NPASS Compound

Structure

NPC484818 OpenBabel06302216212D 32 34 0 0 1 0 0 0 0 0999 V2000 -6.0000 2.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5000 1.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 1.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0000 0.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 0.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5000 -0.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5000 -0.1340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5000 -0.1340 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0000 0.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -0.1340 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -1.0000 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 -1.0000 0.7321 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.4067 1.6456 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3849 1.8535 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6636 2.3147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6636 3.3147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2024 3.8147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0685 3.3147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0685 2.3147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2024 1.8147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0055 0.8366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6637 0.0934 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9345 1.8147 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.8005 2.3147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8005 3.3147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6665 1.8147 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 9 2 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 6 12 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 12 13 1 6 0 0 0 12 18 1 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 14 16 2 0 0 0 0 14 17 1 0 0 0 0 18 27 1 0 0 0 0 18 19 1 0 0 0 0 19 20 2 0 0 0 0 19 21 1 0 0 0 0 21 26 2 0 0 0 0 21 22 1 0 0 0 0 22 23 2 0 0 0 0 23 24 1 0 0 0 0 24 25 2 0 0 0 0 25 26 1 0 0 0 0 25 29 1 0 0 0 0 26 27 1 0 0 0 0 27 28 2 0 0 0 0 29 30 2 3 0 0 0 30 31 1 0 0 0 0 30 32 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	460.13
Volume:	441.705
LogP:	0.94
LogD:	1.087
LogS:	-3.793
# Rotatable Bonds:	9
TPSA:	119.08
# H-Bond Aceptor:	9
# H-Bond Donor:	1
# Rings:	3
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.601
Synthetic Accessibility Score:	2.949
Fsp3:	0.318
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-5.269
MDCK Permeability:	1.3836128346156329e-05
Pgp-inhibitor:	0.135
Pgp-substrate:	0.129
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.165
30% Bioavailability (F30%):	0.716

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.835
Plasma Protein Binding (PPB):	63.641998291015625%
Volume Distribution (VD):	0.517
Pgp-substrate:	49.331138610839844%

ADMET: Metabolism

CYP1A2-inhibitor:	0.028
CYP1A2-substrate:	0.871
CYP2C19-inhibitor:	0.051
CYP2C19-substrate:	0.798
CYP2C9-inhibitor:	0.207
CYP2C9-substrate:	0.714
CYP2D6-inhibitor:	0.012
CYP2D6-substrate:	0.16
CYP3A4-inhibitor:	0.499
CYP3A4-substrate:	0.935

ADMET: Excretion

Clearance (CL):	1.396
Half-life (T1/2):	0.233

ADMET: Toxicity

hERG Blockers:	0.011
Human Hepatotoxicity (H-HT):	0.567
Drug-inuced Liver Injury (DILI):	0.981
AMES Toxicity:	0.035
Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.742
Skin Sensitization:	0.196
Carcinogencity:	0.022
Eye Corrosion:	0.003
Eye Irritation:	0.012
Respiratory Toxicity:	0.005

Download Data

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

Natural Product: NPC484818

Natural Product ID:	NPC484818
*Common Name:**	IMOZEMNVLZVGJZ-QGZVFWFLSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	IMOZEMNVLZVGJZ-QGZVFWFLSA-N
Standard InCHI:	InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1
SMILES:	CCOc1cc(ccc1OC)[C@@H](CS(=O)(=O)C)N1C(=O)c2cccc(c2C1=O)N=C(C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	11561674
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001819] Isoindoles and derivatives [CHEMONTID:0002496] Isoindolines [CHEMONTID:0001820] Isoindolones [CHEMONTID:0004749] Phthalimides

*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
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32100544]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12422	Pinus massoniana	Species	Pinaceae	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
ED50	2
IC50	24
Others	14

Activity Type	# Activity
Cell Line	1
Individual Protein	17
Organism	7
Others	9
Protein Family	3
SINGLE PROTEIN	2
Tissue	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT927	Cell Line	PBMC	Homo sapiens	IC50	=	77.0	nM	PMID[19256507]
NPT208	Individual Protein	Cytochrome P450 1A2	Homo sapiens	IC50	>	10000.0	nM	PMID[19256507]
NPT212	Individual Protein	Cytochrome P450 2C9	Homo sapiens	IC50	>	10000.0	nM	PMID[19256507]
NPT213	Individual Protein	Cytochrome P450 2C19	Homo sapiens	IC50	>	10000.0	nM	PMID[19256507]
NPT110	Individual Protein	Cytochrome P450 2D6	Homo sapiens	IC50	>	10000.0	nM	PMID[19256507]
NPT109	Individual Protein	Cytochrome P450 3A4	Homo sapiens	IC50	>	10000.0	nM	PMID[19256507]
NPT4735	Individual Protein	Phosphodiesterase 4B	Homo sapiens	IC50	=	30.0	nM	PMID[29502405]
NPT2761	Individual Protein	Phosphodiesterase 4A	Homo sapiens	Inhibition	=	8.0	%	PMID[31035240]
NPT2761	Individual Protein	Phosphodiesterase 4A	Homo sapiens	Inhibition	=	57.0	%	PMID[31035240]
NPT2761	Individual Protein	Phosphodiesterase 4A	Homo sapiens	Inhibition	=	91.0	%	PMID[31035240]
NPT4735	Individual Protein	Phosphodiesterase 4B	Homo sapiens	IC50	=	27.0	nM	PMID[31035240]
NPT1464	Individual Protein	Phosphodiesterase 4D	Homo sapiens	IC50	=	33.0	nM	PMID[31035240]
NPT4735	Individual Protein	Phosphodiesterase 4B	Homo sapiens	IC50	=	24.0	nM	PMID[31013090]
NPT1464	Individual Protein	Phosphodiesterase 4D	Homo sapiens	IC50	=	35.0	nM	PMID[31013090]
NPT1464	Individual Protein	Phosphodiesterase 4D	Homo sapiens	IC50	=	74.0	nM	PMID[31099559]
NPT1464	Individual Protein	Phosphodiesterase 4D	Homo sapiens	IC50	=	540.0	nM	PMID[32115956]
NPT1464	Individual Protein	Phosphodiesterase 4D	Homo sapiens	IC50	=	47.6	nM	PMID[32100544]
NPT4735	Individual Protein	Phosphodiesterase 4B	Homo sapiens	IC50	=	74.0	nM	PMID[27713015]
NPT2560	Protein Family	Phosphodiesterase 4	Homo sapiens	IC50	=	74.0	nM	PMID[19256507]
NPT1308	Tissue	Blood	Homo sapiens	IC50	=	110.0	nM	PMID[19256507]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	0.3	mg.kg-1	PMID[19256507]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	0.03	mg.kg-1	PMID[19256507]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	5.54	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT2	Others	Unspecified		Inhibition	=	13.0	%	PMID[31035240]
NPT2	Others	Unspecified		Inhibition	=	58.0	%	PMID[31035240]
NPT2	Others	Unspecified		Inhibition	=	89.0	%	PMID[31035240]
NPT2	Others	Unspecified		IC50	=	26.0	nM	PMID[31013090]
NPT2	Others	Unspecified		IC50	=	32.0	nM	PMID[31013090]
NPT2	Others	Unspecified		IC50	=	23.0	nM	PMID[31013090]
NPT2	Others	Unspecified		IC50	=	21.0	nM	PMID[31013090]
NPT27	Others	Unspecified		Ratio	=	1.9	n.a.	PMID[31099559]
NPT2560	Protein Family	Phosphodiesterase 4	Homo sapiens	IC50	=	110.0	nM	PMID[31099559]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	13.15	%	DOI[10.6019/CHEMBL4495564]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.6639	%	DOI[10.6019/CHEMBL4495564]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.02	%	DOI[10.6019/CHEMBL4495565]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.06	%	DOI[10.6019/CHEMBL4495565]
NPT2	Others	Unspecified		IC50	=	77.0	nM	PMID[27713015]
NPT2560	Protein Family	Phosphodiesterase 4	Homo sapiens	IC50	=	74.0	nM	PMID[32255344]

☑ 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 NPC484818 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	335
0.1-0.2	2565
0.2-0.3	12521
0.3-0.4	4645
0.4-0.5	11916
0.5-0.6	9455
0.6-0.7	1239
0.7-0.8	20
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

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 NPC484818 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	203
0.1-0.2	681
0.2-0.3	1072
0.3-0.4	1367
0.4-0.5	2987
0.5-0.6	2289
0.6-0.7	532
0.7-0.8	17
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

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