NPASS Compound

Structure

NPC288402 OpenBabel06302216152D 23 25 0 0 1 0 0 0 0 0999 V2000 -2.6456 -1.5933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5116 -1.0933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3776 -1.5933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2437 -1.0933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2437 -0.0933 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3776 0.4067 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5116 0.9067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3776 1.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2437 1.9067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1097 1.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1097 0.4067 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.1097 0.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6097 -0.4593 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6097 -0.4593 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1097 -1.3253 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0 -3.5116 -0.0933 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6456 0.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7796 -0.0933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9135 0.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 1.4013 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1691 1.6092 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6691 0.7431 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 0 0 0 2 16 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 5 4 1 6 0 0 0 5 6 1 0 0 0 0 5 11 1 0 0 0 0 6 7 1 6 0 0 0 6 8 1 0 0 0 0 6 16 1 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 1 0 0 0 11 13 1 0 0 0 0 13 14 2 0 0 0 0 13 15 1 0 0 0 0 16 17 1 6 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 23 2 0 0 0 0 19 20 1 0 0 0 0 20 21 2 0 0 0 0 21 22 1 0 0 0 0 22 23 1 0 0 0 0 M CHG 1 15 -1 M END $$$$

Physi-Chem Properties

Molecular Weight:	316.2
Volume:	344.632
LogP:	4.348
LogD:	4.1
LogS:	-4.556
# Rotatable Bonds:	4
TPSA:	50.44
# H-Bond Aceptor:	3
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	3

MedChem Properties

QED Drug-Likeness Score:	0.788
Synthetic Accessibility Score:	4.051
Fsp3:	0.65
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-5.072
MDCK Permeability:	1.9953025912400335e-05
Pgp-inhibitor:	0.002
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.08
30% Bioavailability (F30%):	0.036

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.208
Plasma Protein Binding (PPB):	96.05596923828125%
Volume Distribution (VD):	1.236
Pgp-substrate:	2.2208549976348877%

ADMET: Metabolism

CYP1A2-inhibitor:	0.068
CYP1A2-substrate:	0.252
CYP2C19-inhibitor:	0.031
CYP2C19-substrate:	0.349
CYP2C9-inhibitor:	0.258
CYP2C9-substrate:	0.298
CYP2D6-inhibitor:	0.018
CYP2D6-substrate:	0.435
CYP3A4-inhibitor:	0.227
CYP3A4-substrate:	0.19

ADMET: Excretion

Clearance (CL):	1.997
Half-life (T1/2):	0.339

ADMET: Toxicity

hERG Blockers:	0.033
Human Hepatotoxicity (H-HT):	0.382
Drug-inuced Liver Injury (DILI):	0.039
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.907
Maximum Recommended Daily Dose:	0.216
Skin Sensitization:	0.096
Carcinogencity:	0.772
Eye Corrosion:	0.263
Eye Irritation:	0.442
Respiratory Toxicity:	0.961

Download Data

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

Natural Product: NPC288402

Natural Product ID:	NPC288402
*Common Name:**	ZQHJXKYYELWEOK-LCLWPZTBSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ZQHJXKYYELWEOK-LCLWPZTBSA-N
Standard InCHI:	InChI=1S/C20H28O3/c1-14-5-8-17-19(2,10-4-11-20(17,3)18(21)22)16(14)7-6-15-9-12-23-13-15/h9,12-13,16-17H,1,4-8,10-11H2,2-3H3,(H,21,22)/p-1/t16-,17+,19+,20-/m1/s1
SMILES:	C=C1CC[C@H]2[C@@](C)(CCC[C@@]2(C)C(=O)[O-])[C@@H]1CCc1ccoc1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	6955052
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0001757] Colensane and clerodane diterpenoids

*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
NPO9078	Piper hancei	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8240	Opuntia vulgaris	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9078	Piper hancei	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8240	Opuntia vulgaris	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9980	Salvia lasiantha	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9078	Piper hancei	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8240	Opuntia vulgaris	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2852	Cirsium canum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6547	Podocarpus henckelii	Species	Podocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19815	Earias insulana	Species	0lidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2406	Thermus thermophilus	Species	Thermaceae	Bacteria	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
IC50	2

Activity Type	# Activity
SINGLE PROTEIN	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT21851	SINGLE PROTEIN	Dihydroorotate dehydrogenase (fumarate)	Leishmania major	IC50	=	2624000.0	nM	PMID[474708]
NPT21851	SINGLE PROTEIN	Dihydroorotate dehydrogenase (fumarate)	Leishmania major	IC50	=	2511886.43	nM	PMID[474708]

☑ 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 NPC288402 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	267
0.1-0.2	1424
0.2-0.3	2805
0.3-0.4	7004
0.4-0.5	12974
0.5-0.6	11492
0.6-0.7	5815
0.7-0.8	714
0.8-0.85	132
0.85-0.9	51
0.9-0.95	11
0.95-1	8

Similarity Score	Similarity Level	Natural Product ID

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 NPC288402 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	249
0.1-0.2	992
0.2-0.3	1576
0.3-0.4	2732
0.4-0.5	2202
0.5-0.6	1136
0.6-0.7	249
0.7-0.8	14
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

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