NPASS Compound

Structure

NPC155230 OpenBabel07101719522D 30 30 0 0 1 0 0 0 0 0999 V2000 2.1730 1.4177 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7247 3.0908 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6072 -1.4659 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7071 -0.7071 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7071 3.4392 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4709 3.3014 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7638 4.0085 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4368 3.5602 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2321 1.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7321 2.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7979 3.7497 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2321 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1439 2.8531 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4659 2.1248 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8660 3.2321 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0908 4.4568 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 1.8660 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.8660 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 3.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7321 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.1248 4.1980 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 2.7321 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -8.1099 3.1119 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3496 5.4227 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1248 -1.4659 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6072 4.1980 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4659 0.6072 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 14 1 0 0 0 0 2 14 1 0 0 0 0 4 24 1 0 0 0 0 5 25 1 0 0 0 0 6 7 1 0 0 0 0 6 8 2 0 0 0 0 7 11 2 0 0 0 0 8 13 1 0 0 0 0 9 10 1 0 0 0 0 9 12 1 0 0 0 0 10 16 1 0 0 0 0 11 17 1 0 0 0 0 12 22 1 0 0 0 0 13 26 2 0 0 0 0 15 3 1 1 0 0 0 15 19 1 0 0 0 0 15 24 1 0 0 0 0 16 20 1 0 0 0 0 16 23 1 6 0 0 0 17 23 2 3 0 0 0 17 27 1 0 0 0 0 18 14 1 1 0 0 0 18 21 1 0 0 0 0 18 25 1 0 0 0 0 19 22 2 3 0 0 0 19 28 1 0 0 0 0 20 25 1 0 0 0 0 20 29 2 0 0 0 0 21 24 1 0 0 0 0 21 30 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	420.24
Volume:	432.699
LogP:	0.519
LogD:	1.426
LogS:	-2.35
# Rotatable Bonds:	7
TPSA:	132.51
# H-Bond Aceptor:	9
# H-Bond Donor:	5
# Rings:	1
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.261
Synthetic Accessibility Score:	4.552
Fsp3:	0.429
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.241
MDCK Permeability:	2.3198042526928475e-06
Pgp-inhibitor:	0.002
Pgp-substrate:	0.956
Human Intestinal Absorption (HIA):	0.029
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.026

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.167
Plasma Protein Binding (PPB):	90.2222671508789%
Volume Distribution (VD):	1.395
Pgp-substrate:	10.39084529876709%

ADMET: Metabolism

CYP1A2-inhibitor:	0.036
CYP1A2-substrate:	0.772
CYP2C19-inhibitor:	0.061
CYP2C19-substrate:	0.063
CYP2C9-inhibitor:	0.047
CYP2C9-substrate:	0.851
CYP2D6-inhibitor:	0.015
CYP2D6-substrate:	0.464
CYP3A4-inhibitor:	0.014
CYP3A4-substrate:	0.139

ADMET: Excretion

Clearance (CL):	3.356
Half-life (T1/2):	0.857

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	0.235
Drug-inuced Liver Injury (DILI):	0.15
AMES Toxicity:	0.315
Rat Oral Acute Toxicity:	0.214
Maximum Recommended Daily Dose:	0.838
Skin Sensitization:	0.11
Carcinogencity:	0.77
Eye Corrosion:	0.003
Eye Irritation:	0.019
Respiratory Toxicity:	0.852

Download Data

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

Natural Product: NPC155230

Natural Product ID:	NPC155230
*Common Name:**	Sclerotiotide F
IUPAC Name:	(2E,4E)-6-oxo-N-[(3S,6S,9S)-3,4,7-trimethyl-2,5,8-trioxo-6-propan-2-yl-1,4,7-triazacyclododec-9-yl]hexa-2,4-dienamide
Synonyms:	sclerotiotide F
Standard InCHIKey:	KPPYRCDQUDIYQD-CAYKZORVSA-N
Standard InCHI:	InChI=1S/C21H32N4O5/c1-14(2)18-21(30)24(4)15(3)19(28)22-12-9-10-16(20(29)25(18)5)23-17(27)11-7-6-8-13-26/h6-8,11,13-16,18H,9-10,12H2,1-5H3,(H,22,28)(H,23,27)/b8-6+,11-7+/t15-,16-,18-/m0/s1
SMILES:	O=C/C=C/C=C/C(=N[C@H]1CCCN=C(O)[C@@H](N(C(=O)[C@@H](N(C1=O)C)C(C)C)C)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1164758
PubChem CID:	46850006
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000064] Macrolactams

*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
NPO33363	aspergillus sclerotiorum pt06-1	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20503985]

☑ 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
MIC	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	30000.0	nM	PMID[544004]

☑ 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 NPC155230 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	68
0.1-0.2	6577
0.2-0.3	27620
0.3-0.4	6759
0.4-0.5	1318
0.5-0.6	300
0.6-0.7	49
0.7-0.8	1
0.8-0.85	2
0.85-0.9	1
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9146	High Similarity	NPC284456
0.8916	High Similarity	NPC6902
0.8471	Intermediate Similarity	NPC184473
0.828	Intermediate Similarity	NPC469739
0.7158	Intermediate Similarity	NPC473495
0.6634	Remote Similarity	NPC38172
0.6549	Remote Similarity	NPC103391
0.6549	Remote Similarity	NPC472536
0.6455	Remote Similarity	NPC207820
0.6449	Remote Similarity	NPC475149
0.6449	Remote Similarity	NPC471097
0.6422	Remote Similarity	NPC476876
0.6415	Remote Similarity	NPC13175
0.6415	Remote Similarity	NPC475791
0.6383	Remote Similarity	NPC31756
0.6354	Remote Similarity	NPC84128
0.6354	Remote Similarity	NPC53858
0.6321	Remote Similarity	NPC475758
0.6316	Remote Similarity	NPC476243
0.6316	Remote Similarity	NPC476156
0.6316	Remote Similarity	NPC476137
0.6316	Remote Similarity	NPC476117
0.6306	Remote Similarity	NPC171734
0.625	Remote Similarity	NPC23984
0.625	Remote Similarity	NPC476302
0.6239	Remote Similarity	NPC239357
0.6239	Remote Similarity	NPC476877
0.6224	Remote Similarity	NPC472351
0.6195	Remote Similarity	NPC251122
0.614	Remote Similarity	NPC476875
0.6122	Remote Similarity	NPC235078
0.6117	Remote Similarity	NPC474576
0.6083	Remote Similarity	NPC315188
0.6068	Remote Similarity	NPC296043
0.6058	Remote Similarity	NPC62263
0.6058	Remote Similarity	NPC471098
0.6058	Remote Similarity	NPC173763
0.6042	Remote Similarity	NPC312315
0.6036	Remote Similarity	NPC205176
0.6022	Remote Similarity	NPC266888
0.6022	Remote Similarity	NPC209156
0.6022	Remote Similarity	NPC256312
0.6022	Remote Similarity	NPC161774
0.6019	Remote Similarity	NPC475801
0.6019	Remote Similarity	NPC474593
0.6017	Remote Similarity	NPC329216
0.6	Remote Similarity	NPC475975
0.5978	Remote Similarity	NPC214532
0.5978	Remote Similarity	NPC196007
0.5978	Remote Similarity	NPC76297
0.595	Remote Similarity	NPC160688
0.5941	Remote Similarity	NPC477539
0.5918	Remote Similarity	NPC470783
0.5872	Remote Similarity	NPC220234
0.5868	Remote Similarity	NPC470652
0.5849	Remote Similarity	NPC301010
0.5833	Remote Similarity	NPC473597
0.5806	Remote Similarity	NPC470654
0.5806	Remote Similarity	NPC470650
0.5806	Remote Similarity	NPC470653
0.5794	Remote Similarity	NPC280066
0.5773	Remote Similarity	NPC191774
0.5769	Remote Similarity	NPC320057
0.5766	Remote Similarity	NPC188785
0.5739	Remote Similarity	NPC474099
0.5727	Remote Similarity	NPC475440
0.5726	Remote Similarity	NPC50520
0.5714	Remote Similarity	NPC5864
0.5714	Remote Similarity	NPC124554
0.5714	Remote Similarity	NPC301148
0.57	Remote Similarity	NPC277341
0.57	Remote Similarity	NPC246005
0.57	Remote Similarity	NPC226982
0.5699	Remote Similarity	NPC471022
0.5688	Remote Similarity	NPC144780
0.5676	Remote Similarity	NPC26597
0.5667	Remote Similarity	NPC473819
0.5664	Remote Similarity	NPC198344
0.566	Remote Similarity	NPC477538
0.5656	Remote Similarity	NPC470545
0.5656	Remote Similarity	NPC469899
0.5648	Remote Similarity	NPC313265
0.5645	Remote Similarity	NPC273185
0.5638	Remote Similarity	NPC97614
0.5635	Remote Similarity	NPC6975
0.5614	Remote Similarity	NPC323720
0.5614	Remote Similarity	NPC128303
0.5614	Remote Similarity	NPC124549
0.561	Remote Similarity	NPC470546
0.56	Remote Similarity	NPC475542

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 NPC155230 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	70
0.1-0.2	761
0.2-0.3	5306
0.3-0.4	2573
0.4-0.5	392
0.5-0.6	46
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
0.6596	Remote Similarity	NPD7762	Phase 2
0.6596	Remote Similarity	NPD7763	Phase 2
0.602	Remote Similarity	NPD2683	Discontinued
0.5941	Remote Similarity	NPD3723	Clinical (unspecified phase)
0.5941	Remote Similarity	NPD7760	Phase 2
0.5941	Remote Similarity	NPD7759	Phase 2
0.5825	Remote Similarity	NPD3177	Phase 3
0.581	Remote Similarity	NPD4261	Phase 1
0.5773	Remote Similarity	NPD4278	Clinical (unspecified phase)
0.5741	Remote Similarity	NPD7841	Clinical (unspecified phase)
0.5636	Remote Similarity	NPD8038	Phase 2

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