NPASS Compound

Structure

NPC131129 OpenBabel06302215582D 40 46 0 0 1 0 0 0 0 0999 V2000 -2.8344 -4.0873 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2466 -4.8963 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2955 -4.5873 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4865 -5.1751 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -1.2955 -3.5873 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.2466 -3.2783 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5556 -2.3272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5337 -2.1193 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8865 -1.5841 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.1955 -0.6330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5263 0.1101 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5318 0.0056 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2113 -0.6635 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0773 -0.1635 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.0284 -0.4726 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2363 -1.4507 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7715 0.1966 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5636 1.1747 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4297 1.6747 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1728 1.0056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1510 1.2135 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.7661 0.0920 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5342 2.6692 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 1.6126 1.4837 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8694 0.8146 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1251 0.9191 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8682 1.5883 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7343 1.0883 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6478 1.4950 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -0.0022 2.0883 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2101 3.0664 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.2046 3.1709 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7046 4.0370 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6114 2.2574 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.9113 1.6815 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0034 1.3146 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.2113 2.2927 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4578 3.0359 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.2058 2.3973 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5556 -5.8474 0.0000 Br 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 2 40 1 0 0 0 0 3 4 1 0 0 0 0 3 5 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 7 9 1 0 0 0 0 9 10 1 0 0 0 0 11 10 1 6 0 0 0 11 12 1 0 0 0 0 11 28 1 0 0 0 0 12 13 1 1 0 0 0 12 26 1 0 0 0 0 13 14 1 0 0 0 0 14 25 1 0 0 0 0 14 15 1 0 0 0 0 15 16 2 0 0 0 0 15 17 1 0 0 0 0 17 22 1 0 0 0 0 17 18 2 0 0 0 0 18 19 1 0 0 0 0 19 20 2 0 0 0 0 19 23 1 0 0 0 0 20 21 1 0 0 0 0 20 22 1 0 0 0 0 24 18 1 6 0 0 0 24 25 1 0 0 0 0 24 39 1 0 0 0 0 25 26 1 0 0 0 0 25 36 1 0 0 0 0 26 27 1 0 0 0 0 27 34 1 6 0 0 0 27 28 1 0 0 0 0 27 30 1 0 0 0 0 28 29 1 1 0 0 0 30 31 1 0 0 0 0 30 35 1 6 0 0 0 31 32 1 0 0 0 0 32 33 2 0 0 0 0 32 34 1 0 0 0 0 36 37 1 0 0 0 0 37 38 2 0 0 0 0 37 39 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	823.82
Volume:	536.765
LogP:	2.171
LogD:	1.987
LogS:	-3.287
# Rotatable Bonds:	4
TPSA:	202.04
# H-Bond Aceptor:	13
# H-Bond Donor:	10
# Rings:	7
# Heavy Atoms:	18

MedChem Properties

QED Drug-Likeness Score:	0.214
Synthetic Accessibility Score:	6.708
Fsp3:	0.455
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	1
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.739
MDCK Permeability:	1.6967080227914266e-05
Pgp-inhibitor:	0.042
Pgp-substrate:	0.997
Human Intestinal Absorption (HIA):	0.972
20% Bioavailability (F20%):	0.015
30% Bioavailability (F30%):	0.682

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.696
Plasma Protein Binding (PPB):	97.77690887451172%
Volume Distribution (VD):	0.86
Pgp-substrate:	6.497578144073486%

ADMET: Metabolism

CYP1A2-inhibitor:	0.08
CYP1A2-substrate:	0.213
CYP2C19-inhibitor:	0.357
CYP2C19-substrate:	0.057
CYP2C9-inhibitor:	0.533
CYP2C9-substrate:	0.122
CYP2D6-inhibitor:	0.277
CYP2D6-substrate:	0.532
CYP3A4-inhibitor:	0.928
CYP3A4-substrate:	0.15

ADMET: Excretion

Clearance (CL):	2.606
Half-life (T1/2):	0.261

ADMET: Toxicity

hERG Blockers:	0.008
Human Hepatotoxicity (H-HT):	0.126
Drug-inuced Liver Injury (DILI):	0.959
AMES Toxicity:	0.031
Rat Oral Acute Toxicity:	0.978
Maximum Recommended Daily Dose:	0.956
Skin Sensitization:	0.126
Carcinogencity:	0.101
Eye Corrosion:	0.003
Eye Irritation:	0.003
Respiratory Toxicity:	0.95

Download Data

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

Natural Product: NPC131129

Natural Product ID:	NPC131129
*Common Name:**	LGZDEGUJXJWYMR-MAMHWAFJSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	LGZDEGUJXJWYMR-MAMHWAFJSA-N
Standard InCHI:	InChI=1S/C22H21Br4ClN10O3/c23-6-1-7(31-14(6)25)16(38)30-2-4-5-3-37-17(39)10-8(9(24)15(26)32-10)13-22(37,36-19(28)33-13)11(5)21(12(4)27)18(40)34-20(29)35-21/h1,4-5,11-13,18,31-32,40H,2-3H2,(H,30,38)(H3,28,33,36)(H3,29,34,35)/t4-,5-,11+,12+,13+,18+,21+,22-/m0/s1
SMILES:	c1c(c(Br)[nH]c1C(=O)NC[C@H]1[C@@H]2CN3C(=O)c4c(c(c(Br)[nH]4)Br)[C@@H]4[C@@]3([C@H]2[C@@]2([C@@H]1Cl)[C@H](NC(=N)N2)O)NC(=N)N4)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	22833276
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0001093] Carboxylic acid derivatives [CHEMONTID:0000475] Carboxylic acid amides [CHEMONTID:0004817] 2-heteroaryl carboxamides

*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
NPO17228	Streptosporangium sibiricum	Species	Streptosporangiaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21612226]
NPO17228	Streptosporangium sibiricum	Species	Streptosporangiaceae	Bacteria	n.a.	n.a.	n.a.	PMID[25960001]
NPO10821	Magnolia praecocissima	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13082	Veratrum californicum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10821	Magnolia praecocissima	Species	Magnoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13082	Veratrum californicum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13082	Veratrum californicum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16568	Vernonia cotoneaster	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17379	Lepidium syvaschicum	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17927	Streptomyces thioluteus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO17228	Streptosporangium sibiricum	Species	Streptosporangiaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO5061	Rhaphiolepis indica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11624	Didymella lethalis	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13082	Veratrum californicum	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO261	Sulfurospirillum multivorans	Species	Campylobacteraceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO10821	Magnolia praecocissima	Species	Magnoliaceae	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 NPC131129 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	608
0.1-0.2	6911
0.2-0.3	25436
0.3-0.4	4708
0.4-0.5	3307
0.5-0.6	1541
0.6-0.7	179
0.7-0.8	2
0.8-0.85	1
0.85-0.9	1
0.9-0.95	3
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 NPC131129 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	275
0.1-0.2	699
0.2-0.3	1709
0.3-0.4	2829
0.4-0.5	2893
0.5-0.6	725
0.6-0.7	20
0.7-0.8	0
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