Structure

Physi-Chem Properties

Molecular Weight:  423.26
Volume:  418.763
LogP:  1.292
LogD:  1.165
LogS:  -3.561
# Rotatable Bonds:  4
TPSA:  91.62
# H-Bond Aceptor:  7
# H-Bond Donor:  3
# Rings:  6
# Heavy Atoms:  7

MedChem Properties

QED Drug-Likeness Score:  0.603
Synthetic Accessibility Score:  7.248
Fsp3:  1.0
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.112
MDCK Permeability:  6.951967952772975e-05
Pgp-inhibitor:  0.401
Pgp-substrate:  0.998
Human Intestinal Absorption (HIA):  0.328
20% Bioavailability (F20%):  0.013
30% Bioavailability (F30%):  0.623

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.143
Plasma Protein Binding (PPB):  17.036415100097656%
Volume Distribution (VD):  0.746
Pgp-substrate:  67.14989471435547%

ADMET: Metabolism

CYP1A2-inhibitor:  0.004
CYP1A2-substrate:  0.896
CYP2C19-inhibitor:  0.004
CYP2C19-substrate:  0.593
CYP2C9-inhibitor:  0.001
CYP2C9-substrate:  0.006
CYP2D6-inhibitor:  0.003
CYP2D6-substrate:  0.264
CYP3A4-inhibitor:  0.02
CYP3A4-substrate:  0.398

ADMET: Excretion

Clearance (CL):  4.745
Half-life (T1/2):  0.358

ADMET: Toxicity

hERG Blockers:  0.083
Human Hepatotoxicity (H-HT):  0.448
Drug-inuced Liver Injury (DILI):  0.031
AMES Toxicity:  0.035
Rat Oral Acute Toxicity:  0.338
Maximum Recommended Daily Dose:  0.245
Skin Sensitization:  0.815
Carcinogencity:  0.6
Eye Corrosion:  0.022
Eye Irritation:  0.015
Respiratory Toxicity:  0.984

Download Data

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

  Natural Product: NPC475887

Natural Product ID:  NPC475887
Common Name*:   Lappaconine
IUPAC Name:   n.a.
Synonyms:   Lappaconine
Standard InCHIKey:  ZBSZKFYYJKXUHF-QWRRKDOKSA-N
Standard InCHI:  InChI=1S/C23H37NO6/c1-5-24-11-20(25)7-6-17(29-3)22-15(20)9-13(18(22)24)21(26)10-14(28-2)12-8-16(22)23(21,27)19(12)30-4/h12-19,25-27H,5-11H2,1-4H3/t12-,13-,14+,15-,16+,17+,18-,19+,20-,21+,22+,23+/m1/s1
SMILES:  CCN1CC2(CCC(C34C2CC(C31)C5(CC(C6CC4C5(C6OC)O)OC)O)OC)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL517953
PubChem CID:   44566468
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0003789] Lappaconitine-type diterpenoid alkaloids

*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
NPO33014 delphinium cashmirianum Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[541686]

☑ 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
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus Activity = -5.0 bpm PMID[549722]
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus Activity = 0.0 bpm PMID[549722]

☑ 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 NPC475887 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
0.9464 High Similarity NPC99905
0.9464 High Similarity NPC208118
0.9464 High Similarity NPC96080
0.9 High Similarity NPC139778
0.8983 High Similarity NPC476501
0.8908 High Similarity NPC476497
0.8899 High Similarity NPC8009
0.8899 High Similarity NPC48127
0.8899 High Similarity NPC267217
0.8899 High Similarity NPC83047
0.8833 High Similarity NPC476967
0.8413 Intermediate Similarity NPC474210
0.8291 Intermediate Similarity NPC476502
0.7656 Intermediate Similarity NPC309249
0.7308 Intermediate Similarity NPC212106
0.7131 Intermediate Similarity NPC287764
0.704 Intermediate Similarity NPC476499
0.7031 Intermediate Similarity NPC470594
0.7031 Intermediate Similarity NPC470593
0.6977 Remote Similarity NPC476504
0.6947 Remote Similarity NPC476503
0.688 Remote Similarity NPC476498
0.6789 Remote Similarity NPC109533
0.6715 Remote Similarity NPC262050
0.6612 Remote Similarity NPC475518
0.661 Remote Similarity NPC155985
0.6589 Remote Similarity NPC476955
0.6562 Remote Similarity NPC28224
0.6555 Remote Similarity NPC289140
0.6529 Remote Similarity NPC201712
0.6514 Remote Similarity NPC18857
0.6514 Remote Similarity NPC67657
0.6491 Remote Similarity NPC471240
0.648 Remote Similarity NPC46981
0.648 Remote Similarity NPC317534
0.6446 Remote Similarity NPC475249
0.6446 Remote Similarity NPC220111
0.6441 Remote Similarity NPC277774
0.6422 Remote Similarity NPC105208
0.6422 Remote Similarity NPC128951
0.6422 Remote Similarity NPC477227
0.6422 Remote Similarity NPC302578
0.6422 Remote Similarity NPC185915
0.6422 Remote Similarity NPC192046
0.6387 Remote Similarity NPC3538
0.6387 Remote Similarity NPC113500
0.6387 Remote Similarity NPC477224
0.6372 Remote Similarity NPC478054
0.6364 Remote Similarity NPC473537
0.6356 Remote Similarity NPC36372
0.6356 Remote Similarity NPC293609
0.6349 Remote Similarity NPC478053
0.6343 Remote Similarity NPC238323
0.6333 Remote Similarity NPC92196
0.633 Remote Similarity NPC163597
0.6325 Remote Similarity NPC228059
0.6324 Remote Similarity NPC75839
0.6324 Remote Similarity NPC68327
0.6316 Remote Similarity NPC320824
0.6311 Remote Similarity NPC252564
0.6306 Remote Similarity NPC477282
0.6306 Remote Similarity NPC287452
0.6306 Remote Similarity NPC81074
0.6306 Remote Similarity NPC269333
0.6303 Remote Similarity NPC167644
0.6303 Remote Similarity NPC311246
0.6296 Remote Similarity NPC478138
0.6296 Remote Similarity NPC139857
0.6288 Remote Similarity NPC39485
0.6288 Remote Similarity NPC221196
0.6283 Remote Similarity NPC475388
0.6281 Remote Similarity NPC473287
0.6271 Remote Similarity NPC279329
0.6271 Remote Similarity NPC312637
0.6271 Remote Similarity NPC223143
0.6261 Remote Similarity NPC266651
0.6261 Remote Similarity NPC273290
0.6261 Remote Similarity NPC232044
0.625 Remote Similarity NPC16449
0.625 Remote Similarity NPC309866
0.6239 Remote Similarity NPC128475
0.6239 Remote Similarity NPC196136
0.6239 Remote Similarity NPC158208
0.6239 Remote Similarity NPC243027
0.6239 Remote Similarity NPC317242
0.623 Remote Similarity NPC477222
0.623 Remote Similarity NPC477223
0.6218 Remote Similarity NPC5632
0.6218 Remote Similarity NPC59006
0.6218 Remote Similarity NPC149966
0.6216 Remote Similarity NPC147993
0.6207 Remote Similarity NPC131365
0.6198 Remote Similarity NPC473067
0.6198 Remote Similarity NPC473065
0.6198 Remote Similarity NPC473064
0.619 Remote Similarity NPC212874
0.6186 Remote Similarity NPC102725
0.6186 Remote Similarity NPC473472
0.6183 Remote Similarity NPC478137
0.6179 Remote Similarity NPC473638
0.6174 Remote Similarity NPC227260
0.6159 Remote Similarity NPC48886
0.6159 Remote Similarity NPC265275
0.6159 Remote Similarity NPC94881
0.6154 Remote Similarity NPC21035
0.6154 Remote Similarity NPC161928
0.6154 Remote Similarity NPC472396
0.6154 Remote Similarity NPC210658
0.6154 Remote Similarity NPC5943
0.6148 Remote Similarity NPC156377
0.6147 Remote Similarity NPC48795
0.6147 Remote Similarity NPC10476
0.6147 Remote Similarity NPC228994
0.6147 Remote Similarity NPC192501
0.6147 Remote Similarity NPC304499
0.6134 Remote Similarity NPC473542
0.6126 Remote Similarity NPC64081
0.6126 Remote Similarity NPC11907
0.6126 Remote Similarity NPC133596
0.6126 Remote Similarity NPC474574
0.6121 Remote Similarity NPC290612
0.6116 Remote Similarity NPC473503
0.6116 Remote Similarity NPC30687
0.6116 Remote Similarity NPC24960
0.6116 Remote Similarity NPC473774
0.6116 Remote Similarity NPC175
0.6116 Remote Similarity NPC45959
0.6116 Remote Similarity NPC475325
0.6116 Remote Similarity NPC252253
0.6115 Remote Similarity NPC280903
0.6115 Remote Similarity NPC470537
0.6111 Remote Similarity NPC241879
0.6105 Remote Similarity NPC40539
0.6102 Remote Similarity NPC281004
0.6098 Remote Similarity NPC233649
0.6098 Remote Similarity NPC292819
0.6098 Remote Similarity NPC470028
0.609 Remote Similarity NPC165396
0.6087 Remote Similarity NPC296686
0.6083 Remote Similarity NPC473830
0.6083 Remote Similarity NPC473066
0.6083 Remote Similarity NPC204881
0.608 Remote Similarity NPC477225
0.6069 Remote Similarity NPC108276
0.6069 Remote Similarity NPC163578
0.6068 Remote Similarity NPC155531
0.6068 Remote Similarity NPC215968
0.6068 Remote Similarity NPC477283
0.6066 Remote Similarity NPC469710
0.6066 Remote Similarity NPC477494
0.6066 Remote Similarity NPC474399
0.6055 Remote Similarity NPC470610
0.6055 Remote Similarity NPC153719
0.605 Remote Similarity NPC82955
0.605 Remote Similarity NPC20822
0.605 Remote Similarity NPC323156
0.6047 Remote Similarity NPC470595
0.6034 Remote Similarity NPC124690
0.6034 Remote Similarity NPC166521
0.6034 Remote Similarity NPC184195
0.6034 Remote Similarity NPC172769
0.6034 Remote Similarity NPC281470
0.6034 Remote Similarity NPC205
0.6033 Remote Similarity NPC476669
0.6033 Remote Similarity NPC211845
0.6033 Remote Similarity NPC149400
0.6033 Remote Similarity NPC182740
0.6033 Remote Similarity NPC122083
0.6033 Remote Similarity NPC88962
0.6033 Remote Similarity NPC256104
0.6033 Remote Similarity NPC144790
0.6032 Remote Similarity NPC68630
0.6032 Remote Similarity NPC52585
0.6032 Remote Similarity NPC228049
0.6031 Remote Similarity NPC246399
0.6031 Remote Similarity NPC34977
0.6017 Remote Similarity NPC43912
0.6017 Remote Similarity NPC140446
0.6016 Remote Similarity NPC304011
0.6016 Remote Similarity NPC142264
0.6016 Remote Similarity NPC139271
0.6016 Remote Similarity NPC476510
0.6016 Remote Similarity NPC121453
0.6 Remote Similarity NPC296734
0.6 Remote Similarity NPC154043
0.6 Remote Similarity NPC202688
0.6 Remote Similarity NPC470611
0.6 Remote Similarity NPC297058
0.6 Remote Similarity NPC60018
0.6 Remote Similarity NPC65550
0.6 Remote Similarity NPC475458
0.5986 Remote Similarity NPC478139
0.5984 Remote Similarity NPC253268
0.5984 Remote Similarity NPC174024
0.5984 Remote Similarity NPC473851
0.5984 Remote Similarity NPC131693
0.5984 Remote Similarity NPC312678
0.5984 Remote Similarity NPC294686
0.5984 Remote Similarity NPC179859
0.5984 Remote Similarity NPC475436

  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 NPC475887 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
0.6897 Remote Similarity NPD7991 Discontinued
0.6885 Remote Similarity NPD7646 Clinical (unspecified phase)
0.6694 Remote Similarity NPD8174 Phase 2
0.6639 Remote Similarity NPD7987 Approved
0.6639 Remote Similarity NPD7986 Approved
0.6639 Remote Similarity NPD7911 Approved
0.6639 Remote Similarity NPD7912 Approved
0.6589 Remote Similarity NPD7754 Approved
0.6589 Remote Similarity NPD7755 Approved
0.6532 Remote Similarity NPD6920 Discontinued
0.6532 Remote Similarity NPD8040 Discontinued
0.648 Remote Similarity NPD7989 Approved
0.648 Remote Similarity NPD7990 Approved
0.6364 Remote Similarity NPD7919 Phase 3
0.6364 Remote Similarity NPD7920 Phase 3
0.6311 Remote Similarity NPD8088 Phase 1
0.6261 Remote Similarity NPD394 Phase 3
0.6231 Remote Similarity NPD8077 Approved
0.6231 Remote Similarity NPD8078 Approved
0.6212 Remote Similarity NPD6940 Discontinued
0.6204 Remote Similarity NPD577 Phase 3
0.6204 Remote Similarity NPD591 Approved
0.6172 Remote Similarity NPD6415 Discontinued
0.6068 Remote Similarity NPD8308 Discontinued
0.6 Remote Similarity NPD8418 Phase 2
0.594 Remote Similarity NPD8298 Phase 2
0.5903 Remote Similarity NPD8449 Approved
0.5902 Remote Similarity NPD8171 Discontinued
0.5862 Remote Similarity NPD8450 Suspended
0.5826 Remote Similarity NPD6928 Phase 2
0.578 Remote Similarity NPD4267 Clinical (unspecified phase)
0.5652 Remote Similarity NPD7497 Discontinued
0.5625 Remote Similarity NPD4838 Approved
0.5625 Remote Similarity NPD4835 Approved
0.5625 Remote Similarity NPD4836 Approved
0.5625 Remote Similarity NPD4837 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