 Remote Similarity NPC209734
0.5806 Remote Similarity NPC147707
0.5806 Remote Similarity NPC57420
0.5794 Remote Similarity NPC88190
0.5789 Remote Similarity NPC234542
0.5784 Remote Similarity NPC469492
0.578 Remote Similarity NPC304455
0.5776 Remote Similarity NPC152718
0.5776 Remote Similarity NPC226509
0.5776 Remote Similarity NPC247060
0.5776 Remote Similarity NPC50815
0.5772 Remote Similarity NPC471645
0.5763 Remote Similarity NPC476876
0.5763 Remote Similarity NPC154601
0.5763 Remote Similarity NPC271269
0.576 Remote Similarity NPC471673
0.576 Remote Similarity NPC174463
0.5755 Remote Similarity NPC269398
0.5755 Remote Similarity NPC277918
0.5755 Remote Similarity NPC263493
0.5748 Remote Similarity NPC23963
0.5739 Remote Similarity NPC473224
0.5738 Remote Similarity NPC474452
0.5736 Remote Similarity NPC213126
0.5736 Remote Similarity NPC84281
0.5736 Remote Similarity NPC169485
0.5736 Remote Similarity NPC317474
0.5736 Remote Similarity NPC291027
0.5728 Remote Similarity NPC216090
0.5728 Remote Similarity NPC469517
0.5726 Remote Similarity NPC33742
0.5726 Remote Similarity NPC471260
0.5726 Remote Similarity NPC470538
0.5714 Remote Similarity NPC251330
0.5703 Remote Similarity NPC472458
0.5702 Remote Similarity NPC265662
0.57 Remote Similarity NPC306928
0.57 Remote Similarity NPC166797
0.5692 Remote Similarity NPC309525
0.569 Remote Similarity NPC77703
0.569 Remote Similarity NPC188785
0.5688 Remote Similarity NPC34754
0.568 Remote Similarity NPC201968
0.5678 Remote Similarity NPC469958
0.5678 Remote Similarity NPC14537
0.5678 Remote Similarity NPC44514
0.5676 Remote Similarity NPC472264
0.5669 Remote Similarity NPC230849
0.5667 Remote Similarity NPC475150
0.5656 Remote Similarity NPC474411
0.5656 Remote Similarity NPC474431
0.5656 Remote Similarity NPC474459
0.5648 Remote Similarity NPC476141
0.5648 Remote Similarity NPC472136
0.5648 Remote Similarity NPC472161
0.5645 Remote Similarity NPC476814
0.5645 Remote Similarity NPC476813
0.5645 Remote Similarity NPC50694
0.5641 Remote Similarity NPC469598
0.5641 Remote Similarity NPC471258
0.5641 Remote Similarity NPC475149
0.5641 Remote Similarity NPC473289
0.5641 Remote Similarity NPC471097
0.5641 Remote Similarity NPC471083
0.5636 Remote Similarity NPC39290
0.5636 Remote Similarity NPC159369
0.5635 Remote Similarity NPC470276
0.5635 Remote Similarity NPC9714
0.5634 Remote Similarity NPC209509
0.5631 Remote Similarity NPC35574
0.563 Remote Similarity NPC93179
0.563 Remote Similarity NPC36497
0.563 Remote Similarity NPC473252
0.563 Remote Similarity NPC55462
0.5625 Remote Similarity NPC93027
0.5625 Remote Similarity NPC242692
0.562 Remote Similarity NPC473578
0.562 Remote Similarity NPC474725
0.5614 Remote Similarity NPC471257
0.5612 Remote Similarity NPC144511
0.5612 Remote Similarity NPC296522
0.5612 Remote Similarity NPC199557
0.5603 Remote Similarity NPC161069
0.5603 Remote Similarity NPC233932
0.5603 Remote Similarity NPC275686

  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 NPC476449 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
0.6952 Remote Similarity NPD5349 Clinical (unspecified phase)
0.6355 Remote Similarity NPD5781 Clinical (unspecified phase)
0.6239 Remote Similarity NPD6420 Discontinued
0.6179 Remote Similarity NPD2994 Approved
0.6168 Remote Similarity NPD790 Approved
0.6098 Remote Similarity NPD2115 Approved
0.6098 Remote Similarity NPD2116 Approved
0.6098 Remote Similarity NPD2117 Pre-registration
0.6032 Remote Similarity NPD2946 Phase 2
0.6 Remote Similarity NPD3031 Approved
0.6 Remote Similarity NPD3030 Approved
0.6 Remote Similarity NPD3032 Approved
0.5938 Remote Similarity NPD2694 Approved
0.5938 Remote Similarity NPD2697 Approved
0.5938 Remote Similarity NPD2695 Approved
0.5938 Remote Similarity NPD2696 Approved
0.5827 Remote Similarity NPD2838 Clinical (unspecified phase)
0.582 Remote Similarity NPD2607 Approved
0.5809 Remote Similarity NPD8643 Discontinued
0.5785 Remote Similarity NPD3643 Approved
0.5785 Remote Similarity NPD3642 Approved
0.5785 Remote Similarity NPD3644 Approved
0.5784 Remote Similarity NPD1402 Approved
0.5769 Remote Similarity NPD857 Phase 3
0.5739 Remote Similarity NPD6404 Discontinued
0.5736 Remote Similarity NPD2612 Approved
0.5736 Remote Similarity NPD3131 Approved
0.5736 Remote Similarity NPD4215 Approved
0.5736 Remote Similarity NPD4218 Approved
0.5736 Remote Similarity NPD2610 Approved
0.5736 Remote Similarity NPD2608 Approved
0.5736 Remote Similarity NPD2609 Approved
0.5736 Remote Similarity NPD2611 Approved
0.5736 Remote Similarity NPD4216 Approved
0.5736 Remote Similarity NPD4217 Approved
0.5736 Remote Similarity NPD3132 Approved
0.5735 Remote Similarity NPD8416 Discontinued
0.5692 Remote Similarity NPD2584 Suspended
0.568 Remote Similarity NPD6936 Clinical (unspecified phase)
0.568 Remote Similarity NPD6935 Phase 3
0.5676 Remote Similarity NPD6699 Clinical (unspecified phase)
0.5645 Remote Similarity NPD1371 Approved
0.5645 Remote Similarity NPD1370 Approved
0.5645 Remote Similarity NPD1373 Approved
0.5645 Remote Similarity NPD1374 Approved
0.5635 Remote Similarity NPD6918 Phase 1
0.5625 Remote Similarity NPD4504 Clinical (unspecified phase)
0.5625 Remote Similarity NPD7739 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