NPASS Compound

Structure

NPC48637 OpenBabel06302215372D 30 34 0 0 1 0 0 0 0 0999 V2000 -4.2072 -3.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3412 -3.1691 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4752 -3.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6092 -3.1691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6092 -2.1691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7431 -1.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7431 -0.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6092 -0.1691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4752 -0.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4752 -1.6691 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3412 -2.1691 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2072 -1.6691 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 -5.1208 -2.0759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4298 -3.0269 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4080 -3.2348 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0771 -2.4917 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7681 -1.5406 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7899 -1.3327 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2899 -0.4667 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6967 0.4468 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3118 -0.6746 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4372 -0.7975 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4153 -1.0054 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0552 -2.6996 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7244 -1.9565 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3412 -0.1691 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3412 0.8309 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4013 0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4067 0.9135 0.0000 C 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 11 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 10 2 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 7 30 1 0 0 0 0 7 8 1 0 0 0 0 8 9 2 0 0 0 0 8 28 1 0 0 0 0 9 10 1 0 0 0 0 9 26 1 0 0 0 0 11 10 1 1 0 0 0 11 12 1 0 0 0 0 12 21 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 15 16 1 0 0 0 0 16 17 2 0 0 0 0 16 24 1 0 0 0 0 17 18 1 0 0 0 0 17 22 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 22 23 1 0 0 0 0 24 25 1 0 0 0 0 26 27 1 0 0 0 0 28 29 1 0 0 0 0 29 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	413.15
Volume:	400.359
LogP:	1.854
LogD:	2.356
LogS:	-3.846
# Rotatable Bonds:	4
TPSA:	75.69
# H-Bond Aceptor:	8
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.709
Synthetic Accessibility Score:	3.553
Fsp3:	0.409
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:	-4.818
MDCK Permeability:	3.929354716092348e-05
Pgp-inhibitor:	0.956
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.005
30% Bioavailability (F30%):	0.099

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.989
Plasma Protein Binding (PPB):	83.56659698486328%
Volume Distribution (VD):	1.525
Pgp-substrate:	10.500731468200684%

ADMET: Metabolism

CYP1A2-inhibitor:	0.205
CYP1A2-substrate:	0.958
CYP2C19-inhibitor:	0.885
CYP2C19-substrate:	0.936
CYP2C9-inhibitor:	0.585
CYP2C9-substrate:	0.85
CYP2D6-inhibitor:	0.764
CYP2D6-substrate:	0.884
CYP3A4-inhibitor:	0.948
CYP3A4-substrate:	0.926

ADMET: Excretion

Clearance (CL):	5.211
Half-life (T1/2):	0.158

ADMET: Toxicity

hERG Blockers:	0.159
Human Hepatotoxicity (H-HT):	0.141
Drug-inuced Liver Injury (DILI):	0.126
AMES Toxicity:	0.173
Rat Oral Acute Toxicity:	0.595
Maximum Recommended Daily Dose:	0.888
Skin Sensitization:	0.037
Carcinogencity:	0.633
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.852

Download Data

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

Natural Product: NPC48637

Natural Product ID:	NPC48637
*Common Name:**	AKNNEGZIBPJZJG-QNSVNVJESA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	AKNNEGZIBPJZJG-QNSVNVJESA-N
Standard InCHI:	InChI=1S/C22H23NO7/c1-23-8-7-11-9-14-20(29-10-28-14)21(27-4)15(11)17(23)18-12-5-6-13(25-2)19(26-3)16(12)22(24)30-18/h5-6,9,17-18H,7-8,10H2,1-4H3/t17-,18?/m1/s1
SMILES:	CN1CCc2cc3c(c(c2[C@@H]1C1c2ccc(c(c2C(=O)O1)OC)OC)OC)OCO3
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	19728
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002188] Phthalide isoquinolines

*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
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	fruit	n.a.	PMID[10606547]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15019787]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22029392]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23517479]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	Bark	n.a.	n.a.	Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	Fruit Juice	n.a.	n.a.	Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	Latex Exudate	n.a.	n.a.	Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	Pericarp	n.a.	n.a.	Database[FooDB]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	Root Bark	n.a.	n.a.	Database[FooDB]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18366	Papaver commutatum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO19787	Citrus sinensis	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9498	Papaver somniferum	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18366	Papaver commutatum	Species	Papaveraceae	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

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

☑ 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 NPC48637 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	331
0.1-0.2	1536
0.2-0.3	5110
0.3-0.4	11629
0.4-0.5	5481
0.5-0.6	8074
0.6-0.7	9377
0.7-0.8	1078
0.8-0.85	50
0.85-0.9	14
0.9-0.95	1
0.95-1	16

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 NPC48637 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	211
0.1-0.2	671
0.2-0.3	1158
0.3-0.4	2224
0.4-0.5	2446
0.5-0.6	1702
0.6-0.7	629
0.7-0.8	104
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	3

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