NPASS Compound

Structure

NPC479772 OpenBabel06302216202D 35 39 0 0 1 0 0 0 0 0999 V2000 9.5984 -5.8273 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7597 -6.3720 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9825 -5.7426 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0166 -6.0015 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7578 -6.9674 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3095 -5.2944 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.3436 -5.5532 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6365 -4.8461 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 4.6365 -3.8461 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 5.3436 -3.1390 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0848 -2.1730 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.7919 -1.4659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5330 -0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7578 -1.7247 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1162 -2.6583 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1148 -2.6060 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3736 -1.6401 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5349 -1.0954 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 8.7441 -3.3831 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.6365 -3.8461 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.9294 -3.1390 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0858 -2.1513 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1948 -1.6973 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.4877 -2.4044 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -2.2480 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.9417 -3.2954 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.6365 -4.8461 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.9294 -5.5532 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9417 -5.3967 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4877 -6.2877 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.1948 -6.9949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0384 -7.9825 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.0858 -6.5409 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 8.3409 -4.8091 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 9.3395 -4.8614 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 35 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 3 34 1 0 0 0 0 4 5 2 0 0 0 0 4 6 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 8 27 1 0 0 0 0 9 10 1 0 0 0 0 9 20 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 12 14 1 0 0 0 0 14 18 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 19 1 0 0 0 0 17 18 1 0 0 0 0 20 21 1 0 0 0 0 20 27 1 0 0 0 0 21 26 1 0 0 0 0 21 22 2 0 0 0 0 22 23 1 0 0 0 0 23 24 1 0 0 0 0 24 25 2 0 0 0 0 24 26 1 0 0 0 0 27 28 1 0 0 0 0 28 33 1 0 0 0 0 28 29 2 0 0 0 0 29 30 1 0 0 0 0 30 31 1 0 0 0 0 31 32 2 0 0 0 0 31 33 1 0 0 0 0 34 35 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	540.13
Volume:	466.753
LogP:	0.243
LogD:	1.042
LogS:	-3.266
# Rotatable Bonds:	10
TPSA:	200.64
# H-Bond Aceptor:	12
# H-Bond Donor:	10
# Rings:	5
# Heavy Atoms:	13

MedChem Properties

QED Drug-Likeness Score:	0.161
Synthetic Accessibility Score:	5.149
Fsp3:	0.273
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:	-5.852
MDCK Permeability:	3.2869584174477495e-06
Pgp-inhibitor:	0.001
Pgp-substrate:	0.999
Human Intestinal Absorption (HIA):	0.525
20% Bioavailability (F20%):	0.01
30% Bioavailability (F30%):	0.037

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.477
Plasma Protein Binding (PPB):	67.28150939941406%
Volume Distribution (VD):	0.684
Pgp-substrate:	34.005531311035156%

ADMET: Metabolism

CYP1A2-inhibitor:	0.013
CYP1A2-substrate:	0.731
CYP2C19-inhibitor:	0.483
CYP2C19-substrate:	0.02
CYP2C9-inhibitor:	0.055
CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.0
CYP2D6-substrate:	0.041
CYP3A4-inhibitor:	0.162
CYP3A4-substrate:	0.089

ADMET: Excretion

Clearance (CL):	2.831
Half-life (T1/2):	0.977

ADMET: Toxicity

hERG Blockers:	0.897
Human Hepatotoxicity (H-HT):	0.997
Drug-inuced Liver Injury (DILI):	0.961
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.598
Maximum Recommended Daily Dose:	0.978
Skin Sensitization:	0.384
Carcinogencity:	0.097
Eye Corrosion:	0.003
Eye Irritation:	0.021
Respiratory Toxicity:	0.873

Download Data

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

Natural Product: NPC479772

Natural Product ID:	NPC479772
*Common Name:**	KFAZHVDFPNXCNB-WUYIMCQSSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	KFAZHVDFPNXCNB-WUYIMCQSSA-N
Standard InCHI:	InChI=1S/C22H25BrN10O2.2ClH/c23-10-4-14(27-5-10)20(35)29-7-12-11(6-28-19(34)13-2-1-3-26-13)17(15-8-30-21(24)32-15)18(12)16-9-31-22(25)33-16;;/h1-5,8-9,11-12,17-18,26-27H,6-7H2,(H,28,34)(H,29,35)(H3,24,30,32)(H3,25,31,33);2*1H/t11-,12-,17-,18-;;/m1../s1
SMILES:	c1cc(C(=O)NC[C@@H]2[C@@H](CNC(=O)c3cc(c[nH]3)Br)[C@H](c3c[nH]c(=N)[nH]3)[C@H]2c2c[nH]c(=N)[nH]2)[nH]c1.Cl.Cl
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	44584044
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
NPO28241	Agelas conifera	Species	Agelasidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9784176]
NPO28241	Agelas conifera	Species	Agelasidae	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
Others	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	Activity	=	35.0	%	PMID[9784176]

☑ 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 NPC479772 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	1089
0.1-0.2	15921
0.2-0.3	18434
0.3-0.4	2964
0.4-0.5	2505
0.5-0.6	1424
0.6-0.7	293
0.7-0.8	42
0.8-0.85	8
0.85-0.9	4
0.9-0.95	10
0.95-1	3

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 NPC479772 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	362
0.1-0.2	1103
0.2-0.3	1800
0.3-0.4	2250
0.4-0.5	2063
0.5-0.6	1310
0.6-0.7	245
0.7-0.8	17
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