NPASS Compound

Natural Product: NPC604728

Natural Product ID	NPC604728
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PEALHNTTZWPAQZ-JAQAVICVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL4102811
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 63 65 0 0 0 0 0 0 0 0999 V2000 3.8851 -1.0514 2.8300 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8988 -0.6856 1.5784 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8912 -1.1610 0.5903 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3309 -1.5295 -0.7282 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1481 -0.7562 -1.2056 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1913 -0.4597 -0.0522 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8519 0.0541 -0.4897 C 0 0 1 0 0 0 0 0 0 0 0 0 0.8096 0.3438 -1.9730 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2016 -0.9652 -0.1581 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5805 -0.7235 -0.4764 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4376 -0.1825 0.4804 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7669 0.1038 0.2554 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6257 0.6741 1.2906 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8360 0.9352 1.1019 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0927 0.9433 2.5394 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9273 1.4976 3.5433 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2746 -0.1656 -1.0013 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6151 0.1131 -1.2575 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4564 -0.7007 -1.9713 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9753 -0.9594 -3.2064 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5751 -2.1305 -3.6593 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1102 -0.9818 -1.7126 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4187 -1.5238 -2.7868 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4684 1.3684 0.1519 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7322 2.5701 -0.7389 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8855 1.5475 1.5600 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8867 0.6062 2.1092 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8895 0.2687 1.0362 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6938 1.4748 0.6178 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6678 -1.7580 3.1478 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1785 -0.7233 3.5746 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7446 -0.4262 0.4859 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3826 -2.0580 1.0509 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1468 -1.4306 -1.4938 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1245 -2.6416 -0.7189 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5722 -1.4844 -1.8560 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3495 0.0953 -1.8454 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0151 -1.5071 0.3575 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9909 -0.4986 -2.6259 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6023 1.0993 -2.2488 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1943 0.7578 -2.1907 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1662 -1.9429 -0.6346 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0456 -1.1953 0.9451 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1045 0.0492 1.4971 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7293 2.6039 3.5314 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0158 1.3897 3.2926 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7568 1.0595 4.5446 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2036 -0.7143 -1.4358 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0027 -1.9012 -4.6764 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4374 -2.4696 -3.0558 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8456 -2.9347 -3.8344 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9285 -2.4119 -2.6005 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6661 1.3788 0.1743 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5149 3.4600 -0.0706 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7534 2.7019 -1.0636 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0152 2.6708 -1.5509 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0261 1.5658 2.2959 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2928 2.5988 1.6488 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4943 -0.3358 2.5188 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4667 1.1552 2.9114 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6073 1.5164 1.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1760 2.4297 0.8355 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0037 1.3769 -0.4198 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 6 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 1 0 12 17 2 0 17 18 1 0 17 19 1 0 19 20 1 0 20 21 1 0 19 22 2 0 22 23 1 0 7 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 27 28 1 0 28 29 1 6 28 2 1 0 28 6 1 0 22 10 1 0 1 30 1 0 1 31 1 0 3 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 6 38 1 1 8 39 1 0 8 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 11 44 1 0 16 45 1 0 16 46 1 0 16 47 1 0 18 48 1 0 21 49 1 0 21 50 1 0 21 51 1 0 23 52 1 0 24 53 1 1 25 54 1 0 25 55 1 0 25 56 1 0 26 57 1 0 26 58 1 0 27 59 1 0 27 60 1 0 29 61 1 0 29 62 1 0 29 63 1 0 M END

Standard InCHIKey	PEALHNTTZWPAQZ-JAQAVICVSA-N
Standard InCHI	InChI=1S/C24H34O5/c1-14-8-7-9-18-23(14,3)11-10-15(2)24(18,4)13-16-12-17(22(27)29-6)20(26)21(28-5)19(16)25/h12,15,18,25-26H,1,7-11,13H2,2-6H3/t15-,18+,23+,24+/m1/s1
SMILES	C=C1CCC[C@@H]2[C@@](C)(Cc3cc(C(=O)OC)c(O)c(OC)c3O)[C@H](C)CC[C@@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	402.24	Volume:	428.76 ? Van der Waals volume.
Dense:	0.938	LogP:	4.579 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.737 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.95 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	19.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.532	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.171	Fsp³:	0.625
MCE-18:	83.077 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.379	Fluc inhibitor:	0.324 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.284 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.319	Promiscuous compounds:	0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.112	MDCK Permeability:	-4.75
Pgp-inhibitor:	0.984	Pgp-substrate:	0.0
PAMPA:	0.109 ? 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):	0.0
20% Bioavailability (F20%):	0.149	30% Bioavailability (F30%):	0.351
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.296	MRP1:	0.992
Plasma Protein Binding (PPB):	97.836%	Volume Distribution (VD):	-0.267
Fu:	1.901% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.992
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.995	CYP1A2-substrate:	0.231
CYP2C19-inhibitor:	0.437	CYP2C19-substrate:	0.604
CYP2C9-inhibitor:	0.125	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.532	CYP2D6-substrate:	0.051
CYP3A4-inhibitor:	0.944	CYP3A4-substrate:	0.974
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.993 ? 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):

7.297

Half-life (T1/2):

0.58

ADMET: Toxicity

hERG Blockers:	0.046	hERG Blockers (10um):	0.222
Human Hepatotoxicity (H-HT):	0.589	Drug-induced Liver Injury (DILI):	0.663
AMES Toxicity:	0.362	Rat Oral Acute Toxicity:	0.326
Maximum Recommended Daily Dose:	0.637	Skin Sensitization:	0.721
Carcinogencity:	0.709	Eye Corrosion:	0.049
Eye Irritation:	0.939	Respiratory Toxicity:	0.641
Drug-induced Neurotoxicity:	0.149	Ototoxicity:	0.384
Hematotoxicity:	0.441	Drug-induced Nephrotoxicity:	0.65
Genotoxicity:	0.28	RPMI-8226 Immunitoxicity:	0.061
A549 Cytotoxicity:	0.209	Hek293 Cytotoxicity:	0.227
BCF:	1.891 ? 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:	4.735 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.868 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.5 ? 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
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	Tongoa, Vanuatu Islands	1996	PMID[10757711]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12662110]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497946]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	Tong-Yong City in the South Sea, Korea	n.a.	PMID[16905319]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17567172]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17988093]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18407692]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[24992702]
NPO33376	Spongia sp.	Species	Spongiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
MIC	4
IC50	4

Activity Type	# Activity
Cell line	4
Organism	4

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
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	50000.0	nM	PMID[28558970]
NPT165	Cell line	HeLa	Homo sapiens	IC50	>	50000.0	nM	PMID[28558970]
NPT1374	Cell line	WI-38	Homo sapiens	IC50	>	50000.0	nM	PMID[28558970]
NPT81	Cell line	A549	Homo sapiens	IC50	>	50000.0	nM	PMID[28558970]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MIC	>	100000.0	nM	PMID[28558970]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	12500.0	nM	PMID[28558970]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100000.0	nM	PMID[28558970]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	100000.0	nM	PMID[28558970]

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 NPC604728 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	7038
0.1-0.2	40782
0.2-0.3	1956
0.3-0.4	48
0.4-0.5	14
0.5-0.6	6
0.6-0.7	6
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8125	Intermediate Similarity	NPC600783
0.8125	Intermediate Similarity	NPC606128
0.8125	Intermediate Similarity	NPC610813
0.75	Intermediate Similarity	NPC481272
0.7424	Intermediate Similarity	NPC124842
0.7083	Intermediate Similarity	NPC481273
0.6567	Remote Similarity	NPC75295
0.6471	Remote Similarity	NPC290286
0.6269	Remote Similarity	NPC489119
0.6027	Remote Similarity	NPC62051
0.6027	Remote Similarity	NPC606953
0.6027	Remote Similarity	NPC611058
0.5676	Remote Similarity	NPC475848
0.5634	Remote Similarity	NPC176590
0.5467	Remote Similarity	NPC474306
0.5373	Remote Similarity	NPC77772
0.5373	Remote Similarity	NPC53548
0.5205	Remote Similarity	NPC489114

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC604728 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3421
0.1-0.2	5686
0.2-0.3	43
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