NPASS Compound

Structure

NPC469800 OpenBabel07101718242D 29 35 0 0 1 0 0 0 0 0999 V2000 -1.5838 0.1041 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6186 -0.5918 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0156 1.0262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2063 0.2172 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6034 0.2172 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4223 -0.2300 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3223 0.9680 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6186 1.0262 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0156 -0.5918 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2341 -0.4010 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9564 1.3092 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8657 -0.8649 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5597 -0.8066 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5205 -0.4976 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8015 -0.7828 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8015 1.2172 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6675 -0.2828 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0645 0.7172 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6675 0.7172 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0645 -0.2828 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4918 -1.2276 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7850 -1.2355 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9115 2.3082 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2919 -1.7695 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1690 -1.4916 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8015 -1.7828 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8015 2.2172 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1937 0.2595 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 6 1 0 0 0 0 4 2 1 6 0 0 0 4 6 1 0 0 0 0 4 8 1 0 0 0 0 5 3 1 1 0 0 0 5 9 1 0 0 0 0 5 10 1 0 0 0 0 6 21 2 0 0 0 0 7 1 1 1 0 0 0 7 11 1 0 0 0 0 7 28 1 0 0 0 0 8 11 1 0 0 0 0 8 19 1 6 0 0 0 9 12 1 0 0 0 0 9 20 1 1 0 0 0 10 22 2 0 0 0 0 11 23 1 1 0 0 0 12 13 1 0 0 0 0 12 24 1 1 0 0 0 13 14 1 0 0 0 0 13 25 1 1 0 0 0 14 10 1 6 0 0 0 14 29 1 0 0 0 0 15 17 1 0 0 0 0 15 20 1 0 0 0 0 15 26 2 0 0 0 0 16 18 1 0 0 0 0 16 19 1 0 0 0 0 16 27 2 0 0 0 0 17 2 1 1 0 0 0 17 19 1 0 0 0 0 17 28 1 0 0 0 0 18 3 1 1 0 0 0 18 20 1 0 0 0 0 18 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	438.06
Volume:	369.986
LogP:	-0.385
LogD:	-0.116
LogS:	-1.374
# Rotatable Bonds:	0
TPSA:	135.45
# H-Bond Aceptor:	9
# H-Bond Donor:	3
# Rings:	7
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.381
Synthetic Accessibility Score:	7.545
Fsp3:	0.778
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:	-5.576
MDCK Permeability:	6.796993602620205e-06
Pgp-inhibitor:	0.085
Pgp-substrate:	0.897
Human Intestinal Absorption (HIA):	0.049
20% Bioavailability (F20%):	0.008
30% Bioavailability (F30%):	0.018

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.018
Plasma Protein Binding (PPB):	70.23714447021484%
Volume Distribution (VD):	0.471
Pgp-substrate:	26.52149772644043%

ADMET: Metabolism

CYP1A2-inhibitor:	0.003
CYP1A2-substrate:	0.069
CYP2C19-inhibitor:	0.023
CYP2C19-substrate:	0.894
CYP2C9-inhibitor:	0.163
CYP2C9-substrate:	0.139
CYP2D6-inhibitor:	0.003
CYP2D6-substrate:	0.053
CYP3A4-inhibitor:	0.07
CYP3A4-substrate:	0.969

ADMET: Excretion

Clearance (CL):	3.397
Half-life (T1/2):	0.779

ADMET: Toxicity

hERG Blockers:	0.002
Human Hepatotoxicity (H-HT):	0.619
Drug-inuced Liver Injury (DILI):	0.998
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.949
Maximum Recommended Daily Dose:	0.018
Skin Sensitization:	0.325
Carcinogencity:	0.837
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.002

Download Data

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

Natural Product: NPC469800

Natural Product ID:	NPC469800
*Common Name:**	Epicoccin E
IUPAC Name:	n.a.
Synonyms:	Epicoccin E
Standard InCHIKey:	KVJHKMONYMMFLY-KZOHNSNHSA-N
Standard InCHI:	InChI=1S/C18H18N2O7S2/c21-6-1-7-11(23)8-4(6)2-17(28-7)15(26)20-9-5-3-18(20,16(27)19(8)17)29-14(10(5)22)13(25)12(9)24/h4-5,7-9,11-14,23-25H,1-3H2/t4-,5+,7+,8-,9-,11-,12+,13+,14+,17+,18+/m0/s1
SMILES:	O=C1C[C@H]2S[C@@]34C[C@@H]1[C@@H]([C@H]2O)N3C(=O)[C@]12N(C4=O)[C@@H]3[C@@H](O)[C@H]([C@H](S1)C(=O)[C@@H]3C2)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1173393
PubChem CID:	44614132
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0000060] Alpha amino acids and derivatives

*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
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17711348]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19919067]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	The fungus is isolated from the leaves of L. rhodostegia, collected in June 2007 at Nanning, Guangxi Province, China	2007-JUN	PMID[20550196]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24328302]
NPO33508	Phoma sp. OUCMDZ-1847	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24370114]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	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
IC50	1

Activity Type	# Activity
NON-MOLECULAR	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	=	1980.0	nM	PMID[536007]

☑ 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 NPC469800 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	463
0.1-0.2	6463
0.2-0.3	22793
0.3-0.4	10947
0.4-0.5	1913
0.5-0.6	91
0.6-0.7	10
0.7-0.8	5
0.8-0.85	3
0.85-0.9	6
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9265	High Similarity	NPC243412
0.8855	High Similarity	NPC8325
0.8636	High Similarity	NPC220396
0.8571	High Similarity	NPC25327
0.8321	Intermediate Similarity	NPC266910
0.8271	Intermediate Similarity	NPC211848
0.8154	Intermediate Similarity	NPC28542
0.8062	Intermediate Similarity	NPC309731
0.7669	Intermediate Similarity	NPC271115
0.7635	Intermediate Similarity	NPC276822
0.6533	Remote Similarity	NPC41162
0.6443	Remote Similarity	NPC262880
0.6443	Remote Similarity	NPC247902
0.6306	Remote Similarity	NPC88943
0.6149	Remote Similarity	NPC956
0.5789	Remote Similarity	NPC475342
0.5695	Remote Similarity	NPC17581
0.5695	Remote Similarity	NPC476155
0.5658	Remote Similarity	NPC470788

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 NPC469800 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	169
0.1-0.2	2215
0.2-0.3	4975
0.3-0.4	1544
0.4-0.5	218
0.5-0.6	28
0.6-0.7	1
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
0.6049	Remote Similarity	NPD5193	Discontinued

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