NPASS Compound

Structure

CID211848 OpenBabel06191716002D 30 35 0 0 1 0 0 0 0 0999 V2000 3.1255 2.3884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4858 1.3319 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4856 0.3756 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1375 0.6974 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0026 1.8102 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3909 0.0813 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8301 1.3322 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9529 0.8550 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6583 1.8099 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6579 -0.1021 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.1025 0.8433 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0096 0.6190 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8299 0.3759 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3906 1.6285 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9092 1.2519 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3464 1.8106 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3461 -0.1014 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1744 1.3325 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5186 0.3766 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1743 0.3763 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.5188 1.3329 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.6585 2.6556 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6578 -0.9478 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7535 1.6058 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6188 2.3000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3466 2.6562 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3459 -0.9471 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1746 2.2886 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 -0.6330 0.1004 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 28 1 0 0 0 0 2 3 1 0 0 0 0 2 9 1 0 0 0 0 3 10 1 0 0 0 0 4 11 1 0 0 0 0 5 18 1 0 0 0 0 7 5 1 1 0 0 0 7 9 1 0 0 0 0 7 13 1 0 0 0 0 8 6 1 1 0 0 0 8 11 1 0 0 0 0 8 14 1 0 0 0 0 9 22 2 0 0 0 0 10 13 1 0 0 0 0 10 23 1 6 0 0 0 11 24 2 0 0 0 0 12 4 1 6 0 0 0 12 15 1 0 0 0 0 12 29 1 0 0 0 0 13 20 1 1 0 0 0 14 15 1 0 0 0 0 14 21 1 1 0 0 0 15 25 1 6 0 0 0 16 18 1 0 0 0 0 16 21 1 0 0 0 0 16 26 2 0 0 0 0 17 19 1 0 0 0 0 17 20 1 0 0 0 0 17 27 2 0 0 0 0 18 20 1 0 0 0 0 18 28 1 1 0 0 0 19 6 1 6 0 0 0 19 21 1 0 0 0 0 19 30 1 0 0 0 0 29 30 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	470.06
Volume:	405.558
LogP:	0.003
LogD:	0.29
LogS:	-3.188
# Rotatable Bonds:	1
TPSA:	115.22
# H-Bond Aceptor:	8
# H-Bond Donor:	2
# Rings:	6
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.512
Synthetic Accessibility Score:	6.556
Fsp3:	0.789
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:	-4.971
MDCK Permeability:	9.422867151442915e-06
Pgp-inhibitor:	0.376
Pgp-substrate:	0.205
Human Intestinal Absorption (HIA):	0.366
20% Bioavailability (F20%):	0.009
30% Bioavailability (F30%):	0.054

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007
Plasma Protein Binding (PPB):	62.881126403808594%
Volume Distribution (VD):	0.5
Pgp-substrate:	43.651485443115234%

ADMET: Metabolism

CYP1A2-inhibitor:	0.003
CYP1A2-substrate:	0.108
CYP2C19-inhibitor:	0.132
CYP2C19-substrate:	0.901
CYP2C9-inhibitor:	0.883
CYP2C9-substrate:	0.213
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.056
CYP3A4-inhibitor:	0.154
CYP3A4-substrate:	0.974

ADMET: Excretion

Clearance (CL):	7.985
Half-life (T1/2):	0.853

ADMET: Toxicity

hERG Blockers:	0.001
Human Hepatotoxicity (H-HT):	0.347
Drug-inuced Liver Injury (DILI):	0.993
AMES Toxicity:	0.007
Rat Oral Acute Toxicity:	0.925
Maximum Recommended Daily Dose:	0.333
Skin Sensitization:	0.415
Carcinogencity:	0.905
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.008

Download Data

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

Natural Product: NPC211848

Natural Product ID:	NPC211848
*Common Name:**	Epicoccin M
IUPAC Name:	n.a.
Synonyms:	Epicoccin M
Standard InCHIKey:	IZVLOMZFKBEMKA-FVCPCXLRSA-N
Standard InCHI:	InChI=1S/C19H22N2O6S3/c1-28-18-5-7-9(22)2-3-10(23)13(7)20(18)17(27)19-6-8-11(24)4-12(29-30-19)15(25)14(8)21(19)16(18)26/h7-8,10,12-15,23,25H,2-6H2,1H3/t7-,8-,10-,12+,13-,14-,15-,18+,19+/m0/s1
SMILES:	CS[C@]12C[C@H]3C(=O)CC[C@@H]([C@H]3N2C(=O)[C@]23C[C@H]4C(=O)C[C@H]([C@@H]([C@H]4N2C1=O)O)SS3)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1173739
PubChem CID:	46873060
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]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21612217]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24328302]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27203291]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO28129	Reticulitermes virginicus	Species	Termitoidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23676	Fleroya rubrostipulata	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18557	Epicoccum nigrum	Species	Didymellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28114	Peltophorum adnatum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23882	Cremastosperma microcarpum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27974	Swertia leduci	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28310	Phacelocarpus labillardieri	Species	Phacelocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28982	Calliandra confusa	Species	Fabaceae	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	=	4160.0	nM	PMID[537656]

☑ 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 NPC211848 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	224
0.1-0.2	5930
0.2-0.3	21536
0.3-0.4	12989
0.4-0.5	1839
0.5-0.6	152
0.6-0.7	9
0.7-0.8	7
0.8-0.85	4
0.85-0.9	3
0.9-0.95	2
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9576	High Similarity	NPC220396
0.9386	High Similarity	NPC28542
0.8908	High Similarity	NPC266910
0.8632	High Similarity	NPC309731
0.8571	High Similarity	NPC243412
0.856	High Similarity	NPC8325
0.8271	Intermediate Similarity	NPC469800
0.7846	Intermediate Similarity	NPC25327
0.76	Intermediate Similarity	NPC271115
0.7388	Intermediate Similarity	NPC41162
0.6849	Remote Similarity	NPC276822
0.6788	Remote Similarity	NPC247902
0.6788	Remote Similarity	NPC262880
0.6403	Remote Similarity	NPC97580
0.6139	Remote Similarity	NPC475342
0.6087	Remote Similarity	NPC17581
0.6087	Remote Similarity	NPC476155
0.6067	Remote Similarity	NPC88943
0.5909	Remote Similarity	NPC956
0.5865	Remote Similarity	NPC241394
0.5859	Remote Similarity	NPC47076
0.5859	Remote Similarity	NPC134504
0.5857	Remote Similarity	NPC470300
0.5816	Remote Similarity	NPC470788
0.5806	Remote Similarity	NPC322966
0.5789	Remote Similarity	NPC128303
0.5758	Remote Similarity	NPC194750
0.5758	Remote Similarity	NPC287638
0.5758	Remote Similarity	NPC233274
0.5726	Remote Similarity	NPC168017
0.5704	Remote Similarity	NPC475340
0.5643	Remote Similarity	NPC272166
0.5635	Remote Similarity	NPC178632
0.561	Remote Similarity	NPC277918

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 NPC211848 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	107
0.1-0.2	1680
0.2-0.3	5106
0.3-0.4	1886
0.4-0.5	319
0.5-0.6	50
0.6-0.7	2
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
0.623	Remote Similarity	NPD2682	Approved
0.619	Remote Similarity	NPD3713	Approved
0.619	Remote Similarity	NPD3715	Approved
0.619	Remote Similarity	NPD3714	Approved
0.5909	Remote Similarity	NPD5193	Discontinued
0.5746	Remote Similarity	NPD6920	Discontinued
0.5736	Remote Similarity	NPD1784	Approved
0.5643	Remote Similarity	NPD1000	Clinical (unspecified phase)
0.5638	Remote Similarity	NPD7751	Phase 1

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