NPASS Compound

Structure

NPC475455 OpenBabel07101719182D 55 57 0 0 1 0 0 0 0 0999 V2000 -10.0776 0.2729 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1431 0.8966 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1868 1.3124 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5396 0.7772 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8923 0.2420 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4431 -3.1689 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2454 -5.6133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4456 -0.6615 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7024 0.0076 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4752 -3.6817 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1295 -0.1853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7612 -1.0055 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0160 -4.9323 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4303 -0.2624 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7830 -0.7976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1025 -4.5255 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8250 -4.3445 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7175 -1.4213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8267 -0.3818 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5540 -1.2443 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5115 -1.3609 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2935 -6.1133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4084 -0.4703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4740 0.1534 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4958 0.3614 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8486 -0.1739 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2013 -0.7091 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5295 -2.7622 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2454 -5.6133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2935 -5.1133 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5322 -1.4522 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7205 -3.3500 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.1151 -1.9875 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.4250 -1.7677 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.0483 -2.1645 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1794 -0.9170 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0933 -1.7796 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5000 -0.8660 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4945 -0.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7024 -1.9487 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.0702 -1.9566 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3424 -4.8043 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.8412 -2.4033 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3573 -3.1155 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4885 -1.8681 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1939 -2.9385 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2340 -1.1799 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3424 -6.4223 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8070 -2.9432 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8364 -2.4487 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 P 0 0 0 0 0 0 0 0 0 0 0 0 1 23 1 0 0 0 0 2 24 1 0 0 0 0 3 25 1 0 0 0 0 7 29 1 0 0 0 0 8 39 1 0 0 0 0 9 39 1 0 0 0 0 10 49 1 0 0 0 0 11 50 1 0 0 0 0 12 14 1 0 0 0 0 12 15 1 0 0 0 0 13 16 2 0 0 0 0 13 17 1 0 0 0 0 14 23 1 0 0 0 0 15 24 2 0 0 0 0 16 30 1 0 0 0 0 18 23 2 0 0 0 0 18 35 1 0 0 0 0 19 25 2 0 0 0 0 19 26 1 0 0 0 0 20 31 1 0 0 0 0 21 34 1 0 0 0 0 22 30 2 0 0 0 0 22 51 1 0 0 0 0 24 25 1 0 0 0 0 26 4 1 1 0 0 0 26 36 1 0 0 0 0 27 5 1 1 0 0 0 27 31 1 0 0 0 0 27 36 1 0 0 0 0 28 6 1 6 0 0 0 28 32 1 0 0 0 0 28 34 1 0 0 0 0 29 42 2 0 0 0 0 29 51 1 0 0 0 0 30 42 1 0 0 0 0 31 43 1 6 0 0 0 32 17 1 1 0 0 0 32 52 1 0 0 0 0 33 20 1 6 0 0 0 33 49 1 0 0 0 0 34 50 1 6 0 0 0 35 41 2 0 0 0 0 35 44 1 0 0 0 0 36 45 1 6 0 0 0 37 33 1 6 0 0 0 37 38 1 0 0 0 0 37 53 1 0 0 0 0 38 39 1 0 0 0 0 38 54 1 6 0 0 0 39 40 1 0 0 0 0 40 21 1 1 0 0 0 40 52 1 0 0 0 0 40 53 1 0 0 0 0 46 55 1 0 0 0 0 47 55 1 0 0 0 0 48 55 2 0 0 0 0 54 55 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	796.43
Volume:	803.575
LogP:	2.45
LogD:	1.225
LogS:	-4.128
# Rotatable Bonds:	19
TPSA:	210.1
# H-Bond Aceptor:	14
# H-Bond Donor:	5
# Rings:	3
# Heavy Atoms:	15

MedChem Properties

QED Drug-Likeness Score:	0.071
Synthetic Accessibility Score:	6.961
Fsp3:	0.7
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:	-5.284
MDCK Permeability:	4.7481989895459265e-06
Pgp-inhibitor:	0.977
Pgp-substrate:	0.99
Human Intestinal Absorption (HIA):	0.074
20% Bioavailability (F20%):	0.904
30% Bioavailability (F30%):	0.778

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007
Plasma Protein Binding (PPB):	81.15840911865234%
Volume Distribution (VD):	1.091
Pgp-substrate:	12.12419319152832%

ADMET: Metabolism

CYP1A2-inhibitor:	0.004
CYP1A2-substrate:	0.11
CYP2C19-inhibitor:	0.017
CYP2C19-substrate:	0.068
CYP2C9-inhibitor:	0.012
CYP2C9-substrate:	0.011
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.059
CYP3A4-inhibitor:	0.053
CYP3A4-substrate:	0.299

ADMET: Excretion

Clearance (CL):	3.641
Half-life (T1/2):	0.859

ADMET: Toxicity

hERG Blockers:	0.949
Human Hepatotoxicity (H-HT):	0.737
Drug-inuced Liver Injury (DILI):	0.467
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.765
Maximum Recommended Daily Dose:	0.478
Skin Sensitization:	0.673
Carcinogencity:	0.745
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.948

Download Data

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

Natural Product: NPC475455

Natural Product ID:	NPC475455
*Common Name:**	Swinhoeiamide A
IUPAC Name:	[(2R,3R,5R,7S,8S,9R)-2-[(1R,3S,4S,5R,6R,7E,9E,13Z)-15-amino-3,5-dihydroxy-1-methoxy-4,6,8,9,13-pentamethyl-15-oxopentadeca-7,9,13-trienyl]-7-methoxy-4,4,8-trimethyl-9-[(E)-3-(2-methyl-1,3-oxazol-4-yl)prop-2-enyl]-1,10-dioxaspiro[4.5]decan-3-yl] dihydrogen phosphate
Synonyms:
Standard InCHIKey:	NWFMVMFBNZSIHF-PKGIXKDLSA-N
Standard InCHI:	InChI=1S/C40H65N2O12P/c1-23(18-35(41)44)14-12-15-24(2)25(3)19-26(4)36(45)27(5)31(43)20-33(49-10)37-38(54-55(46,47)48)39(8,9)40(53-37)21-34(50-11)28(6)32(52-40)17-13-16-30-22-51-29(7)42-30/h13,15-16,18-19,22,26-28,31-34,36-38,43,45H,12,14,17,20-21H2,1-11H3,(H2,41,44)(H2,46,47,48)/b16-13+,23-18-,24-15+,25-19+/t26-,27+,28-,31+,32-,33-,34+,36-,37-,38+,40-/m1/s1
SMILES:	CO[C@@H]([C@H]1O[C@@]2(C([C@H]1OP(=O)(O)O)(C)C)C[C@H](OC)[C@@H]([C@H](O2)C/C=C/c1coc(n1)C)C)C[C@@H]([C@@H]([C@@H]([C@@H](/C=C(/C(=C/CC/C(=CC(=N)O)/C)/C)C)C)O)C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL505968
PubChem CID:	643644
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001549] Monoterpenoids [CHEMONTID:0000051] Aromatic monoterpenoids

*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
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11421754]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12193024]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	Papua New Guinea	n.a.	PMID[15679329]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[16441091]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17125225]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18318032]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[19961178]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	palau	n.a.	PMID[20078073]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20078073]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21428459]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[23830699]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[27213234]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[27548648]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[29989811]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[30346758]
NPO22214	Theonella swinhoei	Species	Theonellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[32191460]
NPO22214	Theonella swinhoei	Species	Theonellidae	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
LD50	2
MIC	2
Others	2

Activity Type	# Activity
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	LC50	=	2.98	ppm	PMID[484658]
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	LD50	=	10.0	ug	PMID[484658]
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	LD50	=	0.98	ug	PMID[484658]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	1.2	ug.mL-1	PMID[484658]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	MIC	=	1.0	ug.mL-1	PMID[484658]
NPT985	Organism	Cladosporium cucumerinum	Cladosporium cucumerinum	IZ	=	14.0	mm	PMID[484658]

☑ 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 NPC475455 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	205
0.1-0.2	1055
0.2-0.3	3738
0.3-0.4	24784
0.4-0.5	12597
0.5-0.6	284
0.6-0.7	28
0.7-0.8	4
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.7778	Intermediate Similarity	NPC211555
0.7746	Intermediate Similarity	NPC12660
0.7719	Intermediate Similarity	NPC186452
0.7701	Intermediate Similarity	NPC54983
0.7072	Intermediate Similarity	NPC30527
0.6443	Remote Similarity	NPC314523
0.6443	Remote Similarity	NPC58001
0.6293	Remote Similarity	NPC476829
0.6018	Remote Similarity	NPC168135
0.6018	Remote Similarity	NPC322800
0.6018	Remote Similarity	NPC477218
0.5973	Remote Similarity	NPC299035
0.5973	Remote Similarity	NPC177432
0.5909	Remote Similarity	NPC309919
0.5909	Remote Similarity	NPC49195
0.5857	Remote Similarity	NPC295653
0.5857	Remote Similarity	NPC107458
0.5841	Remote Similarity	NPC325683
0.5841	Remote Similarity	NPC476832
0.5796	Remote Similarity	NPC37924
0.5752	Remote Similarity	NPC477219
0.5741	Remote Similarity	NPC258022
0.5729	Remote Similarity	NPC127775
0.5708	Remote Similarity	NPC477587
0.5708	Remote Similarity	NPC477589
0.5702	Remote Similarity	NPC476828
0.5699	Remote Similarity	NPC231110
0.5685	Remote Similarity	NPC97078
0.5685	Remote Similarity	NPC470146
0.5685	Remote Similarity	NPC101980
0.5681	Remote Similarity	NPC224395
0.5681	Remote Similarity	NPC208297
0.567	Remote Similarity	NPC312887
0.566	Remote Similarity	NPC477590
0.566	Remote Similarity	NPC477586
0.566	Remote Similarity	NPC477588
0.566	Remote Similarity	NPC477585
0.5654	Remote Similarity	NPC268063
0.5654	Remote Similarity	NPC224609
0.5648	Remote Similarity	NPC52587
0.5619	Remote Similarity	NPC103452
0.5619	Remote Similarity	NPC46313
0.5619	Remote Similarity	NPC199461
0.5614	Remote Similarity	NPC476830
0.5602	Remote Similarity	NPC252616
0.5602	Remote Similarity	NPC45576
0.5602	Remote Similarity	NPC154873
0.5602	Remote Similarity	NPC32583
0.5602	Remote Similarity	NPC109498
0.5602	Remote Similarity	NPC474090
0.5602	Remote Similarity	NPC61667
0.5602	Remote Similarity	NPC163147

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 NPC475455 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	144
0.1-0.2	476
0.2-0.3	1486
0.3-0.4	4828
0.4-0.5	2161
0.5-0.6	52
0.6-0.7	3
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
0.6667	Remote Similarity	NPD6347	Phase 2
0.655	Remote Similarity	NPD7490	Discontinued
0.6214	Remote Similarity	NPD7896	Approved
0.5991	Remote Similarity	NPD4667	Clinical (unspecified phase)
0.5782	Remote Similarity	NPD6857	Phase 3
0.56	Remote Similarity	NPD6974	Phase 3

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