NPASS Compound

Structure

NPC473588 OpenBabel07101718312D 23 23 0 0 1 0 0 0 0 0999 V2000 -13.8564 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -13.8564 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.9904 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.1244 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.2583 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3923 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5263 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6603 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 1.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 6 2 0 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 8 9 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 16 18 1 0 0 0 0 16 20 1 0 0 0 0 17 19 1 0 0 0 0 17 22 1 0 0 0 0 18 15 1 1 0 0 0 18 22 1 0 0 0 0 19 20 1 0 0 0 0 19 21 1 6 0 0 0 20 23 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	318.27
Volume:	366.158
LogP:	0.925
LogD:	2.222
LogS:	-2.069
# Rotatable Bonds:	10
TPSA:	58.28
# H-Bond Aceptor:	3
# H-Bond Donor:	4
# Rings:	1
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.426
Synthetic Accessibility Score:	4.5
Fsp3:	0.6
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:	-5.148
MDCK Permeability:	2.888347808038816e-05
Pgp-inhibitor:	0.064
Pgp-substrate:	0.015
Human Intestinal Absorption (HIA):	0.042
20% Bioavailability (F20%):	0.669
30% Bioavailability (F30%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.049
Plasma Protein Binding (PPB):	71.36736297607422%
Volume Distribution (VD):	0.687
Pgp-substrate:	21.76215934753418%

ADMET: Metabolism

CYP1A2-inhibitor:	0.1
CYP1A2-substrate:	0.853
CYP2C19-inhibitor:	0.182
CYP2C19-substrate:	0.828
CYP2C9-inhibitor:	0.032
CYP2C9-substrate:	0.967
CYP2D6-inhibitor:	0.908
CYP2D6-substrate:	0.956
CYP3A4-inhibitor:	0.832
CYP3A4-substrate:	0.098

ADMET: Excretion

Clearance (CL):	2.312
Half-life (T1/2):	0.227

ADMET: Toxicity

hERG Blockers:	0.981
Human Hepatotoxicity (H-HT):	0.906
Drug-inuced Liver Injury (DILI):	0.451
AMES Toxicity:	0.135
Rat Oral Acute Toxicity:	0.661
Maximum Recommended Daily Dose:	0.929
Skin Sensitization:	0.955
Carcinogencity:	0.208
Eye Corrosion:	0.719
Eye Irritation:	0.045
Respiratory Toxicity:	0.903

Download Data

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

Natural Product: NPC473588

Natural Product ID:	NPC473588
*Common Name:**	Pseudodistomin F
IUPAC Name:	(2S,4R,5S)-5-amino-2-[(1E,3E,8E,10E)-pentadeca-1,3,8,10-tetraenyl]piperidin-4-ol
Synonyms:	Pseudodistomin F
Standard InCHIKey:	OFSZNJWXVVKUPZ-QVYNGYPTSA-N
Standard InCHI:	InChI=1S/C20H34N2O/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18-16-20(23)19(21)17-22-18/h5-8,12-15,18-20,22-23H,2-4,9-11,16-17,21H2,1H3/b6-5+,8-7+,13-12+,15-14+/t18-,19+,20-/m1/s1
SMILES:	CCCC/C=C/C=C/CCC/C=C/C=C/[C@H]1NC[C@@H]([C@@H](C1)O)N
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL446568
PubChem CID:	10710717
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines [CHEMONTID:0002357] Aminopiperidines

*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
NPO28004	Pseudodistoma megalarva	Species	Pseudodistomidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9358640]
NPO28004	Pseudodistoma megalarva	Species	Pseudodistomidae	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

Activity Type	# Activity
Others	4

Activity Type	# Activity
Organism	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	Activity	=	3.1	ug	PMID[461255]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	Activity	=	9.0	ug	PMID[461255]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	Activity	=	20.0	ug	PMID[461255]
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	Activity	=	3.3	ug	PMID[461255]

☑ 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 NPC473588 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	52
0.1-0.2	3999
0.2-0.3	25629
0.3-0.4	10910
0.4-0.5	1828
0.5-0.6	237
0.6-0.7	32
0.7-0.8	3
0.8-0.85	1
0.85-0.9	1
0.9-0.95	3
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC78562
0.9178	High Similarity	NPC475363
0.9178	High Similarity	NPC473972
0.9178	High Similarity	NPC473971
0.875	High Similarity	NPC26932
0.7945	Intermediate Similarity	NPC23721
0.7436	Intermediate Similarity	NPC470993
0.7436	Intermediate Similarity	NPC470992
0.72	Intermediate Similarity	NPC113224
0.6892	Remote Similarity	NPC47333
0.68	Remote Similarity	NPC55068
0.6596	Remote Similarity	NPC25033
0.6596	Remote Similarity	NPC119225
0.6596	Remote Similarity	NPC476261
0.6596	Remote Similarity	NPC471635
0.6596	Remote Similarity	NPC470382
0.6585	Remote Similarity	NPC470994
0.6579	Remote Similarity	NPC477106
0.6575	Remote Similarity	NPC302569
0.6575	Remote Similarity	NPC168308
0.6512	Remote Similarity	NPC209232
0.6506	Remote Similarity	NPC3094
0.6506	Remote Similarity	NPC51055
0.6506	Remote Similarity	NPC212008
0.6506	Remote Similarity	NPC140327
0.6506	Remote Similarity	NPC62293
0.6322	Remote Similarity	NPC476560
0.631	Remote Similarity	NPC34672
0.6279	Remote Similarity	NPC473695
0.6279	Remote Similarity	NPC473446
0.622	Remote Similarity	NPC324638
0.6139	Remote Similarity	NPC55336
0.6136	Remote Similarity	NPC207657
0.6136	Remote Similarity	NPC79367
0.6133	Remote Similarity	NPC204709
0.6044	Remote Similarity	NPC475975
0.6024	Remote Similarity	NPC476694
0.6024	Remote Similarity	NPC476696
0.6024	Remote Similarity	NPC476695
0.6	Remote Similarity	NPC135799
0.5962	Remote Similarity	NPC315426
0.596	Remote Similarity	NPC474164
0.5941	Remote Similarity	NPC118275
0.593	Remote Similarity	NPC217095
0.593	Remote Similarity	NPC264417
0.5922	Remote Similarity	NPC477000
0.5922	Remote Similarity	NPC477001
0.5905	Remote Similarity	NPC159367
0.5897	Remote Similarity	NPC470738
0.5897	Remote Similarity	NPC42477
0.5875	Remote Similarity	NPC206660
0.5867	Remote Similarity	NPC242930
0.5844	Remote Similarity	NPC143809
0.5844	Remote Similarity	NPC290106
0.5844	Remote Similarity	NPC193593
0.5844	Remote Similarity	NPC76726
0.5843	Remote Similarity	NPC157173
0.5833	Remote Similarity	NPC97614
0.5833	Remote Similarity	NPC306973
0.5802	Remote Similarity	NPC477525
0.5783	Remote Similarity	NPC268922
0.575	Remote Similarity	NPC471023
0.5743	Remote Similarity	NPC315170
0.5732	Remote Similarity	NPC315141
0.5732	Remote Similarity	NPC129995
0.5728	Remote Similarity	NPC471258
0.5728	Remote Similarity	NPC176012
0.5714	Remote Similarity	NPC291196
0.5714	Remote Similarity	NPC103712
0.5698	Remote Similarity	NPC314678
0.5676	Remote Similarity	NPC474322
0.5673	Remote Similarity	NPC473254
0.5663	Remote Similarity	NPC471418
0.5641	Remote Similarity	NPC321030
0.5625	Remote Similarity	NPC306462
0.5625	Remote Similarity	NPC150680
0.5625	Remote Similarity	NPC2432
0.5625	Remote Similarity	NPC22774
0.5625	Remote Similarity	NPC69669
0.5625	Remote Similarity	NPC218150
0.5625	Remote Similarity	NPC101139
0.561	Remote Similarity	NPC286851
0.561	Remote Similarity	NPC303798
0.56	Remote Similarity	NPC469739

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 NPC473588 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	63
0.1-0.2	362
0.2-0.3	4674
0.3-0.4	3347
0.4-0.5	660
0.5-0.6	43
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.68	Remote Similarity	NPD3210	Clinical (unspecified phase)
0.622	Remote Similarity	NPD3212	Clinical (unspecified phase)
0.5857	Remote Similarity	NPD399	Approved
0.5857	Remote Similarity	NPD400	Approved
0.5857	Remote Similarity	NPD398	Approved
0.5765	Remote Similarity	NPD5365	Phase 2
0.5625	Remote Similarity	NPD9026	Phase 2
0.5625	Remote Similarity	NPD9029	Phase 3
0.5625	Remote Similarity	NPD9027	Phase 3
0.5625	Remote Similarity	NPD9028	Phase 2
0.5616	Remote Similarity	NPD3214	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