NPASS Compound

Structure

CID34672 OpenBabel06191715362D 30 30 0 0 0 0 0 0 0 0999 V2000 1.7321 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 6.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 6.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 5.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 6.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 6.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 6.5000 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 -5.1962 6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -0.0000 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 -6.0622 6.5000 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 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 6.0000 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 0.0000 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 6.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 1 3 1 0 0 0 0 2 4 1 0 0 0 0 3 5 1 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 8 10 1 0 0 0 0 9 11 1 0 0 0 0 10 12 1 0 0 0 0 11 13 1 0 0 0 0 12 14 1 0 0 0 0 13 15 1 0 0 0 0 14 16 2 0 0 0 0 15 17 1 0 0 0 0 16 19 1 0 0 0 0 17 22 1 0 0 0 0 18 20 1 0 0 0 0 18 21 1 0 0 0 0 19 23 2 0 0 0 0 20 24 1 0 0 0 0 21 25 1 0 0 0 0 22 26 1 0 0 0 0 23 27 1 0 0 0 0 24 28 1 0 0 0 0 25 28 1 0 0 0 0 26 29 1 0 0 0 0 27 28 1 0 0 0 0 27 30 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	419.38
Volume:	487.659
LogP:	8.411
LogD:	3.952
LogS:	-6.659
# Rotatable Bonds:	20
TPSA:	40.54
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	1
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.135
Synthetic Accessibility Score:	2.462
Fsp3:	0.815
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.132
MDCK Permeability:	1.348006753687514e-05
Pgp-inhibitor:	0.002
Pgp-substrate:	0.005
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.685
30% Bioavailability (F30%):	0.95

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.057
Plasma Protein Binding (PPB):	97.95819854736328%
Volume Distribution (VD):	1.324
Pgp-substrate:	1.4550368785858154%

ADMET: Metabolism

CYP1A2-inhibitor:	0.137
CYP1A2-substrate:	0.191
CYP2C19-inhibitor:	0.189
CYP2C19-substrate:	0.059
CYP2C9-inhibitor:	0.09
CYP2C9-substrate:	0.897
CYP2D6-inhibitor:	0.201
CYP2D6-substrate:	0.098
CYP3A4-inhibitor:	0.544
CYP3A4-substrate:	0.05

ADMET: Excretion

Clearance (CL):	3.655
Half-life (T1/2):	0.124

ADMET: Toxicity

hERG Blockers:	0.501
Human Hepatotoxicity (H-HT):	0.429
Drug-inuced Liver Injury (DILI):	0.026
AMES Toxicity:	0.008
Rat Oral Acute Toxicity:	0.053
Maximum Recommended Daily Dose:	0.269
Skin Sensitization:	0.99
Carcinogencity:	0.111
Eye Corrosion:	0.97
Eye Irritation:	0.873
Respiratory Toxicity:	0.968

Download Data

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

Natural Product: NPC34672

Natural Product ID:	NPC34672
*Common Name:**	Haloxyline A
IUPAC Name:	(2Z,4Z)-22-hydroxy-1-piperidin-1-yldocosa-2,4-dien-1-one
Synonyms:
Standard InCHIKey:	PRNFXRJMEAUSFT-QBTJJOFXSA-N
Standard InCHI:	InChI=1S/C27H49NO2/c29-26-22-17-15-13-11-9-7-5-3-1-2-4-6-8-10-12-14-16-19-23-27(30)28-24-20-18-21-25-28/h14,16,19,23,29H,1-13,15,17-18,20-22,24-26H2/b16-14-,23-19-
SMILES:	OCCCCCCCCCCCCCCCCC/C=CC=C/C(=O)N1CCCCC1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1169743
PubChem CID:	11362138
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines [CHEMONTID:0000335] N-acylpiperidines

*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
NPO20954	Haloxylon salicornicum	Species	Chenopodiaceae	Eukaryota	whole plant	Cholistan desert near district Bahawalpur (Punjab), Pakistan	2003-Oct	PMID[20542692]
NPO20954	Haloxylon salicornicum	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20954	Haloxylon salicornicum	Species	Chenopodiaceae	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
MIC	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	100.0	ug.mL-1	PMID[478438]

☑ 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 NPC34672 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	66
0.1-0.2	461
0.2-0.3	19122
0.3-0.4	17321
0.4-0.5	5212
0.5-0.6	471
0.6-0.7	34
0.7-0.8	7
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9324	High Similarity	NPC209232
0.8286	Intermediate Similarity	NPC206660
0.7857	Intermediate Similarity	NPC42477
0.726	Intermediate Similarity	NPC252684
0.7143	Intermediate Similarity	NPC226982
0.7143	Intermediate Similarity	NPC23721
0.7143	Intermediate Similarity	NPC277341
0.7093	Intermediate Similarity	NPC475975
0.6986	Remote Similarity	NPC133923
0.6962	Remote Similarity	NPC97614
0.6915	Remote Similarity	NPC91036
0.6914	Remote Similarity	NPC470993
0.6914	Remote Similarity	NPC470992
0.6849	Remote Similarity	NPC385
0.6786	Remote Similarity	NPC473972
0.6786	Remote Similarity	NPC473971
0.6786	Remote Similarity	NPC475363
0.6701	Remote Similarity	NPC100810
0.6701	Remote Similarity	NPC144714
0.6585	Remote Similarity	NPC26932
0.6559	Remote Similarity	NPC145707
0.6506	Remote Similarity	NPC470994
0.6471	Remote Similarity	NPC46268
0.6452	Remote Similarity	NPC17143
0.6452	Remote Similarity	NPC47230
0.6436	Remote Similarity	NPC472856
0.6429	Remote Similarity	NPC316730
0.6364	Remote Similarity	NPC77703
0.6322	Remote Similarity	NPC471768
0.6316	Remote Similarity	NPC329003
0.6316	Remote Similarity	NPC326524
0.6316	Remote Similarity	NPC325550
0.631	Remote Similarity	NPC78562
0.631	Remote Similarity	NPC473588
0.6279	Remote Similarity	NPC244256
0.6279	Remote Similarity	NPC86452
0.6235	Remote Similarity	NPC63284
0.6224	Remote Similarity	NPC52820
0.6184	Remote Similarity	NPC321030
0.6176	Remote Similarity	NPC470073
0.617	Remote Similarity	NPC81195
0.6163	Remote Similarity	NPC320667
0.6163	Remote Similarity	NPC214125
0.6154	Remote Similarity	NPC61321
0.6154	Remote Similarity	NPC78058
0.6154	Remote Similarity	NPC234822
0.6154	Remote Similarity	NPC135639
0.6154	Remote Similarity	NPC143344
0.6136	Remote Similarity	NPC120699
0.6136	Remote Similarity	NPC127430
0.6129	Remote Similarity	NPC324506
0.6111	Remote Similarity	NPC473810
0.6105	Remote Similarity	NPC53240
0.61	Remote Similarity	NPC477964
0.61	Remote Similarity	NPC233932
0.6098	Remote Similarity	NPC96272
0.6087	Remote Similarity	NPC319913
0.6078	Remote Similarity	NPC474828
0.6078	Remote Similarity	NPC68001
0.6078	Remote Similarity	NPC318544
0.6078	Remote Similarity	NPC199831
0.6078	Remote Similarity	NPC474827
0.6067	Remote Similarity	NPC476560
0.6049	Remote Similarity	NPC113224
0.6023	Remote Similarity	NPC473446
0.6023	Remote Similarity	NPC473695
0.6022	Remote Similarity	NPC322672
0.598	Remote Similarity	NPC474244
0.598	Remote Similarity	NPC473289
0.5978	Remote Similarity	NPC207048
0.596	Remote Similarity	NPC175614
0.5957	Remote Similarity	NPC473525
0.5875	Remote Similarity	NPC477106
0.5875	Remote Similarity	NPC316674
0.5865	Remote Similarity	NPC477000
0.5865	Remote Similarity	NPC477001
0.5857	Remote Similarity	NPC76976
0.5849	Remote Similarity	NPC207820
0.5849	Remote Similarity	NPC474099
0.5849	Remote Similarity	NPC470072
0.5814	Remote Similarity	NPC326126
0.5789	Remote Similarity	NPC305602
0.5789	Remote Similarity	NPC17497
0.5789	Remote Similarity	NPC242930
0.5778	Remote Similarity	NPC132858
0.5778	Remote Similarity	NPC77890
0.5778	Remote Similarity	NPC267203
0.5769	Remote Similarity	NPC476877
0.575	Remote Similarity	NPC47333
0.575	Remote Similarity	NPC477461
0.575	Remote Similarity	NPC477459
0.5733	Remote Similarity	NPC34577
0.573	Remote Similarity	NPC308050
0.5714	Remote Similarity	NPC469604
0.5701	Remote Similarity	NPC476276
0.57	Remote Similarity	NPC470382
0.57	Remote Similarity	NPC119225
0.57	Remote Similarity	NPC471635
0.57	Remote Similarity	NPC476261
0.57	Remote Similarity	NPC25033
0.5682	Remote Similarity	NPC281154
0.5682	Remote Similarity	NPC264417
0.5682	Remote Similarity	NPC217095
0.5664	Remote Similarity	NPC470300
0.5664	Remote Similarity	NPC471109
0.566	Remote Similarity	NPC476876
0.566	Remote Similarity	NPC476328
0.5648	Remote Similarity	NPC21324
0.5647	Remote Similarity	NPC143396
0.5647	Remote Similarity	NPC471022
0.5647	Remote Similarity	NPC103712
0.5647	Remote Similarity	NPC291196
0.5644	Remote Similarity	NPC474129
0.5632	Remote Similarity	NPC329914
0.5632	Remote Similarity	NPC305223
0.5632	Remote Similarity	NPC329890
0.5625	Remote Similarity	NPC122521
0.5625	Remote Similarity	NPC174447
0.5625	Remote Similarity	NPC470738
0.5625	Remote Similarity	NPC251042
0.5619	Remote Similarity	NPC473254
0.561	Remote Similarity	NPC476559
0.56	Remote Similarity	NPC474974

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 NPC34672 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	65
0.1-0.2	332
0.2-0.3	4169
0.3-0.4	3655
0.4-0.5	904
0.5-0.6	25
0.6-0.7	0
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
0.6117	Remote Similarity	NPD7333	Discontinued
0.5949	Remote Similarity	NPD6949	Clinical (unspecified phase)
0.5778	Remote Similarity	NPD529	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