NPASS Compound

Structure

NPC112509 OpenBabel06302215392D 40 46 0 0 1 0 0 0 0 0999 V2000 1.0437 -3.3252 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0655 -3.5331 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2435 -4.4841 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6036 -2.7899 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.3957 -1.8118 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3474 -1.1426 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2985 -0.8336 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5064 0.1445 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4575 0.4535 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2006 -0.2156 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6654 1.4317 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.6164 1.7407 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9222 2.1008 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6132 3.0519 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9712 1.7918 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2280 2.4609 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.7230 2.1519 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4662 2.8210 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4172 2.5120 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6251 1.5339 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8820 0.8648 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9309 1.1738 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1878 0.5046 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3957 -0.4735 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7633 0.8137 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5914 2.8440 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2823 3.7950 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0593 -0.2291 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3474 0.6845 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2404 1.4935 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2349 1.3889 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6416 0.4754 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0538 -0.3336 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2617 -1.3118 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.0049 -1.9809 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9830 -1.7730 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5981 -2.8944 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4642 -3.3944 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5981 -3.8944 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0906 -1.8118 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 2 0 0 0 0 2 4 1 0 0 0 0 4 37 1 0 0 0 0 5 4 1 1 0 0 0 5 6 1 0 0 0 0 5 34 1 0 0 0 0 6 7 1 0 0 0 0 6 28 1 0 0 0 0 6 40 1 1 0 0 0 8 7 1 1 0 0 0 8 9 1 0 0 0 0 8 25 1 0 0 0 0 9 10 2 0 0 0 0 9 11 1 0 0 0 0 11 12 1 0 0 0 0 11 13 1 0 0 0 0 13 14 1 6 0 0 0 13 15 1 0 0 0 0 13 26 1 0 0 0 0 15 25 1 0 0 0 0 15 16 2 0 0 0 0 16 17 1 0 0 0 0 17 22 2 0 0 0 0 17 18 1 0 0 0 0 18 19 2 0 0 0 0 19 20 1 0 0 0 0 20 21 2 0 0 0 0 21 22 1 0 0 0 0 22 23 1 0 0 0 0 23 24 2 0 0 0 0 23 25 1 0 0 0 0 26 27 1 0 0 0 0 28 33 2 0 0 0 0 28 29 1 0 0 0 0 29 30 2 0 0 0 0 30 31 1 0 0 0 0 31 32 2 0 0 0 0 32 33 1 0 0 0 0 33 34 1 0 0 0 0 34 35 1 0 0 0 0 35 36 2 0 0 0 0 35 37 1 0 0 0 0 37 39 1 0 0 0 0 37 38 1 0 0 0 0 38 39 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	543.21
Volume:	528.969
LogP:	1.183
LogD:	1.989
LogS:	-4.261
# Rotatable Bonds:	4
TPSA:	125.28
# H-Bond Aceptor:	11
# H-Bond Donor:	1
# Rings:	7
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.532
Synthetic Accessibility Score:	5.133
Fsp3:	0.414
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.066
MDCK Permeability:	2.8492779165389948e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.019
Human Intestinal Absorption (HIA):	0.79
20% Bioavailability (F20%):	0.553
30% Bioavailability (F30%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.475
Plasma Protein Binding (PPB):	81.83881378173828%
Volume Distribution (VD):	0.885
Pgp-substrate:	21.509084701538086%

ADMET: Metabolism

CYP1A2-inhibitor:	0.009
CYP1A2-substrate:	0.317
CYP2C19-inhibitor:	0.212
CYP2C19-substrate:	0.928
CYP2C9-inhibitor:	0.856
CYP2C9-substrate:	0.46
CYP2D6-inhibitor:	0.017
CYP2D6-substrate:	0.112
CYP3A4-inhibitor:	0.882
CYP3A4-substrate:	0.968

ADMET: Excretion

Clearance (CL):	3.976
Half-life (T1/2):	0.335

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.877
Drug-inuced Liver Injury (DILI):	0.994
AMES Toxicity:	0.016
Rat Oral Acute Toxicity:	0.758
Maximum Recommended Daily Dose:	0.05
Skin Sensitization:	0.749
Carcinogencity:	0.036
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.015

Download Data

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

Natural Product: NPC112509

Natural Product ID:	NPC112509
*Common Name:**	OHERQHRKBDORHU-OMBJRFEESA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	OHERQHRKBDORHU-OMBJRFEESA-N
Standard InCHI:	InChI=1S/C29H29N5O6/c1-16(35)34-25-29(39,18-10-6-8-12-20(18)33(25)26(38)28(34)13-14-28)15-21-23(37)31(3)27(2,40-4)24-30-19-11-7-5-9-17(19)22(36)32(21)24/h5-12,21,25,39H,13-15H2,1-4H3/t21-,25-,27-,29-/m1/s1
SMILES:	CC(=O)N1[C@@H]2[C@@](C[C@@H]3C(=O)N(C)[C@@](C)(c4nc5ccccc5c(=O)n34)OC)(c3ccccc3N2C(=O)C21CC2)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	71605144
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0004788] Diazanaphthalenes [CHEMONTID:0004789] Benzodiazines [CHEMONTID:0000485] Quinazolines

*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
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21049973]
NPO12352	Magnolia baillonii	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3437284]
NPO19551	Cocculus pendulus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19551	Cocculus pendulus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10921	Cercospora ligustri	Species	Mycosphaerellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12352	Magnolia baillonii	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19611	Ipomoea tuberosa	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19812	Pimelea simplex	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13189	Carex folliculata	Species	Cyperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16902	Dendroctonus brevicomis	Species	Curculionidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11741	Glycosmis parviflora	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18651	Piper lolot	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18223	Dictyostelium brefeldianum	Species	n.a.	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19146	Cosmos bipinnatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19551	Cocculus pendulus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14131	Phyllanthus maderaspatensis	Species	Phyllanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19681	Hypoxis filiformis	Species	Hypoxidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18898	Madhuca utilis	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17984	Aplysia angasi	Species	Aplysiidae	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 NPC112509 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	435
0.1-0.2	2738
0.2-0.3	13536
0.3-0.4	17721
0.4-0.5	3725
0.5-0.6	3310
0.6-0.7	1104
0.7-0.8	74
0.8-0.85	17
0.85-0.9	16
0.9-0.95	21
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 NPC112509 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	236
0.1-0.2	576
0.2-0.3	914
0.3-0.4	1674
0.4-0.5	2504
0.5-0.6	2116
0.6-0.7	1025
0.7-0.8	104
0.8-0.85	1
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