NPASS Compound

Natural Product: NPC475706

Natural Product ID	NPC475706
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(5Z)-4-Hydroxy-5-[(2R,5Z,9Z)-13-(2-Hydroxy-5-Oxo-2H-Furan-3-Yl)-2,6,10-Trimethyltrideca-5,9-Dienylidene]-3-Methylfuran-2-One
IUPAC Name	(5Z)-4-hydroxy-5-[(2R,5Z,9Z)-13-(2-hydroxy-5-oxo-2H-furan-3-yl)-2,6,10-trimethyltrideca-5,9-dienylidene]-3-methylfuran-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL512286
PubChem CID	54729898
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001538] Diterpene lactones

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 65 66 0 0 0 0 0 0 0 0999 V2000 8.9798 -3.2906 -0.2993 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0434 -2.1079 -0.2596 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7312 -2.1277 -0.3664 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1710 -0.7676 -0.2794 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8955 -0.4295 -0.3485 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4715 0.9735 -0.2465 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6280 1.9554 -0.2617 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5620 1.1995 0.9244 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3215 0.3441 0.7731 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3806 0.5341 1.8918 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1692 0.9963 1.7733 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6756 1.1301 3.0294 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4361 1.4112 0.5082 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6858 0.5386 0.2531 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2511 0.9935 -1.0206 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4435 1.5076 -1.1352 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8868 1.9285 -2.5187 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3574 1.7184 -0.0168 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6523 0.9310 -0.1829 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3364 -0.5535 -0.2667 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5939 -1.3137 -0.4372 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8623 -2.0945 -1.4744 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1861 -2.6657 -1.2804 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8036 -3.4564 -2.0397 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6792 -2.1882 -0.0893 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7493 -1.3213 0.5174 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2766 -0.0333 0.6248 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2823 0.0432 -0.1118 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4316 -0.7194 -0.0938 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5964 -0.2780 0.0422 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9626 -3.2546 -0.5372 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4090 -4.1545 0.0961 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9064 -3.0870 0.2350 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1906 -3.5108 -1.3659 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1660 -1.1976 -0.4874 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8563 1.2756 -1.1572 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1973 1.7789 -1.1958 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1695 2.9684 -0.3489 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2292 1.9606 0.6440 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3362 2.2569 1.1051 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0992 0.7866 1.8265 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6993 -0.7353 0.7838 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8129 0.4371 -0.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7911 0.2448 2.8821 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4205 1.9357 2.9066 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2020 0.1976 3.2336 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0021 1.3297 3.8813 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1730 1.3602 -0.3893 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7942 2.4801 0.5671 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3196 -0.5229 0.1896 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3944 0.5871 1.0594 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6458 0.9049 -1.9575 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4991 2.9620 -2.7462 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9816 1.9906 -2.5942 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4389 1.2416 -3.2571 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7046 2.8108 -0.1185 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9382 1.6650 0.9898 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1423 1.2448 -1.1079 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2669 1.1041 0.7339 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7882 -0.8830 0.6528 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6835 -0.7632 -1.1302 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2420 -2.3007 -2.3323 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3864 -1.6790 1.4893 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2547 -0.1168 0.6895 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3186 -4.1754 -0.6703 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 3 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 3 11 12 1 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 3 16 17 1 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 1 0 4 28 1 0 28 29 1 0 29 30 2 0 3 31 1 0 29 2 1 0 26 21 1 0 1 32 1 0 1 33 1 0 1 34 1 0 5 35 1 0 6 36 1 0 7 37 1 0 7 38 1 0 7 39 1 0 8 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 10 44 1 0 12 45 1 0 12 46 1 0 12 47 1 0 13 48 1 0 13 49 1 0 14 50 1 0 14 51 1 0 15 52 1 0 17 53 1 0 17 54 1 0 17 55 1 0 18 56 1 0 18 57 1 0 19 58 1 0 19 59 1 0 20 60 1 0 20 61 1 0 22 62 1 0 26 63 1 0 27 64 1 0 31 65 1 0 M END

Standard InCHIKey	JMHINFUUTXGQEY-OKJDYQSWSA-N
Standard InCHI	InChI=1S/C25H34O6/c1-16(10-6-12-18(3)14-21-23(27)19(4)24(28)30-21)8-5-9-17(2)11-7-13-20-15-22(26)31-25(20)29/h9-10,14-15,18,25,27,29H,5-8,11-13H2,1-4H3/b16-10-,17-9-,21-14-/t18-,25?/m1/s1
SMILES	CC1=C(C(=CC(C)CCC=C(C)CCC=C(C)CCCC2=CC(=O)OC2O)OC1=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.24	Volume:	458.129 ? Van der Waals volume.
Dense:	0.939	LogP:	5.857 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.394 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.806 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	15.0
TPSA:	93.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.34	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.349	Fsp³:	0.52
MCE-18:	32.842 ? 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:	0.727	Fluc inhibitor:	0.141 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.088 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.438 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.533	Promiscuous compounds:	0.003

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.927	MDCK Permeability:	-4.883
Pgp-inhibitor:	0.28	Pgp-substrate:	0.02
PAMPA:	0.43 ? 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):	0.127
20% Bioavailability (F20%):	0.047	30% Bioavailability (F30%):	0.436
50% Bioavailability (F50%):	0.623

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.129	MRP1:	0.992
Plasma Protein Binding (PPB):	98.212%	Volume Distribution (VD):	-0.279
Fu:	1.531% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.915
OATP1B3 inhibitor:	0.886	BCRP inhibitor:	0.001
BSEP inhibitor:	0.981

ADMET: Metabolism

CYP1A2-inhibitor:	0.127	CYP1A2-substrate:	0.354
CYP2C19-inhibitor:	0.911	CYP2C19-substrate:	0.158
CYP2C9-inhibitor:	0.959	CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.009	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.704	CYP2C8-inhibitor:	0.202
HLM stability:	0.999 ? 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):

4.7

Half-life (T1/2):

1.117

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.209
Human Hepatotoxicity (H-HT):	0.568	Drug-induced Liver Injury (DILI):	0.425
AMES Toxicity:	0.218	Rat Oral Acute Toxicity:	0.246
Maximum Recommended Daily Dose:	0.664	Skin Sensitization:	1.0
Carcinogencity:	0.416	Eye Corrosion:	0.026
Eye Irritation:	0.808	Respiratory Toxicity:	0.292
Drug-induced Neurotoxicity:	0.08	Ototoxicity:	0.691
Hematotoxicity:	0.302	Drug-induced Nephrotoxicity:	0.9
Genotoxicity:	0.171	RPMI-8226 Immunitoxicity:	0.074
A549 Cytotoxicity:	0.007	Hek293 Cytotoxicity:	0.066
BCF:	1.503 ? 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:	4.953 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.534 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.757 ? 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
NPO33064	sarcotragus sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11678655]
NPO33064	sarcotragus sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12350153]
NPO33064	sarcotragus sp.	Species	Irciniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18341287]

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
IC50	1
MIC	9

Activity Type	# Activity
Individual protein	1
Organism	9

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1087	Individual protein	Isocitrate lyase	Candida albicans	IC50	=	39.4	ug.mL-1	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT729	Organism	Micrococcus luteus	Micrococcus luteus	MIC	=	50.0	ug.mL-1	PMID[17988097]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	>	100.0	ug.mL-1	PMID[19041248]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	>	100.0	ug.mL-1	PMID[2016706]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	100.0	ug.mL-1	PMID[15217281]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[25028062]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	>	100.0	ug.mL-1	PMID[19114678]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	100.0	ug.mL-1	PMID[15217281]

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 NPC475706 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	19158
0.1-0.2	28763
0.2-0.3	1811
0.3-0.4	89
0.4-0.5	23
0.5-0.6	11
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	Natural Product ID
0.7368	Intermediate Similarity	NPC475739
0.661	Remote Similarity	NPC474424
0.6349	Remote Similarity	NPC475714
0.5692	Remote Similarity	NPC474028
0.5652	Remote Similarity	NPC474136
0.5507	Remote Similarity	NPC71274
0.5507	Remote Similarity	NPC75557
0.5352	Remote Similarity	NPC26597
0.5352	Remote Similarity	NPC476351
0.5352	Remote Similarity	NPC283284
0.5352	Remote Similarity	NPC289911
0.5231	Remote Similarity	NPC475879
0.5152	Remote Similarity	NPC45409
0.5065	Remote Similarity	NPC489596

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475706 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6699
0.1-0.2	2418
0.2-0.3	29
0.3-0.4	4
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