NPASS Compound

Natural Product: NPC218477

Natural Product ID	NPC218477
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S)-4-Dodec-11-Enyl-2-Methyl-2H-Furan-5-One
IUPAC Name	(2S)-4-dodec-11-enyl-2-methyl-2H-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL477914
PubChem CID	10801599
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002518] Annonaceous acetogenins

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 47 47 0 0 0 0 0 0 0 0999 V2000 -5.1871 1.9566 2.1076 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2364 0.6574 1.8828 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1746 0.0394 1.0225 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7319 -0.6096 -0.1779 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7439 -1.2610 -1.0526 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7086 -0.5374 -1.7801 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6740 0.2647 -1.1186 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8167 -0.4280 -0.1097 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0396 -1.5850 -0.6755 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8905 -1.1882 -1.7786 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9212 -0.1769 -1.3434 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7736 -0.7167 -0.2328 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8028 0.2794 0.2032 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1100 0.1517 0.1890 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7509 1.3698 0.7042 C 0 0 1 0 0 0 0 0 0 0 0 0 4.7049 2.2300 1.0248 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5097 1.6013 0.7338 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3534 2.1068 0.9065 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4729 0.9617 1.9891 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9586 2.4113 2.7337 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4371 2.6164 1.7184 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0053 0.0272 2.2909 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4516 0.7960 0.7986 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6302 -0.7566 1.6153 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5669 -1.3289 0.0694 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2253 0.2307 -0.7815 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3696 -1.8174 -1.8489 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2960 -2.1107 -0.4147 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2707 0.1958 -2.4754 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2497 -1.2225 -2.5913 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9892 0.6276 -1.9867 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0416 1.2108 -0.7312 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4176 -0.7902 0.7213 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0887 0.3052 0.2817 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7660 -2.3632 -0.9803 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5593 -2.0270 0.1448 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3695 -0.8085 -2.6750 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4566 -2.1064 -2.0736 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4609 0.8023 -1.0918 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6088 -0.0419 -2.2297 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1544 -0.8954 0.6760 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2285 -1.6605 -0.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6307 -0.7533 -0.1650 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4732 1.8126 -0.0187 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3035 1.6660 2.2176 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8421 -0.0698 1.8448 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6990 0.9343 2.7834 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 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 15 19 1 0 17 13 1 0 1 20 1 0 1 21 1 0 2 22 1 0 3 23 1 0 3 24 1 0 4 25 1 0 4 26 1 0 5 27 1 0 5 28 1 0 6 29 1 0 6 30 1 0 7 31 1 0 7 32 1 0 8 33 1 0 8 34 1 0 9 35 1 0 9 36 1 0 10 37 1 0 10 38 1 0 11 39 1 0 11 40 1 0 12 41 1 0 12 42 1 0 14 43 1 0 15 44 1 6 19 45 1 0 19 46 1 0 19 47 1 0 M END

Standard InCHIKey	BWPRZTNWIXWGLA-HNNXBMFYSA-N
Standard InCHI	InChI=1S/C17H28O2/c1-3-4-5-6-7-8-9-10-11-12-13-16-14-15(2)19-17(16)18/h3,14-15H,1,4-13H2,2H3/t15-/m0/s1
SMILES	C=CCCCCCCCCCCC1=C[C@@H](OC1=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	264.21	Volume:	303.703 ? Van der Waals volume.
Dense:	0.87	LogP:	5.168 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.738 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.154 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	7.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.3	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.022	Fsp³:	0.706
MCE-18:	12.414 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.328	Fluc inhibitor:	0.586 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.028 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.991	Promiscuous compounds:	0.251

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.002	MDCK Permeability:	-4.732
Pgp-inhibitor:	0.553	Pgp-substrate:	0.011
PAMPA:	0.003 ? 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):	0.15
20% Bioavailability (F20%):	0.729	30% Bioavailability (F30%):	0.944
50% Bioavailability (F50%):	0.82

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.063	MRP1:	0.937
Plasma Protein Binding (PPB):	99.178%	Volume Distribution (VD):	0.532
Fu:	0.525% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.965
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.801
BSEP inhibitor:	0.843

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.891
CYP2C9-inhibitor:	0.461	CYP2C9-substrate:	0.191
CYP2D6-inhibitor:	0.165	CYP2D6-substrate:	0.523
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.614 ? 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):

5.306

Half-life (T1/2):

0.474

ADMET: Toxicity

hERG Blockers:	0.133	hERG Blockers (10um):	0.736
Human Hepatotoxicity (H-HT):	0.464	Drug-induced Liver Injury (DILI):	0.466
AMES Toxicity:	0.849	Rat Oral Acute Toxicity:	0.63
Maximum Recommended Daily Dose:	0.8	Skin Sensitization:	1.0
Carcinogencity:	0.807	Eye Corrosion:	0.843
Eye Irritation:	0.971	Respiratory Toxicity:	0.66
Drug-induced Neurotoxicity:	0.744	Ototoxicity:	0.167
Hematotoxicity:	0.152	Drug-induced Nephrotoxicity:	0.638
Genotoxicity:	0.073	RPMI-8226 Immunitoxicity:	0.078
A549 Cytotoxicity:	0.736	Hek293 Cytotoxicity:	0.132
BCF:	1.497 ? 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:	4.562 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.936 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.962 ? 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
NPO32807	Hortonia	Genus	Monimiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11277762]

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

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

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
-	Aedes aegypti	LC50	=	0.47	ppm	DOI[10.1016/S0960-894X(01)80354-1]

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 NPC218477 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	22661
0.1-0.2	23987
0.2-0.3	2860
0.3-0.4	245
0.4-0.5	67
0.5-0.6	32
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8214	Intermediate Similarity	NPC84038
0.8065	Intermediate Similarity	NPC474705
0.697	Remote Similarity	NPC186531
0.6111	Remote Similarity	NPC210303
0.6053	Remote Similarity	NPC609415
0.5909	Remote Similarity	NPC488224
0.5476	Remote Similarity	NPC73310
0.5476	Remote Similarity	NPC473529
0.5476	Remote Similarity	NPC180363
0.5476	Remote Similarity	NPC94875
0.5476	Remote Similarity	NPC11332
0.5476	Remote Similarity	NPC145914
0.5476	Remote Similarity	NPC601174
0.5476	Remote Similarity	NPC601403
0.5476	Remote Similarity	NPC603568
0.5476	Remote Similarity	NPC604330
0.5476	Remote Similarity	NPC608300
0.5476	Remote Similarity	NPC611200
0.5476	Remote Similarity	NPC611571
0.5455	Remote Similarity	NPC469483
0.5435	Remote Similarity	NPC607439
0.5349	Remote Similarity	NPC475947
0.5111	Remote Similarity	NPC25764
0.5111	Remote Similarity	NPC235809
0.5111	Remote Similarity	NPC329829
0.5111	Remote Similarity	NPC39279
0.5111	Remote Similarity	NPC475159
0.5111	Remote Similarity	NPC39167
0.5111	Remote Similarity	NPC131002
0.5111	Remote Similarity	NPC292809
0.5111	Remote Similarity	NPC202055
0.5111	Remote Similarity	NPC473780
0.5111	Remote Similarity	NPC604521
0.5111	Remote Similarity	NPC606804
0.5111	Remote Similarity	NPC607425
0.5111	Remote Similarity	NPC608574
0.5102	Remote Similarity	NPC600188

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC218477 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6883
0.1-0.2	2197
0.2-0.3	69
0.3-0.4	1
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