Structure

Physi-Chem Properties

Molecular Weight:  277.15
Volume:  262.733
LogP:  -2.07
LogD:  -1.726
LogS:  -0.115
# Rotatable Bonds:  5
TPSA:  124.62
# H-Bond Aceptor:  7
# H-Bond Donor:  6
# Rings:  2
# Heavy Atoms:  7

MedChem Properties

QED Drug-Likeness Score:  0.317
Synthetic Accessibility Score:  4.768
Fsp3:  1.0
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:  -5.526
MDCK Permeability:  0.00046001418377272785
Pgp-inhibitor:  0.0
Pgp-substrate:  0.802
Human Intestinal Absorption (HIA):  0.972
20% Bioavailability (F20%):  0.305
30% Bioavailability (F30%):  0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.312
Plasma Protein Binding (PPB):  12.943731307983398%
Volume Distribution (VD):  0.346
Pgp-substrate:  73.01170349121094%

ADMET: Metabolism

CYP1A2-inhibitor:  0.013
CYP1A2-substrate:  0.03
CYP2C19-inhibitor:  0.008
CYP2C19-substrate:  0.053
CYP2C9-inhibitor:  0.0
CYP2C9-substrate:  0.119
CYP2D6-inhibitor:  0.004
CYP2D6-substrate:  0.187
CYP3A4-inhibitor:  0.001
CYP3A4-substrate:  0.012

ADMET: Excretion

Clearance (CL):  2.077
Half-life (T1/2):  0.693

ADMET: Toxicity

hERG Blockers:  0.022
Human Hepatotoxicity (H-HT):  0.608
Drug-inuced Liver Injury (DILI):  0.598
AMES Toxicity:  0.067
Rat Oral Acute Toxicity:  0.001
Maximum Recommended Daily Dose:  0.067
Skin Sensitization:  0.431
Carcinogencity:  0.014
Eye Corrosion:  0.003
Eye Irritation:  0.091
Respiratory Toxicity:  0.518

Download Data

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

  Natural Product: NPC474469

Natural Product ID:  NPC474469
Common Name*:   Alpha-5-C-(1,3,4-Trihydroxybutyl)Hyacinthacine A1
IUPAC Name:   4-[(3S,5R,6R,7S,8R)-6,7-dihydroxy-5-(hydroxymethyl)-2,3,5,6,7,8-hexahydro-1H-pyrrolizin-3-yl]butane-1,2,4-triol
Synonyms:  
Standard InCHIKey:  HFTWYUZUQUCVPO-NTMPOCDESA-N
Standard InCHI:  InChI=1S/C12H23NO6/c14-4-6(16)3-10(17)7-1-2-8-11(18)12(19)9(5-15)13(7)8/h6-12,14-19H,1-5H2/t6?,7-,8+,9+,10?,11-,12+/m0/s1
SMILES:  OCC(CC([C@@H]1CC[C@H]2N1[C@H](CO)[C@H]([C@H]2O)O)O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL469437
PubChem CID:   11482798
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000220] Pyrrolizidines

*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
NPO22662 Scilla peruviana Species Hyacinthaceae Eukaryota n.a. n.a. n.a. PMID[15165148]
NPO22662 Scilla peruviana Species Hyacinthaceae 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
NPT509 Individual Protein Beta-galactosidase Bos taurus IC50 = 920000.0 nM PMID[522219]
NPT496 Individual Protein Alpha-L-fucosidase 1 Bos taurus Inhibition < 50.0 % PMID[522219]
NPT61 Individual Protein Beta-glucocerebrosidase Homo sapiens Inhibition < 50.0 % PMID[522219]
NPT1131 Individual Protein Alpha-galactosidase Coffea arabica Inhibition < 50.0 % PMID[522219]
NPT506 Individual Protein Beta-mannosidase Rattus norvegicus Inhibition < 50.0 % PMID[522219]
NPT2 Others Unspecified IC50 = 390000.0 nM PMID[522219]
NPT2 Others Unspecified IC50 = 650000.0 nM PMID[522219]
NPT2 Others Unspecified IC50 = 11400.0 nM PMID[522219]
NPT2 Others Unspecified IC50 = 25400.0 nM PMID[522219]
NPT2 Others Unspecified Inhibition < 50.0 % PMID[522219]
NPT671 Individual Protein Acidic alpha-glucosidase Rattus norvegicus Inhibition < 50.0 % PMID[522219]

☑ 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 NPC474469 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
0.9841 High Similarity NPC473419
0.9841 High Similarity NPC475715
0.9841 High Similarity NPC475127
0.9839 High Similarity NPC141156
0.9839 High Similarity NPC184150
0.9683 High Similarity NPC306763
0.9683 High Similarity NPC266242
0.9683 High Similarity NPC254617
0.9683 High Similarity NPC74555
0.9677 High Similarity NPC12514
0.9677 High Similarity NPC294883
0.9524 High Similarity NPC59221
0.9385 High Similarity NPC163538
0.9385 High Similarity NPC115800
0.8615 High Similarity NPC233034
0.8507 High Similarity NPC34291
0.8507 High Similarity NPC126664
0.8065 Intermediate Similarity NPC275727
0.8 Intermediate Similarity NPC473710
0.8 Intermediate Similarity NPC475694
0.7794 Intermediate Similarity NPC474928
0.7778 Intermediate Similarity NPC471442
0.7778 Intermediate Similarity NPC474468
0.7778 Intermediate Similarity NPC471423
0.7681 Intermediate Similarity NPC116377
0.7681 Intermediate Similarity NPC101746
0.7681 Intermediate Similarity NPC77191
0.7681 Intermediate Similarity NPC69798
0.7681 Intermediate Similarity NPC473952
0.7647 Intermediate Similarity NPC471419
0.7647 Intermediate Similarity NPC163134
0.7612 Intermediate Similarity NPC8087
0.7612 Intermediate Similarity NPC62507
0.7538 Intermediate Similarity NPC471443
0.7538 Intermediate Similarity NPC471605
0.7465 Intermediate Similarity NPC171850
0.7397 Intermediate Similarity NPC28959
0.7397 Intermediate Similarity NPC299603
0.7397 Intermediate Similarity NPC255535
0.7397 Intermediate Similarity NPC137554
0.7397 Intermediate Similarity NPC285014
0.7353 Intermediate Similarity NPC474014
0.7353 Intermediate Similarity NPC57846
0.7353 Intermediate Similarity NPC30126
0.7222 Intermediate Similarity NPC471418
0.7123 Intermediate Similarity NPC268922
0.7059 Intermediate Similarity NPC471421
0.7059 Intermediate Similarity NPC233364
0.7059 Intermediate Similarity NPC170172
0.7024 Intermediate Similarity NPC52533
0.7015 Intermediate Similarity NPC293551
0.7015 Intermediate Similarity NPC311668
0.7015 Intermediate Similarity NPC65832
0.7015 Intermediate Similarity NPC10262
0.6933 Remote Similarity NPC476696
0.6933 Remote Similarity NPC476695
0.6933 Remote Similarity NPC476694
0.6818 Remote Similarity NPC178263
0.6818 Remote Similarity NPC277072
0.6806 Remote Similarity NPC142290
0.6806 Remote Similarity NPC471892
0.6806 Remote Similarity NPC75435
0.6806 Remote Similarity NPC471780
0.6806 Remote Similarity NPC223386
0.6806 Remote Similarity NPC198341
0.6712 Remote Similarity NPC303798
0.6712 Remote Similarity NPC315980
0.6712 Remote Similarity NPC286851
0.6627 Remote Similarity NPC165119
0.6571 Remote Similarity NPC76726
0.6571 Remote Similarity NPC193593
0.6571 Remote Similarity NPC143809
0.6571 Remote Similarity NPC290106
0.6567 Remote Similarity NPC272396
0.6528 Remote Similarity NPC218150
0.6528 Remote Similarity NPC22774
0.6528 Remote Similarity NPC2432
0.6528 Remote Similarity NPC145627
0.6528 Remote Similarity NPC150680
0.6528 Remote Similarity NPC306462
0.6528 Remote Similarity NPC69669
0.6522 Remote Similarity NPC8979
0.642 Remote Similarity NPC233108
0.6413 Remote Similarity NPC313821
0.6341 Remote Similarity NPC150557
0.6329 Remote Similarity NPC315806
0.6322 Remote Similarity NPC306838
0.6301 Remote Similarity NPC17455
0.6265 Remote Similarity NPC100204
0.6265 Remote Similarity NPC83248
0.6197 Remote Similarity NPC204709
0.619 Remote Similarity NPC471420
0.6133 Remote Similarity NPC160661
0.6104 Remote Similarity NPC195165
0.6087 Remote Similarity NPC270041
0.6082 Remote Similarity NPC314387
0.6023 Remote Similarity NPC469363
0.5946 Remote Similarity NPC112398
0.5942 Remote Similarity NPC123814
0.593 Remote Similarity NPC271772
0.593 Remote Similarity NPC36927
0.5909 Remote Similarity NPC277918
0.5904 Remote Similarity NPC329077
0.59 Remote Similarity NPC471844
0.589 Remote Similarity NPC319991
0.5875 Remote Similarity NPC477200
0.5821 Remote Similarity NPC96966
0.5821 Remote Similarity NPC121062
0.5821 Remote Similarity NPC29222
0.5811 Remote Similarity NPC328786
0.5811 Remote Similarity NPC474627
0.5811 Remote Similarity NPC201338
0.5802 Remote Similarity NPC29326
0.5783 Remote Similarity NPC470782
0.5765 Remote Similarity NPC98750
0.575 Remote Similarity NPC327753
0.575 Remote Similarity NPC327486
0.575 Remote Similarity NPC223174
0.5747 Remote Similarity NPC81006
0.5732 Remote Similarity NPC126186
0.5714 Remote Similarity NPC474322
0.5698 Remote Similarity NPC70574
0.5698 Remote Similarity NPC90839
0.5696 Remote Similarity NPC316445
0.5679 Remote Similarity NPC306973
0.5652 Remote Similarity NPC275715
0.5652 Remote Similarity NPC322966
0.56 Remote Similarity NPC319131

  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 NPC474469 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
0.9375 High Similarity NPD9444 Discontinued
0.8615 High Similarity NPD9440 Discontinued
0.8507 High Similarity NPD9443 Clinical (unspecified phase)
0.7463 Intermediate Similarity NPD9455 Approved
0.7353 Intermediate Similarity NPD393 Approved
0.725 Intermediate Similarity NPD883 Phase 2
0.725 Intermediate Similarity NPD882 Phase 2
0.6714 Remote Similarity NPD9239 Approved
0.6714 Remote Similarity NPD9240 Approved
0.6528 Remote Similarity NPD9026 Phase 2
0.6528 Remote Similarity NPD9028 Phase 2
0.6528 Remote Similarity NPD9027 Phase 3
0.6528 Remote Similarity NPD9029 Phase 3
0.6413 Remote Similarity NPD3191 Approved
0.6413 Remote Similarity NPD3189 Approved
0.6413 Remote Similarity NPD3190 Approved
0.6329 Remote Similarity NPD9653 Clinical (unspecified phase)
0.6207 Remote Similarity NPD394 Phase 3
0.6133 Remote Similarity NPD1457 Discontinued
0.6098 Remote Similarity NPD372 Clinical (unspecified phase)
0.6082 Remote Similarity NPD3185 Approved
0.6082 Remote Similarity NPD3183 Approved
0.6082 Remote Similarity NPD3184 Approved
0.6082 Remote Similarity NPD3182 Approved
0.5946 Remote Similarity NPD9022 Phase 2
0.5946 Remote Similarity NPD9024 Phase 2
0.5942 Remote Similarity NPD3215 Phase 1
0.593 Remote Similarity NPD2691 Clinical (unspecified phase)
0.5909 Remote Similarity NPD9401 Discovery
0.5783 Remote Similarity NPD9407 Approved
0.575 Remote Similarity NPD2220 Clinical (unspecified phase)
0.575 Remote Similarity NPD9445 Approved
0.5733 Remote Similarity NPD3193 Approved
0.5733 Remote Similarity NPD3192 Approved
0.5714 Remote Similarity NPD3177 Phase 3
0.5679 Remote Similarity NPD9446 Approved
0.5673 Remote Similarity NPD3188 Approved
0.5667 Remote Similarity NPD3723 Clinical (unspecified phase)
0.5652 Remote Similarity NPD3214 Discontinued
0.561 Remote Similarity NPD3187 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