NPASS Compound

Natural Product: NPC476351

Natural Product ID	NPC476351
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(5Z)-5-[(2R,5Z,10Z)-13-(Furan-3-Yl)-2,6,11-Trimethyltrideca-5,10-Dienylidene]-4-Hydroxy-3-Methylfuran-2-One
IUPAC Name	(5Z)-5-[(2R,5Z,10Z)-13-(furan-3-yl)-2,6,11-trimethyltrideca-5,10-dienylidene]-4-hydroxy-3-methylfuran-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL574762
PubChem CID	54736252
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001983] Dihydrofurans [CHEMONTID:0001982] Furanones [CHEMONTID:0002223] Butenolides

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 0.3220 2.4610 0.0838 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1105 1.0301 -0.1139 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3231 0.8860 -0.6356 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9515 -0.4315 -0.9187 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2029 -0.6473 -0.1193 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2776 0.3799 -0.3532 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4277 0.0034 0.5201 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6459 -0.2334 0.0748 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0754 -0.1824 -1.2251 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.4237 -0.4979 -1.2643 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1782 -0.5559 -2.2940 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.8811 -0.7660 0.0918 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8302 -0.6086 0.8753 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8307 -0.7695 2.2417 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.2760 -1.1446 0.4958 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6638 0.4810 -1.8044 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7272 -0.1067 0.2969 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0162 -0.2917 -0.4055 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9884 0.8593 -0.2889 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2307 0.5320 -0.9961 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4333 0.4922 -0.4741 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6628 0.7886 0.9400 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1963 -0.3096 1.8009 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4960 -0.8074 1.3578 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7339 -0.2528 1.6651 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6425 -0.9979 1.1305 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1250 -2.0112 0.4865 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7569 -1.9313 0.6040 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6197 0.1849 -1.3776 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0905 2.5863 0.8428 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5166 2.8989 -0.9046 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5646 3.0561 0.4707 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8769 1.8184 -0.8645 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3014 -0.3700 -1.9996 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2759 -1.2851 -0.8764 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9962 -0.6918 0.9721 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6312 -1.6325 -0.4675 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9361 1.3806 -0.0032 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3026 -0.0944 1.5991 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3991 -0.1287 2.8067 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5469 -0.6651 1.4596 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3213 -2.2343 0.5053 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.0138 -0.7757 -0.2462 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4630 1.2688 -1.9141 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7912 0.8658 -2.3986 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9977 -0.4761 -2.2335 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2038 -1.0838 0.3340 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9531 0.1036 1.4114 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8776 -0.5889 -1.4773 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5502 -1.1781 0.0433 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1239 1.0468 0.7827 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5622 1.7733 -0.7770 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1654 0.2943 -2.0684 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8535 1.3679 1.4459 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5196 1.5805 0.9661 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2457 0.1047 2.8450 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4998 -1.1886 1.8373 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9049 0.6576 2.2577 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7300 -2.7642 -0.0390 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0717 -2.6389 0.1696 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5280 0.4673 -0.8683 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6189 -0.8374 -1.7323 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5501 0.8874 -2.2734 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 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 12 15 1 0 6 16 1 0 2 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 27 28 2 0 21 29 1 0 13 8 1 0 28 24 1 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 1 7 39 1 0 14 40 1 0 15 41 1 0 15 42 1 0 15 43 1 0 16 44 1 0 16 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 19 52 1 0 20 53 1 0 22 54 1 0 22 55 1 0 23 56 1 0 23 57 1 0 25 58 1 0 27 59 1 0 28 60 1 0 29 61 1 0 29 62 1 0 29 63 1 0 M END

Standard InCHIKey	KLKIESMJEUHQLI-KLURGBKRSA-N
Standard InCHI	InChI=1S/C25H34O4/c1-18(8-5-6-9-19(2)12-13-22-14-15-28-17-22)10-7-11-20(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/1OC(=O)C(=C1O)C)C)/CCC/C=C(CCc1cocc1)/C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	398.25	Volume:	440.549 ? Van der Waals volume.
Dense:	0.904	LogP:	7.111 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.295 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.387 ? 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:	0.248	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.87	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:	0.979	Fluc inhibitor:	0.28 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.023 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.343 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.434	Promiscuous compounds:	0.055

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.091	MDCK Permeability:	-4.78
Pgp-inhibitor:	0.911	Pgp-substrate:	0.0
PAMPA:	0.001 ? 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):	0.038
20% Bioavailability (F20%):	0.768	30% Bioavailability (F30%):	0.938
50% Bioavailability (F50%):	0.889

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.041	MRP1:	0.996
Plasma Protein Binding (PPB):	97.636%	Volume Distribution (VD):	0.004
Fu:	2.297% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.091
OATP1B3 inhibitor:	0.185	BCRP inhibitor:	0.025
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.096	CYP1A2-substrate:	0.746
CYP2C19-inhibitor:	0.057	CYP2C19-substrate:	0.967
CYP2C9-inhibitor:	0.532	CYP2C9-substrate:	0.063
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.384	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.984 ? 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):

6.316

Half-life (T1/2):

0.745

ADMET: Toxicity

hERG Blockers:	0.153	hERG Blockers (10um):	0.274
Human Hepatotoxicity (H-HT):	0.602	Drug-induced Liver Injury (DILI):	0.469
AMES Toxicity:	0.093	Rat Oral Acute Toxicity:	0.152
Maximum Recommended Daily Dose:	0.656	Skin Sensitization:	1.0
Carcinogencity:	0.136	Eye Corrosion:	0.143
Eye Irritation:	0.972	Respiratory Toxicity:	0.637
Drug-induced Neurotoxicity:	0.074	Ototoxicity:	0.405
Hematotoxicity:	0.257	Drug-induced Nephrotoxicity:	0.745
Genotoxicity:	0.022	RPMI-8226 Immunitoxicity:	0.036
A549 Cytotoxicity:	0.024	Hek293 Cytotoxicity:	0.092
BCF:	1.856 ? 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:	4.878 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.096 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.704 ? 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
NPO32965	smenospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497955]
NPO32965	smenospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[16252912]
NPO32965	smenospongia sp.	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18973387]

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	6

Activity Type	# Activity
Individual protein	1
Organism	6

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4391	Individual protein	Isocitrate lyase	Magnaporthe oryzae (strain 70-15 / FGSC 8958) (Rice blast fungus)(Pyricularia oryzae)	IC50	=	31.2	ug.mL-1	DOI[10.1021/np960649a]

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	=	3.12	ug.mL-1	PMID[20194700]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	12.5	ug.mL-1	PMID[20643902]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	6.25	ug.mL-1	PMID[18636777]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	6.25	ug.mL-1	PMID[19555124]
NPT766	Organism	Proteus vulgaris	Proteus vulgaris	MIC	=	6.25	ug.mL-1	PubChem BioAssay data set
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[17896816]

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 NPC476351 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	8188
0.1-0.2	39381
0.2-0.3	2135
0.3-0.4	105
0.4-0.5	21
0.5-0.6	16
0.6-0.7	6
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8281	Intermediate Similarity	NPC474136
0.7846	Intermediate Similarity	NPC71274
0.7846	Intermediate Similarity	NPC75557
0.7612	Intermediate Similarity	NPC283284
0.7612	Intermediate Similarity	NPC289911
0.7391	Intermediate Similarity	NPC474279
0.6711	Remote Similarity	NPC14650
0.6282	Remote Similarity	NPC261733
0.6282	Remote Similarity	NPC307346
0.6282	Remote Similarity	NPC489598
0.6282	Remote Similarity	NPC288209
0.6234	Remote Similarity	NPC489596
0.5875	Remote Similarity	NPC267004
0.5875	Remote Similarity	NPC489597
0.5875	Remote Similarity	NPC218712
0.5823	Remote Similarity	NPC489595
0.5698	Remote Similarity	NPC487126
0.5429	Remote Similarity	NPC475739
0.5352	Remote Similarity	NPC475706
0.5128	Remote Similarity	NPC329922
0.5128	Remote Similarity	NPC81912
0.5128	Remote Similarity	NPC329694
0.5128	Remote Similarity	NPC474260
0.5128	Remote Similarity	NPC611156
0.5122	Remote Similarity	NPC215109
0.5122	Remote Similarity	NPC170604
0.507	Remote Similarity	NPC474424
0.5065	Remote Similarity	NPC474817

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476351 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2987
0.1-0.2	6095
0.2-0.3	68
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