NPASS Compound

Structure

NPC476158 OpenBabel07101718282D 29 35 0 0 1 0 0 0 0 0999 V2000 3.1670 -5.5978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7550 -5.2664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7930 -5.5643 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9294 -3.7091 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6978 -4.7722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6811 -1.9749 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5412 -5.3447 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6811 -5.0516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9048 -5.0516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3266 -4.5388 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 4.6811 -0.9493 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3489 -4.6976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5260 -3.3920 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7062 -4.5008 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7942 -3.2929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6811 -4.0260 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.9035 -4.3178 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4594 -3.8757 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7930 -3.5132 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.9048 -4.0260 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.2804 -4.3502 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 3.7930 -2.4877 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.2604 -3.8033 0.0000 N 0 5 0 0 0 0 0 0 0 0 0 0 3.8626 -4.5999 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 5.5693 -5.5643 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7930 -0.4365 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5693 -0.4365 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4365 -3.8012 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9294 -5.3685 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 1 7 1 0 0 0 0 2 24 1 0 0 0 0 3 8 1 0 0 0 0 3 9 2 0 0 0 0 4 10 1 0 0 0 0 4 20 1 0 0 0 0 5 7 2 0 0 0 0 5 21 1 0 0 0 0 6 11 1 0 0 0 0 6 22 1 0 0 0 0 7 12 1 0 0 0 0 8 16 1 0 0 0 0 8 25 2 0 0 0 0 9 20 1 0 0 0 0 9 29 1 0 0 0 0 10 23 1 0 0 0 0 10 29 1 0 0 0 0 11 26 2 0 0 0 0 11 27 1 0 0 0 0 12 14 1 0 0 0 0 12 17 2 0 0 0 0 13 15 2 0 0 0 0 13 17 1 0 0 0 0 13 20 1 0 0 0 0 14 18 1 0 0 0 0 14 21 2 0 0 0 0 15 18 1 0 0 0 0 15 23 1 0 0 0 0 16 19 1 0 0 0 0 16 24 1 0 0 0 0 17 24 1 0 0 0 0 18 28 2 0 0 0 0 19 20 1 0 0 0 0 19 22 1 0 0 0 0 M CHG 2 21 1 23 -1 M END $$$$

Physi-Chem Properties

Molecular Weight:	408.09
Volume:	371.146
LogP:	0.386
LogD:	0.867
LogS:	-4.011
# Rotatable Bonds:	3
TPSA:	117.69
# H-Bond Aceptor:	8
# H-Bond Donor:	5
# Rings:	7
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.487
Synthetic Accessibility Score:	6.757
Fsp3:	0.3
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:	-5.617
MDCK Permeability:	1.1306732403681963e-06
Pgp-inhibitor:	0.0
Pgp-substrate:	0.008
Human Intestinal Absorption (HIA):	0.13
20% Bioavailability (F20%):	0.01
30% Bioavailability (F30%):	0.499

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.026
Plasma Protein Binding (PPB):	77.50778198242188%
Volume Distribution (VD):	1.417
Pgp-substrate:	21.593603134155273%

ADMET: Metabolism

CYP1A2-inhibitor:	0.029
CYP1A2-substrate:	0.166
CYP2C19-inhibitor:	0.212
CYP2C19-substrate:	0.075
CYP2C9-inhibitor:	0.311
CYP2C9-substrate:	0.973
CYP2D6-inhibitor:	0.035
CYP2D6-substrate:	0.196
CYP3A4-inhibitor:	0.093
CYP3A4-substrate:	0.211

ADMET: Excretion

Clearance (CL):	3.515
Half-life (T1/2):	0.884

ADMET: Toxicity

hERG Blockers:	0.006
Human Hepatotoxicity (H-HT):	0.217
Drug-inuced Liver Injury (DILI):	0.866
AMES Toxicity:	0.121
Rat Oral Acute Toxicity:	0.388
Maximum Recommended Daily Dose:	0.926
Skin Sensitization:	0.257
Carcinogencity:	0.554
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.875

Download Data

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

Natural Product: NPC476158

Natural Product ID:	NPC476158
*Common Name:**	Discorhabdin N
IUPAC Name:	n.a.
Synonyms:	Discorhabdin N
Standard InCHIKey:	SGXJSKBEBXKZJT-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C20H16N4O4S.C2HF3O2/c25-8-3-9-20-4-10(29-9)23-15-13(20)17-12-7(5-21-14(12)18(15)28)1-2-24(17)16(8)19(20)22-6-11(26)27;3-2(4,5)1(6)7/h3,5,10,16,19,22H,1-2,4,6H2,(H2,21,23,26,27,28);(H,6,7)
SMILES:	OC(=O)C(F)(F)F.OC(=O)CNC1C2C(=O)C=C3C41CC(S3)[N-]C1=C4C3=C4C(=C[NH+]=C4C1=O)CCN23
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL541416
PubChem CID:	45266430
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001626] Phenanthrolines

*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
NPO32524	latrunculid sponges	Species	n.a.	n.a.	n.a.	South African	n.a.	PMID[15332840]

☑ 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
IC50	1

Activity Type	# Activity
Cell Line	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	2249.0	nM	PMID[489394]

☑ 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 NPC476158 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	174
0.1-0.2	2752
0.2-0.3	22765
0.3-0.4	15013
0.4-0.5	1863
0.5-0.6	123
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.7246	Intermediate Similarity	NPC475610
0.6413	Remote Similarity	NPC476252
0.626	Remote Similarity	NPC473364
0.623	Remote Similarity	NPC476143
0.616	Remote Similarity	NPC476141
0.6094	Remote Similarity	NPC477417
0.6094	Remote Similarity	NPC477419
0.6034	Remote Similarity	NPC469359
0.5864	Remote Similarity	NPC469563
0.5859	Remote Similarity	NPC477416
0.5816	Remote Similarity	NPC72688
0.5773	Remote Similarity	NPC469578
0.5714	Remote Similarity	NPC220594
0.5714	Remote Similarity	NPC469562
0.5641	Remote Similarity	NPC475410
0.5641	Remote Similarity	NPC469577
0.5634	Remote Similarity	NPC175585
0.5602	Remote Similarity	NPC13470

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 NPC476158 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	103
0.1-0.2	447
0.2-0.3	2948
0.3-0.4	4819
0.4-0.5	750
0.5-0.6	83
0.6-0.7	0
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
0.6187	Remote Similarity	NPD2090	Approved
0.6144	Remote Similarity	NPD3970	Phase 3
0.6118	Remote Similarity	NPD4444	Discontinued
0.6084	Remote Similarity	NPD2099	Approved
0.6078	Remote Similarity	NPD3285	Discontinued
0.6058	Remote Similarity	NPD2147	Approved
0.5986	Remote Similarity	NPD2100	Approved
0.5909	Remote Similarity	NPD3969	Clinical (unspecified phase)
0.5903	Remote Similarity	NPD1604	Approved
0.5903	Remote Similarity	NPD1605	Approved
0.589	Remote Similarity	NPD2645	Approved
0.5855	Remote Similarity	NPD4616	Suspended
0.5833	Remote Similarity	NPD5323	Approved
0.5822	Remote Similarity	NPD3159	Discontinued
0.5811	Remote Similarity	NPD3572	Approved
0.5811	Remote Similarity	NPD1806	Approved
0.5811	Remote Similarity	NPD3571	Approved
0.5806	Remote Similarity	NPD5299	Approved
0.5786	Remote Similarity	NPD6077	Discontinued
0.5762	Remote Similarity	NPD4073	Discontinued
0.5682	Remote Similarity	NPD1749	Approved
0.5677	Remote Similarity	NPD5664	Approved
0.5646	Remote Similarity	NPD1263	Approved
0.5602	Remote Similarity	NPD2014	Approved
0.5602	Remote Similarity	NPD2016	Approved
0.5602	Remote Similarity	NPD2013	Approved
0.56	Remote Similarity	NPD2838	Clinical (unspecified phase)

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