NPASS Compound

Natural Product: NPC300912

Natural Product ID	NPC300912
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Aplysinone A
IUPAC Name	(5S,6R)-7,9-dibromo-N-[5-[[(5S,6R,7S)-7,9-dibromo-6-hydroxy-8-oxo-1-oxa-2-azaspiro[4.5]deca-2,9-diene-3-carbonyl]amino]pentyl]-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL274349
PubChem CID	44424473
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones [CHEMONTID:0003487] Cyclic ketones [CHEMONTID:0004325] Cyclohexenones

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 66 69 0 0 0 0 0 0 0 0999 V2000 10.1540 1.0522 1.2115 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2120 0.1241 0.1701 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0910 -0.0871 -0.6090 C 0 0 0 0 0 0 0 0 0 0 0 0 8.9155 0.4133 -1.8163 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7389 0.2114 -2.6743 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7172 -0.6382 -2.0460 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9454 -1.1721 -0.7144 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0349 -0.9316 -0.0294 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2552 -1.6781 1.7272 Br 0 0 0 0 0 0 0 0 0 0 0 0 5.3422 0.0666 -1.9994 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4269 -1.0957 -2.0518 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0419 -2.0653 -2.6083 N 0 0 0 0 0 0 0 0 0 0 0 0 6.3356 -1.6998 -2.9653 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0363 -1.0943 -1.5336 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3304 -2.1313 -1.6208 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4992 0.0651 -0.9425 N 0 0 0 0 0 0 0 0 0 0 0 0 1.1500 0.1078 -0.4222 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9523 -0.8861 0.6780 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4412 -0.8942 1.2607 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7656 0.4436 1.8349 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1550 0.4901 2.4422 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1800 0.2050 1.4945 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.5406 0.2066 1.9024 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8614 0.4615 3.1143 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5997 -0.0855 0.9336 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4250 -0.3548 -0.3001 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.6185 -0.5812 -0.9408 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6702 -0.0972 -0.1373 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.9573 1.2905 -0.5067 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1406 1.8704 -0.4557 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2705 1.0739 0.0064 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.4563 1.4827 -0.0756 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9853 -0.2612 0.5896 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.8921 -0.9837 -0.2011 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.6851 -2.1931 0.4223 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.5769 -1.3339 0.7139 Br 0 0 0 0 0 0 0 0 0 0 0 0 -9.3944 3.6922 -0.9646 Br 0 0 0 0 0 0 0 0 0 0 0 0 -7.0504 -0.1149 1.2408 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1962 1.4452 -3.0883 O 0 0 0 0 0 0 0 0 0 0 0 0 10.3790 1.5016 -2.4517 Br 0 0 0 0 0 0 0 0 0 0 0 0 11.1697 1.0549 1.6988 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4519 0.7597 2.0216 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9397 2.0764 0.8705 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0882 -0.3026 -3.6134 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1897 -1.8147 -0.2222 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2044 0.7057 -2.8946 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2773 0.6185 -1.0497 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1375 0.9117 -0.8971 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8229 1.1193 -0.1772 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4944 -0.2118 -1.2865 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6225 -0.5671 1.5326 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3016 -1.8967 0.4229 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4350 -1.6929 2.0442 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1847 -1.2416 0.5096 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0122 0.6943 2.5829 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7480 1.2455 1.0705 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1418 -0.2762 3.2715 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3425 1.4565 2.9512 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9564 -0.0065 0.5018 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1353 1.9133 -0.8561 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5375 -0.0789 1.5989 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2096 -1.1518 -1.2295 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9750 -2.2204 1.3688 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3613 0.7752 1.8425 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2633 -1.0651 1.7913 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4901 2.1295 -2.4407 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 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 6 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 11 14 1 0 14 15 2 0 14 16 1 0 16 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 0 23 25 1 0 25 26 2 0 26 27 1 0 28 27 1 6 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 34 35 1 0 33 36 1 0 30 37 1 0 28 38 1 0 5 39 1 0 4 40 1 0 8 3 1 0 38 25 1 0 6 13 1 6 34 28 1 0 1 41 1 0 1 42 1 0 1 43 1 0 5 44 1 6 7 45 1 0 10 46 1 0 10 47 1 0 16 48 1 0 17 49 1 0 17 50 1 0 18 51 1 0 18 52 1 0 19 53 1 0 19 54 1 0 20 55 1 0 20 56 1 0 21 57 1 0 21 58 1 0 22 59 1 0 29 60 1 0 33 61 1 1 34 62 1 6 35 63 1 0 38 64 1 0 38 65 1 0 39 66 1 0 M END

Standard InCHIKey	KCVKPVRAUSPLPZ-CPXJRIKISA-N
Standard InCHI	InChI=1S/C24H26Br4N4O8/c1-38-18-12(26)8-24(20(35)16(18)28)10-14(32-40-24)22(37)30-6-4-2-3-5-29-21(36)13-9-23(39-31-13)7-11(25)17(33)15(27)19(23)34/h7-8,15,19-20,34-35H,2-6,9-10H2,1H3,(H,29,36)(H,30,37)/t15-,19+,20+,23-,24-/m1/s1
SMILES	COC1=C([C@@H]([C@@]2(C=C1Br)CC(=NO2)C(=O)NCCCCCNC(=O)C1=NO[C@]2(C=C(C(=O)[C@H]([C@@H]2O)Br)Br)C1)O)Br

Calculated Properties

Physi-Chem Properties

Molecular Weight:	813.85	Volume:	559.786 ? Van der Waals volume.
Dense:	1.454	LogP:	2.705 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.743 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.734 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	25.0
TPSA:	168.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	16.0

MedChem Properties

QED Drug-Likeness Score:	0.203	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.798	Fsp³:	0.542
MCE-18:	101.351 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.839	Fluc inhibitor:	0.021 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.145 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.508 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.364	Promiscuous compounds:	0.086

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.858	MDCK Permeability:	-4.648
Pgp-inhibitor:	0.009	Pgp-substrate:	0.042
PAMPA:	0.996 ? 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):	0.015
20% Bioavailability (F20%):	0.096	30% Bioavailability (F30%):	0.735
50% Bioavailability (F50%):	0.849

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.088	MRP1:	0.983
Plasma Protein Binding (PPB):	95.906%	Volume Distribution (VD):	-0.138
Fu:	2.274% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.0
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.409
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.565
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.991
HLM stability:	0.988 ? 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):

0.782

Half-life (T1/2):

4.006

ADMET: Toxicity

hERG Blockers:	0.015	hERG Blockers (10um):	0.081
Human Hepatotoxicity (H-HT):	0.44	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.999	Rat Oral Acute Toxicity:	0.994
Maximum Recommended Daily Dose:	0.996	Skin Sensitization:	1.0
Carcinogencity:	0.99	Eye Corrosion:	0.0
Eye Irritation:	0.176	Respiratory Toxicity:	0.974
Drug-induced Neurotoxicity:	0.672	Ototoxicity:	0.643
Hematotoxicity:	0.063	Drug-induced Nephrotoxicity:	0.926
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.116
A549 Cytotoxicity:	0.456	Hek293 Cytotoxicity:	0.908
BCF:	1.086 ? 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:	4.223 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.72 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.358 ? 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
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17512741]
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	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
GI50	3
TGI	3

Activity Type	# Activity
Cell line	6

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell line	MDA-MB-231	Homo sapiens	GI50	=	3300.0	nM	PMID[18479163]
NPT82	Cell line	MDA-MB-231	Homo sapiens	TGI	=	5400.0	nM	PMID[18479163]
NPT81	Cell line	A549	Homo sapiens	GI50	=	4500.0	nM	PMID[10514307]
NPT81	Cell line	A549	Homo sapiens	TGI	=	7100.0	nM	PMID[10514307]
NPT139	Cell line	HT-29	Homo sapiens	GI50	=	2800.0	nM	PMID[10514307]
NPT139	Cell line	HT-29	Homo sapiens	TGI	=	4800.0	nM	PMID[8350085]

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 NPC300912 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	32598
0.1-0.2	17166
0.2-0.3	39
0.3-0.4	1
0.4-0.5	15
0.5-0.6	23
0.6-0.7	6
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473261
0.9355	High Similarity	NPC473262
0.9355	High Similarity	NPC202166
0.8361	Intermediate Similarity	NPC158672
0.8033	Intermediate Similarity	NPC470892
0.8033	Intermediate Similarity	NPC172626
0.7742	Intermediate Similarity	NPC1702
0.7606	Intermediate Similarity	NPC470886
0.6933	Remote Similarity	NPC130714
0.6757	Remote Similarity	NPC260270
0.6667	Remote Similarity	NPC487917
0.6486	Remote Similarity	NPC145149
0.6197	Remote Similarity	NPC473683
0.6154	Remote Similarity	NPC66855
0.5974	Remote Similarity	NPC313173
0.5949	Remote Similarity	NPC181086
0.5873	Remote Similarity	NPC30521
0.5696	Remote Similarity	NPC81079
0.5696	Remote Similarity	NPC304257
0.5542	Remote Similarity	NPC477220
0.5542	Remote Similarity	NPC608121
0.5465	Remote Similarity	NPC483876
0.5465	Remote Similarity	NPC600925
0.5465	Remote Similarity	NPC607066
0.5432	Remote Similarity	NPC487872
0.5432	Remote Similarity	NPC600759
0.5432	Remote Similarity	NPC608122
0.5402	Remote Similarity	NPC202866
0.5341	Remote Similarity	NPC601097
0.5316	Remote Similarity	NPC289324
0.5301	Remote Similarity	NPC201900
0.5281	Remote Similarity	NPC77435
0.5281	Remote Similarity	NPC259071
0.5275	Remote Similarity	NPC480151
0.5238	Remote Similarity	NPC487873
0.5165	Remote Similarity	NPC603425
0.5054	Remote Similarity	NPC606574

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC300912 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7360
0.1-0.2	1790
0.2-0.3	0
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