NPASS Compound

Natural Product: NPC75557

Natural Product ID	NPC75557
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-((R,5Z,9Z)-13-(Furan-3-Yl)-2,6,10-Trimethyltrideca-5,9-Dienylidene)-4-Hydroxy-3-Methylfuran-2(5H)-One
IUPAC Name	(5Z)-5-[(2R,5Z,9Z)-13-(furan-3-yl)-2,6,10-trimethyltrideca-5,9-dienylidene]-4-hydroxy-3-methylfuran-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL467948
PubChem CID	54689639
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 63 64 0 0 0 0 0 0 0 0999 V2000 0.4051 -1.6179 1.6654 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1989 -1.0506 0.4032 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2613 -1.6554 -0.1663 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8913 -1.1552 -1.3924 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2597 -0.6458 -1.3350 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3953 -1.5785 -0.9703 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.2807 -2.2101 0.3645 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5985 -0.7378 -1.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4924 -0.4842 -0.2880 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7183 0.3589 -0.4764 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3672 0.3734 0.6693 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.6438 1.1166 0.8621 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6357 -0.4313 1.6518 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0162 -0.6017 2.8398 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5099 -0.9249 1.0151 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0270 0.9734 -1.6838 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4049 0.1662 -0.1379 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8509 -0.1748 -0.4822 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5755 0.9558 -1.0332 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6204 1.5098 -0.4719 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2414 2.6893 -1.2162 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1702 1.1056 0.8234 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5583 0.5702 0.8323 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6365 1.4742 0.3398 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9391 0.7122 0.4795 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5141 -0.1045 -0.4703 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6956 -0.5949 0.0806 C 0 0 0 0 0 0 0 0 0 0 0 0 9.8063 -0.0944 1.2834 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7853 0.6892 1.5654 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3925 -1.7108 2.4489 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1533 -0.9250 2.0943 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8860 -2.5823 1.4954 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5784 -2.5437 0.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1976 -0.4851 -1.9887 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9327 -2.0654 -2.1166 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5042 -0.2480 -2.3762 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3443 0.2193 -0.6115 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3948 -2.4215 -1.7232 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2897 -2.6353 0.6253 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8076 -1.6340 1.1510 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6852 -3.1612 0.2319 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7013 -0.3192 -2.1855 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1884 1.2200 -0.1001 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2942 0.6334 1.6243 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3772 2.1256 1.2433 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2417 1.3764 -2.1952 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1233 0.7095 -0.9035 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4782 0.9021 0.7340 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3291 -0.6520 0.3616 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7880 -0.9485 -1.3235 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2371 1.3966 -1.9966 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8160 3.3231 -0.5511 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7550 2.3819 -2.1171 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3520 3.2907 -1.5644 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5156 0.3796 1.3256 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1025 2.0340 1.4899 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5675 -0.4221 0.3299 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8182 0.3309 1.9071 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7024 2.4151 0.9152 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5412 1.7474 -0.7339 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1132 -0.3162 -1.4536 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3466 -1.2662 -0.4608 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6439 1.2184 2.4906 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 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 13 15 1 0 10 16 1 0 2 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 15 9 1 0 29 25 2 0 1 30 1 0 1 31 1 0 1 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 6 7 39 1 0 7 40 1 0 7 41 1 0 8 42 1 0 12 43 1 0 12 44 1 0 12 45 1 0 16 46 1 0 17 47 1 0 17 48 1 0 18 49 1 0 18 50 1 0 19 51 1 0 21 52 1 0 21 53 1 0 21 54 1 0 22 55 1 0 22 56 1 0 23 57 1 0 23 58 1 0 24 59 1 0 24 60 1 0 26 61 1 0 27 62 1 0 29 63 1 0 M END

Standard InCHIKey	IBYNQQZMPJJRJJ-KLURGBKRSA-N
Standard InCHI	InChI=1S/C25H34O4/c1-18(8-5-9-19(2)11-7-13-22-14-15-28-17-22)10-6-12-20(3)16-23-24(26)21(4)25(27)29-23/h9-10,14-17,20,26H,5-8,11-13H2,1-4H3/b18-10-,19-9-,23-16-/t20-/m1/s1
SMILES	C/C(=C/CC[C@@H](C)/C=C1/C(=C(C)C(=O)O1)O)/CC/C=C(/C)CCCc1ccoc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	398.25	Volume:	440.549 ? Van der Waals volume.
Dense:	0.904	LogP:	7.249 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.317 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.386 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	14.0
TPSA:	59.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.323	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.83	Fsp³:	0.48
MCE-18:	42.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.961	Fluc inhibitor:	0.371 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.046 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.301 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.446	Promiscuous compounds:	0.059

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.801	MDCK Permeability:	-4.693
Pgp-inhibitor:	0.832	Pgp-substrate:	0.001
PAMPA:	0.002 ? 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):	0.1
20% Bioavailability (F20%):	0.431	30% Bioavailability (F30%):	0.877
50% Bioavailability (F50%):	0.702

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.113	MRP1:	0.994
Plasma Protein Binding (PPB):	98.01%	Volume Distribution (VD):	0.047
Fu:	1.885% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.126
OATP1B3 inhibitor:	0.161	BCRP inhibitor:	0.014
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.013	CYP1A2-substrate:	0.896
CYP2C19-inhibitor:	0.912	CYP2C19-substrate:	0.987
CYP2C9-inhibitor:	0.961	CYP2C9-substrate:	0.088
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.94
CYP3A4-inhibitor:	0.575	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.96 ? 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):

6.519

Half-life (T1/2):

0.682

ADMET: Toxicity

hERG Blockers:	0.137	hERG Blockers (10um):	0.286
Human Hepatotoxicity (H-HT):	0.62	Drug-induced Liver Injury (DILI):	0.687
AMES Toxicity:	0.057	Rat Oral Acute Toxicity:	0.098
Maximum Recommended Daily Dose:	0.608	Skin Sensitization:	1.0
Carcinogencity:	0.142	Eye Corrosion:	0.065
Eye Irritation:	0.965	Respiratory Toxicity:	0.583
Drug-induced Neurotoxicity:	0.072	Ototoxicity:	0.421
Hematotoxicity:	0.298	Drug-induced Nephrotoxicity:	0.752
Genotoxicity:	0.017	RPMI-8226 Immunitoxicity:	0.036
A549 Cytotoxicity:	0.013	Hek293 Cytotoxicity:	0.07
BCF:	1.844 ? 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:	4.945 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.19 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.841 ? 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	=	32.5	ug.mL-1	PMID[24387625]

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	=	3.125	ug.mL-1	PMID[26067904]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	6.25	ug.mL-1	PubChem BioAssay data set
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	3.125	ug.mL-1	PMID[15217281]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	3.125	ug.mL-1	PMID[16989518]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[10978195]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	=	6.25	ug.mL-1	PMID[16643028]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	6.25	ug.mL-1	PMID[16643028]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	12.5	ug.mL-1	PMID[16643028]

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 NPC75557 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	8536
0.1-0.2	38771
0.2-0.3	2402
0.3-0.4	95
0.4-0.5	20
0.5-0.6	18
0.6-0.7	7
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC71274
0.7969	Intermediate Similarity	NPC474136
0.7846	Intermediate Similarity	NPC476351
0.7846	Intermediate Similarity	NPC283284
0.7846	Intermediate Similarity	NPC289911
0.7612	Intermediate Similarity	NPC474279
0.7361	Intermediate Similarity	NPC261733
0.7361	Intermediate Similarity	NPC307346
0.7361	Intermediate Similarity	NPC489598
0.6447	Remote Similarity	NPC14650
0.6234	Remote Similarity	NPC288209
0.6111	Remote Similarity	NPC329922
0.6111	Remote Similarity	NPC81912
0.6111	Remote Similarity	NPC329694
0.6111	Remote Similarity	NPC474260
0.6111	Remote Similarity	NPC611156
0.5974	Remote Similarity	NPC489596
0.5915	Remote Similarity	NPC474425
0.5915	Remote Similarity	NPC474426
0.5769	Remote Similarity	NPC489595
0.5647	Remote Similarity	NPC487126
0.5625	Remote Similarity	NPC267004
0.5625	Remote Similarity	NPC489597
0.5625	Remote Similarity	NPC218712
0.5588	Remote Similarity	NPC475739
0.5541	Remote Similarity	NPC474830
0.5507	Remote Similarity	NPC475706
0.5455	Remote Similarity	NPC476016
0.5362	Remote Similarity	NPC144745
0.5263	Remote Similarity	NPC131801
0.5217	Remote Similarity	NPC474424
0.52	Remote Similarity	NPC474817
0.52	Remote Similarity	NPC474829
0.5068	Remote Similarity	NPC475714

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC75557 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2925
0.1-0.2	6144
0.2-0.3	81
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