NPASS Compound

Structure

NPC227406 OpenBabel06302215262D 30 35 0 0 1 0 0 0 0 0999 V2000 2.7520 -0.9625 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5395 -0.3903 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4377 0.5778 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5485 0.9737 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7609 0.4016 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8627 -0.5665 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9734 0.9737 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2742 1.8995 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5750 0.9737 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.9737 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0000 1.9471 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8645 2.4498 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8557 2.4341 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8625 3.3964 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6992 3.8717 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5292 3.3847 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5224 2.4224 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6857 1.9471 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6857 0.9737 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6857 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5501 -0.5027 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8300 -0.4870 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6233 -1.4269 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3344 -1.5207 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8671 -2.4286 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3473 -3.3439 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7196 -0.6389 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3221 -2.2140 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6925 -0.9931 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 6 2 0 0 0 0 1 2 1 0 0 0 0 2 3 2 0 0 0 0 3 4 1 0 0 0 0 4 9 1 0 0 0 0 4 5 2 0 0 0 0 5 6 1 0 0 0 0 5 7 1 0 0 0 0 7 8 2 0 0 0 0 8 9 1 0 0 0 0 10 7 1 6 0 0 0 10 28 1 0 0 0 0 10 11 1 0 0 0 0 10 19 1 0 0 0 0 11 12 2 0 0 0 0 11 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 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 20 21 2 0 0 0 0 20 22 1 0 0 0 0 22 28 1 0 0 0 0 22 23 1 0 0 0 0 22 30 1 6 0 0 0 23 24 1 0 0 0 0 23 29 1 6 0 0 0 24 25 1 1 0 0 0 24 27 1 0 0 0 0 25 26 1 0 0 0 0 28 27 1 1 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	406.12
Volume:	388.736
LogP:	1.973
LogD:	1.864
LogS:	-4.148
# Rotatable Bonds:	2
TPSA:	123.09
# H-Bond Aceptor:	8
# H-Bond Donor:	4
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.49
Synthetic Accessibility Score:	4.352
Fsp3:	0.273
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:	-5.318
MDCK Permeability:	5.010758741263999e-06
Pgp-inhibitor:	0.016
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.433
20% Bioavailability (F20%):	0.033
30% Bioavailability (F30%):	0.081

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.602
Plasma Protein Binding (PPB):	71.86343383789062%
Volume Distribution (VD):	0.929
Pgp-substrate:	25.33534812927246%

ADMET: Metabolism

CYP1A2-inhibitor:	0.049
CYP1A2-substrate:	0.269
CYP2C19-inhibitor:	0.119
CYP2C19-substrate:	0.797
CYP2C9-inhibitor:	0.154
CYP2C9-substrate:	0.868
CYP2D6-inhibitor:	0.02
CYP2D6-substrate:	0.16
CYP3A4-inhibitor:	0.336
CYP3A4-substrate:	0.905

ADMET: Excretion

Clearance (CL):	2.096
Half-life (T1/2):	0.665

ADMET: Toxicity

hERG Blockers:	0.008
Human Hepatotoxicity (H-HT):	0.082
Drug-inuced Liver Injury (DILI):	0.982
AMES Toxicity:	0.679
Rat Oral Acute Toxicity:	0.7
Maximum Recommended Daily Dose:	0.836
Skin Sensitization:	0.733
Carcinogencity:	0.705
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.446

Download Data

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

Natural Product: NPC227406

Natural Product ID:	NPC227406
*Common Name:**	GESJIKYYEGPJJU-PYDYAWQMSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	GESJIKYYEGPJJU-PYDYAWQMSA-N
Standard InCHI:	InChI=1S/C22H18N2O6/c25-10-16-18(27)22(29)19(30-16)21(13-9-23-14-7-3-1-5-11(13)14)17(26)12-6-2-4-8-15(12)24(21)20(22)28/h1-9,16,18-19,23,25,27,29H,10H2/t16-,18-,19+,21-,22-/m0/s1
SMILES:	c1ccc2c(c1)c(c[nH]2)[C@]12C(=O)c3ccccc3N2C(=O)[C@@]2([C@H]([C@H](CO)O[C@H]12)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	45112299
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0002497] Indoles [CHEMONTID:0004196] 3-alkylindoles

*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
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11678654]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15787451]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	Roots	Anhui, China	n.a.	PMID[22694318]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	Roots	n.a.	n.a.	PMID[32004936]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4554	Isatis tinctoria	Species	Brassicaceae	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 NPC227406 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	413
0.1-0.2	2317
0.2-0.3	11767
0.3-0.4	18361
0.4-0.5	5482
0.5-0.6	2447
0.6-0.7	1691
0.7-0.8	219
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

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 NPC227406 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	209
0.1-0.2	578
0.2-0.3	924
0.3-0.4	2343
0.4-0.5	2809
0.5-0.6	1725
0.6-0.7	523
0.7-0.8	39
0.8-0.85	0
0.85-0.9	0
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