NPASS Compound

Structure

NPC336114 OpenBabel06302215322D 23 24 0 0 0 0 0 0 0 0999 V2000 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 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 -0.8660 -1.5000 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 -1.7321 -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 -2.5981 1.5000 0.0000 O 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 -4.3301 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 -5.1962 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -1.0000 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 -7.7942 -1.5000 0.0000 O 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 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 O 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 -2.5981 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 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 3 19 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 5 6 1 0 0 0 0 5 22 1 0 0 0 0 6 7 1 0 0 0 0 6 18 2 0 0 0 0 7 8 2 0 0 0 0 7 9 1 0 0 0 0 9 10 2 0 0 0 0 10 11 1 0 0 0 0 11 16 2 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 14 17 1 0 0 0 0 15 16 1 0 0 0 0 18 19 1 0 0 0 0 18 20 1 0 0 0 0 20 21 1 0 0 0 0 22 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	314.12
Volume:	325.631
LogP:	2.833
LogD:	3.095
LogS:	-3.986
# Rotatable Bonds:	6
TPSA:	64.99
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	2
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.654
Synthetic Accessibility Score:	2.085
Fsp3:	0.167
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:	-4.804
MDCK Permeability:	2.2104126401245594e-05
Pgp-inhibitor:	0.043
Pgp-substrate:	0.003
Human Intestinal Absorption (HIA):	0.01
20% Bioavailability (F20%):	0.008
30% Bioavailability (F30%):	0.16

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.153
Plasma Protein Binding (PPB):	97.49934387207031%
Volume Distribution (VD):	0.598
Pgp-substrate:	3.045623302459717%

ADMET: Metabolism

CYP1A2-inhibitor:	0.958
CYP1A2-substrate:	0.934
CYP2C19-inhibitor:	0.866
CYP2C19-substrate:	0.703
CYP2C9-inhibitor:	0.623
CYP2C9-substrate:	0.943
CYP2D6-inhibitor:	0.474
CYP2D6-substrate:	0.932
CYP3A4-inhibitor:	0.876
CYP3A4-substrate:	0.481

ADMET: Excretion

Clearance (CL):	11.812
Half-life (T1/2):	0.794

ADMET: Toxicity

hERG Blockers:	0.149
Human Hepatotoxicity (H-HT):	0.27
Drug-inuced Liver Injury (DILI):	0.836
AMES Toxicity:	0.698
Rat Oral Acute Toxicity:	0.509
Maximum Recommended Daily Dose:	0.404
Skin Sensitization:	0.921
Carcinogencity:	0.634
Eye Corrosion:	0.005
Eye Irritation:	0.947
Respiratory Toxicity:	0.898

Download Data

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

Natural Product: NPC336114

Natural Product ID:	NPC336114
*Common Name:**	ZWNLSRDFHQCTQW-RMKNXTFCSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ZWNLSRDFHQCTQW-RMKNXTFCSA-N
Standard InCHI:	InChI=1S/C18H18O5/c1-21-14-10-16(22-2)18(17(11-14)23-3)15(20)9-6-12-4-7-13(19)8-5-12/h4-11,19H,1-3H3/b9-6+
SMILES:	COc1cc(c(C(=O)/C=C/c2ccc(cc2)O)c(c1)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	5986673
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003467] Linear 1,3-diarylpropanoids [CHEMONTID:0003496] Cinnamylphenols

*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
NPO25543	Vitex leptobotrys	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24404757]
NPO25543	Vitex leptobotrys	Species	Lamiaceae	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	1
IC50	5
Others	11

Activity Type	# Activity
Cell Line	10
Individual Protein	1
Organism	3
Others	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell Line	HeLa	Homo sapiens	IC50	=	40600.0	nM	PMID[25629304]
NPT81	Cell Line	A549	Homo sapiens	IC50	=	49400.0	nM	PMID[25629304]
NPT65	Cell Line	HepG2	Homo sapiens	IC50	=	37000.0	nM	PMID[25629304]
NPT1229	Cell Line	Huh-7	Homo sapiens	Survival	=	45.0	%	PMID[28214231]
NPT492	Cell Line	Caco-2	Homo sapiens	Survival	=	24.0	%	PMID[28214231]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	Survival	=	32.0	%	PMID[28214231]
NPT393	Cell Line	HCT-116	Homo sapiens	Survival	=	17.0	%	PMID[28214231]
NPT306	Cell Line	PC-3	Homo sapiens	Survival	=	33.0	%	PMID[28214231]
NPT2378	Cell Line	NCI-H727	Homo sapiens	Survival	=	42.0	%	PMID[28214231]
NPT941	Cell Line	HaCaT	Homo sapiens	Survival	=	16.0	%	PMID[28214231]
NPT31	Individual Protein	Cyclooxygenase-2	Homo sapiens	Inhibition	=	62.2	%	PMID[31255927]
NPT164	Organism	Human herpesvirus 4	Human herpesvirus 4	EC50	=	15000.0	nM	PMID[24404757]
NPT27	Others	Unspecified		CC50	=	24400.0	nM	PMID[24404757]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	Inhibition	=	77.0	%	PMID[24404757]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	IC50	<	15200.0	nM	PMID[24404757]
NPT2	Others	Unspecified		Survival	=	65.0	%	PMID[28214231]
NPT2	Others	Unspecified		IC50	>	200000.0	nM	PMID[28242551]

☑ 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 NPC336114 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	336
0.1-0.2	1675
0.2-0.3	4572
0.3-0.4	11265
0.4-0.5	6395
0.5-0.6	3924
0.6-0.7	5937
0.7-0.8	5369
0.8-0.85	1949
0.85-0.9	870
0.9-0.95	314
0.95-1	91

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 NPC336114 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	315
0.1-0.2	986
0.2-0.3	1483
0.3-0.4	2635
0.4-0.5	1904
0.5-0.6	1217
0.6-0.7	415
0.7-0.8	141
0.8-0.85	40
0.85-0.9	9
0.9-0.95	3
0.95-1	2

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