NPASS Compound

Structure

NPC164862 OpenBabel06302215192D 25 27 0 0 1 0 0 0 0 0999 V2000 -2.3383 0.4500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5588 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5588 -0.9000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7794 0.4500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7794 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.8000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 2.7000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7794 3.1500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5588 2.7000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3383 3.1500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7883 3.9294 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8883 3.9294 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1177 2.7000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1177 1.8000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3383 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5588 1.8000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7794 1.3500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7794 0.4500 0.0000 C 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 0.0000 -0.9000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5588 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5588 -1.8000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7794 -2.2500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3383 -2.2500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3383 -3.1500 0.0000 C 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 2 4 1 0 0 0 0 4 19 2 0 0 0 0 4 5 1 0 0 0 0 5 6 2 0 0 0 0 6 17 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 9 8 1 1 0 0 0 9 10 1 0 0 0 0 9 16 1 0 0 0 0 10 11 1 0 0 0 0 10 12 1 0 0 0 0 10 13 1 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 17 1 0 0 0 0 16 22 1 1 0 0 0 17 18 2 0 0 0 0 18 19 1 0 0 0 0 18 21 1 0 0 0 0 19 20 1 0 0 0 0 22 23 2 0 0 0 0 22 24 1 0 0 0 0 24 25 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	346.21
Volume:	370.718
LogP:	4.544
LogD:	3.778
LogS:	-4.35
# Rotatable Bonds:	3
TPSA:	66.76
# H-Bond Aceptor:	4
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.615
Synthetic Accessibility Score:	3.779
Fsp3:	0.667
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.735
MDCK Permeability:	1.8887129044742323e-05
Pgp-inhibitor:	0.757
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.014
20% Bioavailability (F20%):	0.989
30% Bioavailability (F30%):	0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.487
Plasma Protein Binding (PPB):	98.85968780517578%
Volume Distribution (VD):	2.416
Pgp-substrate:	1.6554149389266968%

ADMET: Metabolism

CYP1A2-inhibitor:	0.204
CYP1A2-substrate:	0.925
CYP2C19-inhibitor:	0.449
CYP2C19-substrate:	0.875
CYP2C9-inhibitor:	0.421
CYP2C9-substrate:	0.927
CYP2D6-inhibitor:	0.306
CYP2D6-substrate:	0.806
CYP3A4-inhibitor:	0.359
CYP3A4-substrate:	0.434

ADMET: Excretion

Clearance (CL):	4.21
Half-life (T1/2):	0.238

ADMET: Toxicity

hERG Blockers:	0.006
Human Hepatotoxicity (H-HT):	0.169
Drug-inuced Liver Injury (DILI):	0.027
AMES Toxicity:	0.043
Rat Oral Acute Toxicity:	0.439
Maximum Recommended Daily Dose:	0.735
Skin Sensitization:	0.919
Carcinogencity:	0.061
Eye Corrosion:	0.003
Eye Irritation:	0.834
Respiratory Toxicity:	0.724

Download Data

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

Natural Product: NPC164862

Natural Product ID:	NPC164862
*Common Name:**	IIJLVJMZYPZQLW-YCRPNKLZSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	IIJLVJMZYPZQLW-YCRPNKLZSA-N
Standard InCHI:	InChI=1S/C21H30O4/c1-12(2)14-11-13-7-8-15-20(3,4)9-6-10-21(15,19(24)25-5)16(13)18(23)17(14)22/h11-12,15,22-23H,6-10H2,1-5H3/t15-,21+/m0/s1
SMILES:	CC(C)c1cc2CC[C@H]3C(C)(C)CCC[C@@]3(c2c(c1O)O)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	11336941
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] 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
NPO6095	Xanthoparmelia verruculifera	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28354	Tragacantha stipulosa	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO28520	Heliotropium subulatum	Species	Heliotropiaceae	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
EC50	2
IC50	4
Kd	1
Others	5

Activity Type	# Activity
Cell Line	2
Individual Protein	8
Others	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	IC50	=	865.0	nM	PMID[543180]
NPT1495	Individual Protein	Geranylgeranyl pyrophosphate synthetase	Homo sapiens	IC50	=	15200.0	nM	PMID[543180]
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	IC50	=	470.0	nM	PMID[543180]
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	IC50	=	870.0	nM	PMID[543180]
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	Kd	=	360.0	nM	PMID[543180]
NPT461	Cell Line	PANC-1	Homo sapiens	EC50	=	12000.0	nM	PMID[543180]
NPT783	Cell Line	MIA PaCa-2	Homo sapiens	EC50	=	13000.0	nM	PMID[543180]
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	Kdiss	=	1.55	10'-4/s	PMID[543180]
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	Ka	=	4.25	10'2/M/s	PMID[543180]
NPT1384	Individual Protein	Farnesyl diphosphate synthase	Homo sapiens	TIME	=	1.792	hr	PMID[543180]
NPT27	Others	Unspecified		log Pe	=	-4.96	n.a.	PMID[543179]
NPT2	Others	Unspecified		Ratio IC50	>=	20.0	n.a.	PMID[543180]

☑ 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 NPC164862 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

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 NPC164862 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

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