NPASS Compound

Natural Product: NPC145149

Natural Product ID	NPC145149
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Purealdin L
IUPAC Name	(5S,6R)-7,9-dibromo-N-[4-(diaminomethylideneamino)butyl]-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms	Purealdin L
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL550970
PubChem CID	10391052
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002490] Azolines [CHEMONTID:0002211] Isoxazolines

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 47 48 0 0 0 0 0 0 0 0999 V2000 6.9913 -1.4478 1.0376 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8916 -0.5151 -0.0473 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6206 -0.1614 -0.5389 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0677 0.9915 -0.2077 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0909 2.1345 0.9671 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.7361 1.4364 -0.6829 C 0 0 1 0 0 0 0 0 0 0 0 0 3.0443 0.4800 -1.5761 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7242 -0.7649 -1.8893 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9084 -1.0739 -1.4203 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7712 -2.7338 -1.8613 Br 0 0 0 0 0 0 0 0 0 0 0 0 2.6480 1.1547 -2.7651 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4390 1.7146 -2.5280 N 0 0 0 0 0 0 0 0 0 0 0 0 0.8219 1.1750 -1.5271 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6839 0.0945 -0.9699 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4776 1.5357 -1.0153 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1090 2.4733 -1.5794 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0075 0.8317 0.1008 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3084 1.2285 0.5750 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6894 0.3736 1.7495 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0385 0.7882 2.2475 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0743 0.6245 1.1716 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1725 -0.7506 0.7167 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.1007 -1.0833 -0.2962 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6079 -0.1106 -0.9713 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.4705 -2.4489 -0.5700 N 0 0 0 0 0 0 0 0 0 0 0 0 2.9708 1.6796 0.4875 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0596 -1.5713 1.2495 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4380 -2.3636 0.8357 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5621 -0.8920 1.9213 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8650 2.4239 -1.1954 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2230 -1.4680 -2.5428 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3627 -0.8975 -1.3206 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7257 0.1018 0.1265 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5032 0.0633 0.5723 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0806 1.0463 -0.2233 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2478 2.3035 0.8290 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9708 0.5179 2.6102 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6763 -0.7043 1.5107 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9720 1.8913 2.4810 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3141 0.2916 3.1788 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0664 0.8176 1.6870 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9942 1.3426 0.3494 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5665 -1.4695 1.1353 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2930 -0.3426 -1.7204 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8731 -3.2403 -0.3161 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4041 -2.5820 -1.0528 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3725 1.2675 1.2773 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 7 11 1 6 11 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 2 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 3 23 25 1 0 6 26 1 0 9 3 1 0 14 7 1 0 1 27 1 0 1 28 1 0 1 29 1 0 6 30 1 6 8 31 1 0 14 32 1 0 14 33 1 0 17 34 1 0 18 35 1 0 18 36 1 0 19 37 1 0 19 38 1 0 20 39 1 0 20 40 1 0 21 41 1 0 21 42 1 0 22 43 1 0 24 44 1 0 25 45 1 0 25 46 1 0 26 47 1 0 M END

Standard InCHIKey	VJEGSWJGTALRBW-SWLSCSKDSA-N
Standard InCHI	InChI=1S/C15H21Br2N5O4/c1-25-11-8(16)6-15(12(23)10(11)17)7-9(22-26-15)13(24)20-4-2-3-5-21-14(18)19/h6,12,23H,2-5,7H2,1H3,(H,20,24)(H4,18,19,21)/t12-,15+/m0/s1
SMILES	COC1=C(Br)[C@@H]([C@]2(C=C1Br)ON=C(C2)C(=O)NCCCCNC(=N)N)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	493.0	Volume:	366.413 ? Van der Waals volume.
Dense:	1.345	LogP:	0.074 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.607 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.756 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	13.0
TPSA:	142.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	6.0	Rings:	2.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.201	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.531	Fsp³:	0.533
MCE-18:	52.174 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.562	Fluc inhibitor:	0.02 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.027 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.502 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.035	Promiscuous compounds:	0.028

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.77	MDCK Permeability:	-4.848
Pgp-inhibitor:	0.015	Pgp-substrate:	1.0
PAMPA:	0.884 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.42
20% Bioavailability (F20%):	0.885	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.157	MRP1:	0.914
Plasma Protein Binding (PPB):	87.834%	Volume Distribution (VD):	0.025
Fu:	9.829% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.003
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.032
CYP2D6-inhibitor:	0.443	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.062
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.01
HLM stability:	0.079 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

1.341

Half-life (T1/2):

2.432

ADMET: Toxicity

hERG Blockers:	0.239	hERG Blockers (10um):	0.312
Human Hepatotoxicity (H-HT):	0.54	Drug-induced Liver Injury (DILI):	0.919
AMES Toxicity:	0.969	Rat Oral Acute Toxicity:	0.905
Maximum Recommended Daily Dose:	0.815	Skin Sensitization:	1.0
Carcinogencity:	0.95	Eye Corrosion:	0.0
Eye Irritation:	0.055	Respiratory Toxicity:	0.991
Drug-induced Neurotoxicity:	0.266	Ototoxicity:	0.589
Hematotoxicity:	0.023	Drug-induced Nephrotoxicity:	0.92
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.02
A549 Cytotoxicity:	0.026	Hek293 Cytotoxicity:	0.35
BCF:	0.79 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.584 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.215 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.404 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	red sea	n.a.	PMID[18656986]
NPO13261	Suberea clavata	Species	Aplysinellidae	Eukaryota	n.a.	Australian	n.a.	PMID[19379003]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[21542602]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21542602]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13261	Suberea clavata	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13261	Suberea clavata	Species	Aplysinellidae	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	Organism Name	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
Inhibition	2
IZ	1

Activity Type	# Activity
Individual protein	2
Organism	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4197	Individual protein	Coagulation factor XI	Homo sapiens	Inhibition	=	12.0	%	PMID[19379003]
NPT4655	Individual protein	Coagulation factor IX	Homo sapiens	Inhibition	<	5.0	%	PMID[19379003]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	5.0	mm	PMID[21542602]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC145149 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	30194
0.1-0.2	19512
0.2-0.3	95
0.3-0.4	4
0.4-0.5	18
0.5-0.6	22
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9077	High Similarity	NPC260270
0.7742	Intermediate Similarity	NPC1702
0.75	Intermediate Similarity	NPC158672
0.6912	Remote Similarity	NPC487917
0.6667	Remote Similarity	NPC473262
0.6667	Remote Similarity	NPC202166
0.6486	Remote Similarity	NPC473261
0.6486	Remote Similarity	NPC300912
0.6286	Remote Similarity	NPC45830
0.6234	Remote Similarity	NPC470886
0.6154	Remote Similarity	NPC66855
0.6076	Remote Similarity	NPC130714
0.5974	Remote Similarity	NPC313173
0.5955	Remote Similarity	NPC607100
0.5873	Remote Similarity	NPC30521
0.575	Remote Similarity	NPC181086
0.5732	Remote Similarity	NPC477220
0.5676	Remote Similarity	NPC243106
0.5542	Remote Similarity	NPC608121
0.55	Remote Similarity	NPC81079
0.55	Remote Similarity	NPC304257
0.5432	Remote Similarity	NPC487872
0.5432	Remote Similarity	NPC600759
0.5432	Remote Similarity	NPC608122
0.5341	Remote Similarity	NPC601097
0.5301	Remote Similarity	NPC201900
0.5287	Remote Similarity	NPC483876
0.5287	Remote Similarity	NPC600925
0.5287	Remote Similarity	NPC607066
0.5238	Remote Similarity	NPC487873
0.5227	Remote Similarity	NPC202866
0.5172	Remote Similarity	NPC487915
0.5111	Remote Similarity	NPC77435
0.5111	Remote Similarity	NPC259071

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC145149 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7236
0.1-0.2	1891
0.2-0.3	23
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
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
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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