Structure

Physi-Chem Properties

Molecular Weight:  261.16
Volume:  253.943
LogP:  -1.46
LogD:  -1.361
LogS:  -0.056
# Rotatable Bonds:  4
TPSA:  104.39
# H-Bond Aceptor:  6
# H-Bond Donor:  5
# Rings:  2
# Heavy Atoms:  6

MedChem Properties

QED Drug-Likeness Score:  0.403
Synthetic Accessibility Score:  4.786
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:  -5.333
MDCK Permeability:  0.00022726900351699442
Pgp-inhibitor:  0.001
Pgp-substrate:  0.886
Human Intestinal Absorption (HIA):  0.957
20% Bioavailability (F20%):  0.028
30% Bioavailability (F30%):  0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.305
Plasma Protein Binding (PPB):  14.490403175354004%
Volume Distribution (VD):  0.42
Pgp-substrate:  71.40007781982422%

ADMET: Metabolism

CYP1A2-inhibitor:  0.024
CYP1A2-substrate:  0.044
CYP2C19-inhibitor:  0.013
CYP2C19-substrate:  0.059
CYP2C9-inhibitor:  0.001
CYP2C9-substrate:  0.384
CYP2D6-inhibitor:  0.009
CYP2D6-substrate:  0.313
CYP3A4-inhibitor:  0.001
CYP3A4-substrate:  0.033

ADMET: Excretion

Clearance (CL):  3.0
Half-life (T1/2):  0.626

ADMET: Toxicity

hERG Blockers:  0.018
Human Hepatotoxicity (H-HT):  0.55
Drug-inuced Liver Injury (DILI):  0.531
AMES Toxicity:  0.054
Rat Oral Acute Toxicity:  0.001
Maximum Recommended Daily Dose:  0.062
Skin Sensitization:  0.36
Carcinogencity:  0.019
Eye Corrosion:  0.006
Eye Irritation:  0.289
Respiratory Toxicity:  0.752

Download Data

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

  Natural Product: NPC475127

Natural Product ID:  NPC475127
Common Name*:   Alpha-5-C-(1,3-Dihydroxybutyl)Hyacinthacine A1
IUPAC Name:   (1S,2R,3R,5S,8R)-5-(1,3-dihydroxybutyl)-3-(hydroxymethyl)-2,3,5,6,7,8-hexahydro-1H-pyrrolizine-1,2-diol
Synonyms:  
Standard InCHIKey:  BWAQHMTWORTVIR-NTMPOCDESA-N
Standard InCHI:  InChI=1S/C12H23NO5/c1-6(15)4-10(16)7-2-3-8-11(17)12(18)9(5-14)13(7)8/h6-12,14-18H,2-5H2,1H3/t6?,7-,8+,9+,10?,11-,12+/m0/s1
SMILES:  CC(CC(C1CCC2N1C(C(C2O)O)CO)O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL498968
PubChem CID:   10355288
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 = 830000.0 nM PMID[496108]
NPT496 Individual Protein Alpha-L-fucosidase 1 Bos taurus Inhibition < 50.0 % PMID[496108]
NPT61 Individual Protein Beta-glucocerebrosidase Homo sapiens Inhibition < 50.0 % PMID[496108]
NPT1131 Individual Protein Alpha-galactosidase Coffea arabica Inhibition < 50.0 % PMID[496108]
NPT506 Individual Protein Beta-mannosidase Rattus norvegicus Inhibition < 50.0 % PMID[496108]
NPT2 Others Unspecified IC50 = 300000.0 nM PMID[496108]
NPT2 Others Unspecified IC50 = 3600.0 nM PMID[496108]
NPT671 Individual Protein Acidic alpha-glucosidase Rattus norvegicus IC50 = 350000.0 nM PMID[496108]
NPT2 Others Unspecified IC50 = 5100.0 nM PMID[496108]
NPT2 Others Unspecified IC50 = 9500.0 nM PMID[496108]
NPT2 Others Unspecified Inhibition < 50.0 % PMID[496108]
NPT2 Others Unspecified IC50 = 680000.0 nM PMID[496108]
NPT2 Others Unspecified IC50 = 180000.0 nM PMID[496108]

☑ 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 NPC475127 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
1.0 High Similarity NPC473419
1.0 High Similarity NPC475715
0.9841 High Similarity NPC474469
0.9841 High Similarity NPC266242
0.9841 High Similarity NPC306763
0.9841 High Similarity NPC254617
0.9841 High Similarity NPC74555
0.9683 High Similarity NPC141156
0.9683 High Similarity NPC184150
0.9683 High Similarity NPC59221
0.9538 High Similarity NPC163538
0.9538 High Similarity NPC115800
0.9524 High Similarity NPC294883
0.9524 High Similarity NPC12514
0.8485 Intermediate Similarity NPC233034
0.8382 Intermediate Similarity NPC34291
0.8382 Intermediate Similarity NPC126664
0.8143 Intermediate Similarity NPC473710
0.8143 Intermediate Similarity NPC475694
0.7941 Intermediate Similarity NPC474928
0.7937 Intermediate Similarity NPC275727
0.7937 Intermediate Similarity NPC471423
0.7937 Intermediate Similarity NPC471442
0.7794 Intermediate Similarity NPC471419
0.7794 Intermediate Similarity NPC163134
0.7692 Intermediate Similarity NPC471605
0.7692 Intermediate Similarity NPC471443
0.7671 Intermediate Similarity NPC474468
0.7606 Intermediate Similarity NPC171850
0.7571 Intermediate Similarity NPC101746
0.7571 Intermediate Similarity NPC116377
0.7571 Intermediate Similarity NPC77191
0.7571 Intermediate Similarity NPC69798
0.7571 Intermediate Similarity NPC473952
0.75 Intermediate Similarity NPC62507
0.75 Intermediate Similarity NPC8087
0.75 Intermediate Similarity NPC57846
0.75 Intermediate Similarity NPC30126
0.75 Intermediate Similarity NPC474014
0.7297 Intermediate Similarity NPC285014
0.7297 Intermediate Similarity NPC255535
0.7297 Intermediate Similarity NPC299603
0.7297 Intermediate Similarity NPC137554
0.7297 Intermediate Similarity NPC28959
0.726 Intermediate Similarity NPC268922
0.7206 Intermediate Similarity NPC471421
0.7206 Intermediate Similarity NPC233364
0.7206 Intermediate Similarity NPC170172
0.7164 Intermediate Similarity NPC293551
0.7143 Intermediate Similarity NPC52533
0.7123 Intermediate Similarity NPC471418
0.7067 Intermediate Similarity NPC476695
0.7067 Intermediate Similarity NPC476694
0.7067 Intermediate Similarity NPC476696
0.697 Remote Similarity NPC178263
0.697 Remote Similarity NPC277072
0.6912 Remote Similarity NPC65832
0.6912 Remote Similarity NPC311668
0.6912 Remote Similarity NPC10262
0.6849 Remote Similarity NPC286851
0.6849 Remote Similarity NPC303798
0.6712 Remote Similarity NPC198341
0.6712 Remote Similarity NPC75435
0.6712 Remote Similarity NPC471892
0.6712 Remote Similarity NPC471780
0.6712 Remote Similarity NPC223386
0.6712 Remote Similarity NPC142290
0.6667 Remote Similarity NPC145627
0.6667 Remote Similarity NPC8979
0.6622 Remote Similarity NPC315980
0.6548 Remote Similarity NPC165119
0.6543 Remote Similarity NPC233108
0.6522 Remote Similarity NPC313821
0.6479 Remote Similarity NPC76726
0.6479 Remote Similarity NPC193593
0.6479 Remote Similarity NPC290106
0.6479 Remote Similarity NPC143809
0.6471 Remote Similarity NPC272396
0.6463 Remote Similarity NPC150557
0.6438 Remote Similarity NPC2432
0.6438 Remote Similarity NPC150680
0.6438 Remote Similarity NPC17455
0.6438 Remote Similarity NPC22774
0.6438 Remote Similarity NPC69669
0.6438 Remote Similarity NPC306462
0.6438 Remote Similarity NPC218150
0.6338 Remote Similarity NPC204709
0.631 Remote Similarity NPC471420
0.6267 Remote Similarity NPC160661
0.625 Remote Similarity NPC315806
0.625 Remote Similarity NPC306838
0.6234 Remote Similarity NPC195165
0.6232 Remote Similarity NPC270041
0.619 Remote Similarity NPC100204
0.619 Remote Similarity NPC83248
0.6186 Remote Similarity NPC314387
0.6087 Remote Similarity NPC123814
0.6027 Remote Similarity NPC319991
0.6023 Remote Similarity NPC277918
0.6 Remote Similarity NPC471844
0.6 Remote Similarity NPC477200
0.597 Remote Similarity NPC29222
0.597 Remote Similarity NPC121062
0.597 Remote Similarity NPC96966
0.5955 Remote Similarity NPC469363
0.5946 Remote Similarity NPC328786
0.5946 Remote Similarity NPC474627
0.5946 Remote Similarity NPC201338
0.5875 Remote Similarity NPC327486
0.5875 Remote Similarity NPC223174
0.5875 Remote Similarity NPC327753
0.5867 Remote Similarity NPC112398
0.5862 Remote Similarity NPC36927
0.5862 Remote Similarity NPC271772
0.5857 Remote Similarity NPC474322
0.5854 Remote Similarity NPC126186
0.5833 Remote Similarity NPC329077
0.5802 Remote Similarity NPC306973
0.5761 Remote Similarity NPC322966
0.5733 Remote Similarity NPC319131
0.5732 Remote Similarity NPC29326
0.5714 Remote Similarity NPC470782
0.5714 Remote Similarity NPC217095
0.5714 Remote Similarity NPC264417
0.5698 Remote Similarity NPC98750
0.5694 Remote Similarity NPC471917
0.5682 Remote Similarity NPC81006
0.5641 Remote Similarity NPC472609
0.5632 Remote Similarity NPC90839
0.5632 Remote Similarity NPC216090
0.5632 Remote Similarity NPC70574
0.5625 Remote Similarity NPC316445
0.5618 Remote Similarity NPC93630

  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 NPC475127 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
0.9231 High Similarity NPD9444 Discontinued
0.8485 Intermediate Similarity NPD9440 Discontinued
0.8382 Intermediate Similarity NPD9443 Clinical (unspecified phase)
0.75 Intermediate Similarity NPD393 Approved
0.7375 Intermediate Similarity NPD883 Phase 2
0.7375 Intermediate Similarity NPD882 Phase 2
0.7353 Intermediate Similarity NPD9455 Approved
0.6857 Remote Similarity NPD9240 Approved
0.6857 Remote Similarity NPD9239 Approved
0.6522 Remote Similarity NPD3190 Approved
0.6522 Remote Similarity NPD3191 Approved
0.6522 Remote Similarity NPD3189 Approved
0.6438 Remote Similarity NPD9027 Phase 3
0.6438 Remote Similarity NPD9028 Phase 2
0.6438 Remote Similarity NPD9026 Phase 2
0.6438 Remote Similarity NPD9029 Phase 3
0.6267 Remote Similarity NPD1457 Discontinued
0.625 Remote Similarity NPD9653 Clinical (unspecified phase)
0.6186 Remote Similarity NPD3184 Approved
0.6186 Remote Similarity NPD3185 Approved
0.6186 Remote Similarity NPD3182 Approved
0.6186 Remote Similarity NPD3183 Approved
0.6136 Remote Similarity NPD394 Phase 3
0.6087 Remote Similarity NPD3215 Phase 1
0.6047 Remote Similarity NPD2691 Clinical (unspecified phase)
0.6024 Remote Similarity NPD372 Clinical (unspecified phase)
0.5875 Remote Similarity NPD9445 Approved
0.5867 Remote Similarity NPD9022 Phase 2
0.5867 Remote Similarity NPD9024 Phase 2
0.5843 Remote Similarity NPD9401 Discovery
0.5824 Remote Similarity NPD3177 Phase 3
0.5802 Remote Similarity NPD9446 Approved
0.5797 Remote Similarity NPD3214 Discontinued
0.5778 Remote Similarity NPD3723 Clinical (unspecified phase)
0.5769 Remote Similarity NPD3188 Approved
0.5732 Remote Similarity NPD3187 Discontinued
0.5714 Remote Similarity NPD9407 Approved
0.5679 Remote Similarity NPD2220 Clinical (unspecified phase)
0.5658 Remote Similarity NPD3193 Approved
0.5658 Remote Similarity NPD3192 Approved
0.5638 Remote Similarity NPD6943 Clinical (unspecified phase)
0.5604 Remote Similarity NPD619 Phase 3

  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