NPASS Compound

Structure

NPC462099 OpenBabel06302216042D 22 23 0 0 0 0 0 0 0 0999 V2000 8.6603 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6603 1.0000 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 6.9282 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 1.5000 0.0000 N 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 5.1962 -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 3.4641 -0.0000 0.0000 C 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 4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -0.5000 0.0000 N 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 -0.5000 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 0.0000 -2.0000 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 -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 -1.7321 -2.0000 0.0000 F 0 0 0 0 0 0 0 0 0 0 0 0 6.9282 -0.0000 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 5 2 3 0 0 0 4 22 1 0 0 0 0 5 6 1 0 0 0 0 6 11 2 0 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 8 9 1 0 0 0 0 9 10 2 0 0 0 0 9 13 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 20 2 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 17 18 1 0 0 0 0 18 19 2 0 0 0 0 18 21 1 0 0 0 0 19 20 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	303.14
Volume:	306.362
LogP:	2.736
LogD:	2.775
LogS:	-3.259
# Rotatable Bonds:	7
TPSA:	76.38
# H-Bond Aceptor:	5
# H-Bond Donor:	4
# Rings:	2
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.738
Synthetic Accessibility Score:	1.902
Fsp3:	0.188
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:	-4.892
MDCK Permeability:	0.00010025053779827431
Pgp-inhibitor:	0.103
Pgp-substrate:	0.957
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.001
30% Bioavailability (F30%):	0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.868
Plasma Protein Binding (PPB):	94.2707290649414%
Volume Distribution (VD):	0.766
Pgp-substrate:	10.005017280578613%

ADMET: Metabolism

CYP1A2-inhibitor:	0.957
CYP1A2-substrate:	0.743
CYP2C19-inhibitor:	0.827
CYP2C19-substrate:	0.295
CYP2C9-inhibitor:	0.752
CYP2C9-substrate:	0.331
CYP2D6-inhibitor:	0.42
CYP2D6-substrate:	0.901
CYP3A4-inhibitor:	0.673
CYP3A4-substrate:	0.16

ADMET: Excretion

Clearance (CL):	7.976
Half-life (T1/2):	0.206

ADMET: Toxicity

hERG Blockers:	0.588
Human Hepatotoxicity (H-HT):	0.805
Drug-inuced Liver Injury (DILI):	0.801
AMES Toxicity:	0.921
Rat Oral Acute Toxicity:	0.15
Maximum Recommended Daily Dose:	0.751
Skin Sensitization:	0.85
Carcinogencity:	0.159
Eye Corrosion:	0.003
Eye Irritation:	0.049
Respiratory Toxicity:	0.482

Download Data

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

Natural Product: NPC462099

Natural Product ID:	NPC462099
*Common Name:**	PCOBBVZJEWWZFR-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	PCOBBVZJEWWZFR-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C16H18FN3O2/c1-2-22-16(21)20-15-8-7-13(9-14(15)18)19-10-11-3-5-12(17)6-4-11/h3-9,19H,2,10,18H2,1H3,(H,20,21)
SMILES:	CCOC(=Nc1ccc(cc1N)NCc1ccc(cc1)F)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	121892
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000185] Phenylmethylamines [CHEMONTID:0004204] Phenylbenzamines

*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
NPO8809	Cynanchum wilfordii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10217732]
NPO8809	Cynanchum wilfordii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26716755]
NPO8809	Cynanchum wilfordii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8809	Cynanchum wilfordii	Species	Apocynaceae	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	18
ED50	4
IC50	1
Others	30

Activity Type	# Activity
Cell Line	5
Organism	11
Others	3
PROTEIN COMPLEX	10
SINGLE PROTEIN	29

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT71	Cell Line	HEK293	Homo sapiens	EC50	=	1300.0	nM	PMID[15357987]
NPT616	Cell Line	MDCK	Canis lupus familiaris	Ratio	=	1.13	n.a.	PMID[25987375]
NPT681	Cell Line	PC-12	Rattus norvegicus	Activity	=	73.92	%	PMID[29110485]
NPT681	Cell Line	PC-12	Rattus norvegicus	Activity	=	64.0	%	PMID[29110485]
NPT681	Cell Line	PC-12	Rattus norvegicus	FC	=	2.0	n.a.	PMID[29110485]
NPT19027	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Mus musculus	EC50	=	1300.0	nM	PMID[15050644]
NPT19027	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Mus musculus	EC50	=	1300.0	nM	PMID[15603955]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	47.6	mg.kg-1	PMID[17489574]
NPT2	Others	Unspecified		EC50	=	1000.0	nM	PMID[17489574]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	EC50	<	150.0	nM	PMID[17489574]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	40.0	mg.kg-1	PMID[17489574]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	ED50	=	6.6	mg.kg-1	PMID[17489574]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	0.0	%	PMID[20020710]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	49.0	%	PMID[20020710]
NPT19030	PROTEIN COMPLEX	Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3)	Homo sapiens	EC50	=	430.0	nM	PMID[21296466]
NPT19027	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Mus musculus	EC50	=	1300.0	nM	PMID[24070783]
NPT19027	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Mus musculus	Ratio	=	1.6	n.a.	PMID[24070783]
NPT27	Others	Unspecified		IC50	=	213000.0	nM	PMID[25987375]
NPT32	Organism	Mus musculus	Mus musculus	ED50	=	15.0	mg.kg-1	PMID[26716755]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Ratio	=	2.12	n.a.	PMID[29706422]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Activity	=	40.0	mV	PMID[29706422]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	EC50	=	350.0	nM	PMID[29706422]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Activity	=	40.21	%	PMID[29706422]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	EC50	=	350.0	nM	PMID[30061030]
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	0.0	%	PMID[30061030]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	15.0	%	PMID[30061030]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Ratio	=	2.12	n.a.	PMID[30061030]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Activity	=	40.21	%	PMID[30061030]
NPT19030	PROTEIN COMPLEX	Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3)	Homo sapiens	Activity	=	0.32	uM	PMID[30327146]
NPT2	Others	Unspecified		Activity	>	30.0	uM	PMID[30327146]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	1.55	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT19030	PROTEIN COMPLEX	Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3)	Homo sapiens	EC50	=	4380.0	nM	PMID[31416667]
NPT19031	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Rattus norvegicus	Ratio	=	1.6	n.a.	PMID[30655942]
NPT19032	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.4	Homo sapiens	EC50	=	5900.0	nM	PMID[30655942]
NPT19033	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.5	Homo sapiens	EC50	=	3450.0	nM	PMID[30655942]
NPT19031	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Rattus norvegicus	EC50	=	2170.0	nM	PMID[30655942]
NPT19031	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Rattus norvegicus	Activity	=	20.0	mV	PMID[30655942]
NPT19032	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.4	Homo sapiens	Activity	=	20.0	mV	PMID[30655942]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Ratio	=	2.0	n.a.	PMID[31815462]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Ratio	=	6.0	n.a.	PMID[31815462]
NPT19030	PROTEIN COMPLEX	Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3)	Homo sapiens	EC50	=	1720.0	nM	PMID[31815462]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	Activity	=	-25.37	mV	PMID[31815462]
NPT19030	PROTEIN COMPLEX	Voltage-gated potassium channel, KQT; KCNQ2(Kv7.2)/KCNQ3(Kv7.3)	Homo sapiens	Activity	=	-26.81	mV	PMID[31815462]
NPT19034	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.3	Homo sapiens	Activity	=	-39.88	mV	PMID[31815462]
NPT19032	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.4	Homo sapiens	Activity	=	-15.19	mV	PMID[31815462]
NPT19033	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.5	Homo sapiens	Activity	=	-21.95	mV	PMID[31815462]
NPT19028	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.2	Homo sapiens	EC50	=	930.0	nM	PMID[31815462]
NPT19034	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.3	Homo sapiens	EC50	=	3900.0	nM	PMID[31815462]
NPT19032	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.4	Homo sapiens	EC50	=	1980.0	nM	PMID[31815462]
NPT19033	SINGLE PROTEIN	Voltage-gated potassium channel subunit Kv7.5	Homo sapiens	EC50	=	800.0	nM	PMID[31815462]
NPT20556	SINGLE PROTEIN	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	7.961	%	DOI[10.6019/CHEMBL4495564]
NPT20555	ORGANISM	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	-0.12	%	DOI[10.6019/CHEMBL4495565]

☑ 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 NPC462099 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	157
0.1-0.2	3797
0.2-0.3	17110
0.3-0.4	14526
0.4-0.5	5394
0.5-0.6	1640
0.6-0.7	71
0.7-0.8	1
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 NPC462099 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	113
0.1-0.2	584
0.2-0.3	1305
0.3-0.4	1424
0.4-0.5	3640
0.5-0.6	1829
0.6-0.7	243
0.7-0.8	11
0.8-0.85	0
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