NPASS Compound

Structure

NPC482687 OpenBabel06302216182D 25 28 0 0 0 0 0 0 0 0999 V2000 0.9659 -0.7412 0.0000 C 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 -0.1305 -1.9914 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 -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 -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 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 -3.4641 -0.0000 0.0000 N 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 -4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 2.0000 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 -6.0622 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 O 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 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -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 25 1 0 0 0 0 2 3 1 0 0 0 0 2 4 1 0 0 0 0 4 5 2 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 7 25 1 0 0 0 0 8 9 1 0 0 0 0 9 10 2 0 0 0 0 9 24 1 0 0 0 0 10 22 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 13 18 2 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 14 22 1 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 17 21 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 22 23 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	339.11
Volume:	336.811
LogP:	2.752
LogD:	1.728
LogS:	-4.478
# Rotatable Bonds:	1
TPSA:	88.62
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.66
Synthetic Accessibility Score:	3.583
Fsp3:	0.263
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:	-4.923
MDCK Permeability:	1.5133347005757969e-05
Pgp-inhibitor:	0.022
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.17
20% Bioavailability (F20%):	0.002
30% Bioavailability (F30%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.055
Plasma Protein Binding (PPB):	80.21949005126953%
Volume Distribution (VD):	0.843
Pgp-substrate:	11.861090660095215%

ADMET: Metabolism

CYP1A2-inhibitor:	0.959
CYP1A2-substrate:	0.949
CYP2C19-inhibitor:	0.302
CYP2C19-substrate:	0.345
CYP2C9-inhibitor:	0.605
CYP2C9-substrate:	0.79
CYP2D6-inhibitor:	0.675
CYP2D6-substrate:	0.308
CYP3A4-inhibitor:	0.345
CYP3A4-substrate:	0.158

ADMET: Excretion

Clearance (CL):	2.157
Half-life (T1/2):	0.33

ADMET: Toxicity

hERG Blockers:	0.008
Human Hepatotoxicity (H-HT):	0.745
Drug-inuced Liver Injury (DILI):	0.914
AMES Toxicity:	0.458
Rat Oral Acute Toxicity:	0.806
Maximum Recommended Daily Dose:	0.384
Skin Sensitization:	0.478
Carcinogencity:	0.649
Eye Corrosion:	0.003
Eye Irritation:	0.049
Respiratory Toxicity:	0.971

Download Data

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

Natural Product: NPC482687

Natural Product ID:	NPC482687
*Common Name:**	COUZVMMRGYONAQ-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	COUZVMMRGYONAQ-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C19H17NO5/c1-19(2)7-6-9-13(25-19)8-12(22)14-15(9)20-16-10(17(14)23)4-5-11(21)18(16)24-3/h4-8,21-22H,1-3H3,(H,20,23)
SMILES:	CC1(C)C=Cc2c(cc(c3c2[nH]c2c(ccc(c2OC)O)c3=O)O)O1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	86765296
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001253] Quinolines and derivatives [CHEMONTID:0001908] Benzoquinolines [CHEMONTID:0000274] Acridines [CHEMONTID:0001811] Acridones

*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
NPO7267	Glycosmis chlorosperma	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24798019]
NPO7267	Glycosmis chlorosperma	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7267	Glycosmis chlorosperma	Species	Rutaceae	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
IC50	20

Activity Type	# Activity
Individual Protein	12
Others	3
Protein Complex	3
Protein Family	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1423	Individual Protein	Cyclin-dependent kinase 1	Homo sapiens	IC50	=	5300.0	nM	PMID[24798019]
NPT3240	Individual Protein	Cyclin-dependent kinase 5	Homo sapiens	IC50	=	9000.0	nM	PMID[24798019]
NPT3932	Individual Protein	Dual specificity protein kinase CLK1	Mus musculus	IC50	=	210.0	nM	PMID[24798019]
NPT1682	Individual Protein	Dual specificity protein kinase CLK2	Homo sapiens	IC50	=	680.0	nM	PMID[24798019]
NPT1683	Individual Protein	Dual specificity protein kinase CLK3	Homo sapiens	IC50	=	2300.0	nM	PMID[24798019]
NPT3231	Individual Protein	Dual specificity protein kinase CLK4	Homo sapiens	IC50	=	220.0	nM	PMID[24798019]
NPT3274	Individual Protein	Dual specificity tyrosine-phosphorylation-regulated kinase 1B	Homo sapiens	IC50	=	350.0	nM	PMID[24798019]
NPT3399	Individual Protein	Dual-specificity tyrosine-phosphorylation regulated kinase 2	Homo sapiens	IC50	=	1700.0	nM	PMID[24798019]
NPT3460	Individual Protein	Dual-specificity tyrosine-phosphorylation regulated kinase 3	Homo sapiens	IC50	=	1200.0	nM	PMID[24798019]
NPT1681	Individual Protein	Dual specificty protein kinase CLK1	Homo sapiens	IC50	=	170.0	nM	PMID[24798019]
NPT3114	Individual Protein	Dual-specificity tyrosine-phosphorylation regulated kinase 1A	Homo sapiens	IC50	=	75.0	nM	PMID[24798019]
NPT84	Individual Protein	Dual specificity tyrosine-phosphorylation-regulated kinase 1A	Rattus norvegicus	IC50	=	90.0	nM	PMID[24798019]
NPT1572	Protein Family	Glycogen synthase kinase-3	Homo sapiens	IC50	=	2000.0	nM	PMID[24798019]
NPT2	Others	Unspecified		IC50	>	10000.0	nM	PMID[24798019]
NPT2	Others	Unspecified		IC50	=	1100.0	nM	PMID[24798019]
NPT4158	Protein Complex	CDK2/Cyclin A	Homo sapiens	IC50	=	8200.0	nM	PMID[24798019]
NPT1509	Protein Complex	Cyclin-dependent kinase 5/CDK5 activator 1	Homo sapiens	IC50	>	10000.0	nM	PMID[24798019]
NPT4092	Protein Complex	CDK9/cyclin T1	Homo sapiens	IC50	=	820.0	nM	PMID[24798019]
NPT2	Others	Unspecified		IC50	=	8700.0	nM	PMID[24798019]
NPT22078	PROTEIN FAMILY	Glycogen synthase kinase-3	Sus scrofa	IC50	=	710.0	nM	PMID[24798019]

☑ 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 NPC482687 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	549
0.1-0.2	3034
0.2-0.3	11999
0.3-0.4	5546
0.4-0.5	8180
0.5-0.6	10291
0.6-0.7	2821
0.7-0.8	227
0.8-0.85	25
0.85-0.9	17
0.9-0.95	7
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 NPC482687 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	340
0.1-0.2	720
0.2-0.3	1257
0.3-0.4	2103
0.4-0.5	2527
0.5-0.6	1762
0.6-0.7	404
0.7-0.8	36
0.8-0.85	0
0.85-0.9	1
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