NPASS Compound

Natural Product: NPC84038

Natural Product ID	NPC84038
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Homoancepsenolide
IUPAC Name	(2S)-2-methyl-4-[14-[(2S)-2-methyl-5-oxo-2H-furan-4-yl]tetradecyl]-2H-furan-5-one
Synonyms	Homoancepsenolide
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL484441
PubChem CID	10318257
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 66 67 0 0 0 0 0 0 0 0999 V2000 -9.5596 2.4876 0.2791 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3902 1.8839 1.0500 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8082 0.7400 0.3536 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4724 0.9090 0.3019 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5666 -0.0610 -0.3319 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6037 -0.7974 0.5022 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6803 0.0661 1.2815 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6767 -0.7772 2.0551 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8593 -1.6043 1.1395 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1128 -0.7085 0.1695 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2620 -1.5229 -0.7808 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7619 -2.3413 -0.0365 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6226 -3.1565 -0.9749 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3808 -2.3082 -1.9463 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2997 -1.3486 -1.2069 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0750 -0.4831 -2.1439 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9538 0.4471 -1.3626 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9266 -0.3035 -0.5134 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7684 0.6746 0.2235 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8475 0.7638 1.5295 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7882 1.8578 1.8432 C 0 0 2 0 0 0 0 0 0 0 0 0 7.0209 2.9321 2.6083 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2202 2.3635 0.6166 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6228 1.6705 -0.4208 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7485 1.8195 -1.6703 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1699 2.2113 0.8726 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0227 2.7680 1.0082 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3687 2.7810 1.2570 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.1880 3.0072 1.0252 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1830 3.1804 -0.4958 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1405 1.6718 -0.1494 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8367 1.4909 2.0033 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3258 -0.1390 -0.0765 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1566 -0.8432 -0.9117 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0450 0.4882 -1.1905 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9454 -1.4718 -0.1440 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0874 -1.5383 1.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3383 0.5862 2.0588 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1367 0.8071 0.7003 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1938 -1.3326 2.8467 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9936 -0.0391 2.5505 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3631 -2.3828 0.5707 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1157 -2.1604 1.7904 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5076 0.0551 0.6792 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8357 -0.1632 -0.4872 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2087 -0.8200 -1.4870 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9659 -2.1645 -1.3629 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3372 -1.6624 0.6099 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2538 -3.0811 0.6188 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9861 -3.8762 -1.4905 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3566 -3.6975 -0.3444 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7244 -1.7571 -2.6449 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9994 -2.9860 -2.5694 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9412 -1.9979 -0.5616 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7323 -0.6928 -0.5187 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3326 0.1351 -2.7033 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6374 -1.0638 -2.9058 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5424 1.1226 -2.0227 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2991 1.0846 -0.7237 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5406 -0.9291 -1.2021 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4879 -0.9934 0.2130 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3332 0.1636 2.2728 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5874 1.5004 2.5014 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6770 3.8279 2.6866 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8092 2.5511 3.6192 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0886 3.1565 2.0762 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 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 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 24 25 2 0 4 26 1 0 26 27 2 0 26 28 1 0 28 2 1 0 24 19 1 0 1 29 1 0 1 30 1 0 1 31 1 0 2 32 1 1 3 33 1 0 5 34 1 0 5 35 1 0 6 36 1 0 6 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 10 45 1 0 11 46 1 0 11 47 1 0 12 48 1 0 12 49 1 0 13 50 1 0 13 51 1 0 14 52 1 0 14 53 1 0 15 54 1 0 15 55 1 0 16 56 1 0 16 57 1 0 17 58 1 0 17 59 1 0 18 60 1 0 18 61 1 0 20 62 1 0 21 63 1 1 22 64 1 0 22 65 1 0 22 66 1 0 M END

Standard InCHIKey	WPGYLBYQMCFKCB-PMACEKPBSA-N
Standard InCHI	InChI=1S/C24H38O4/c1-19-17-21(23(25)27-19)15-13-11-9-7-5-3-4-6-8-10-12-14-16-22-18-20(2)28-24(22)26/h17-20H,3-16H2,1-2H3/t19-,20-/m0/s1
SMILES	C[C@H]1C=C(CCCCCCCCCCCCCCC2=C[C@H](C)OC2=O)C(=O)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	390.28	Volume:	431.162 ? Van der Waals volume.
Dense:	0.905	LogP:	5.603 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.702 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.516 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	12.0
TPSA:	52.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.247	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.454	Fsp³:	0.75
MCE-18:	25.143 ? 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:	0.507	Fluc inhibitor:	0.56 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.013 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.745	Promiscuous compounds:	0.31

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.031	MDCK Permeability:	-4.745
Pgp-inhibitor:	0.433	Pgp-substrate:	0.221
PAMPA:	0.004 ? 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):	0.781
20% Bioavailability (F20%):	0.984	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.995
Plasma Protein Binding (PPB):	99.804%	Volume Distribution (VD):	1.122
Fu:	0.536% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.393
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.989
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.041
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.255
CYP3A4-inhibitor:	0.004	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.905 ? 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):

4.743

Half-life (T1/2):

0.869

ADMET: Toxicity

hERG Blockers:	0.21	hERG Blockers (10um):	0.702
Human Hepatotoxicity (H-HT):	0.75	Drug-induced Liver Injury (DILI):	0.862
AMES Toxicity:	0.9	Rat Oral Acute Toxicity:	0.65
Maximum Recommended Daily Dose:	0.905	Skin Sensitization:	1.0
Carcinogencity:	0.795	Eye Corrosion:	0.101
Eye Irritation:	0.793	Respiratory Toxicity:	0.646
Drug-induced Neurotoxicity:	0.691	Ototoxicity:	0.308
Hematotoxicity:	0.204	Drug-induced Nephrotoxicity:	0.985
Genotoxicity:	0.046	RPMI-8226 Immunitoxicity:	0.14
A549 Cytotoxicity:	0.936	Hek293 Cytotoxicity:	0.232
BCF:	0.61 ? 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:	4.546 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.385 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.137 ? 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
NPO1816	Pterogorgia citrina	Species	Gorgoniidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[7911157]
NPO1816	Pterogorgia citrina	Species	Gorgoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1816	Pterogorgia citrina	Species	Gorgoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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

Activity Type	# Activity
Cell line	1

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
NPT393	Cell line	HCT-116	Homo sapiens	IC50	>	50.0	ug.mL-1	PMID[15568791]

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 NPC84038 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	21802
0.1-0.2	24628
0.2-0.3	3069
0.3-0.4	207
0.4-0.5	86
0.5-0.6	39
0.6-0.7	15
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
0.8214	Intermediate Similarity	NPC218477
0.8214	Intermediate Similarity	NPC474705
0.8214	Intermediate Similarity	NPC186531
0.697	Remote Similarity	NPC609415
0.6216	Remote Similarity	NPC73310
0.6216	Remote Similarity	NPC473529
0.6216	Remote Similarity	NPC180363
0.6216	Remote Similarity	NPC94875
0.6216	Remote Similarity	NPC11332
0.6216	Remote Similarity	NPC145914
0.6216	Remote Similarity	NPC601174
0.6216	Remote Similarity	NPC601403
0.6216	Remote Similarity	NPC603568
0.6216	Remote Similarity	NPC604330
0.6216	Remote Similarity	NPC608300
0.6216	Remote Similarity	NPC611200
0.6216	Remote Similarity	NPC611571
0.6053	Remote Similarity	NPC475947
0.575	Remote Similarity	NPC25764
0.575	Remote Similarity	NPC235809
0.575	Remote Similarity	NPC329829
0.575	Remote Similarity	NPC39279
0.575	Remote Similarity	NPC469483
0.575	Remote Similarity	NPC475159
0.575	Remote Similarity	NPC39167
0.575	Remote Similarity	NPC131002
0.575	Remote Similarity	NPC292809
0.575	Remote Similarity	NPC202055
0.575	Remote Similarity	NPC473780
0.575	Remote Similarity	NPC604521
0.575	Remote Similarity	NPC606804
0.575	Remote Similarity	NPC607425
0.575	Remote Similarity	NPC608574
0.5476	Remote Similarity	NPC488224
0.5476	Remote Similarity	NPC156804
0.5349	Remote Similarity	NPC473156
0.5349	Remote Similarity	NPC163093
0.5349	Remote Similarity	NPC144415
0.5349	Remote Similarity	NPC282815
0.5349	Remote Similarity	NPC600956
0.5349	Remote Similarity	NPC607439
0.5349	Remote Similarity	NPC608157
0.5227	Remote Similarity	NPC473671
0.5227	Remote Similarity	NPC219652
0.5227	Remote Similarity	NPC475268
0.5227	Remote Similarity	NPC473840
0.5227	Remote Similarity	NPC470400
0.5227	Remote Similarity	NPC25703
0.5227	Remote Similarity	NPC77871
0.5227	Remote Similarity	NPC9678
0.5227	Remote Similarity	NPC241360
0.5227	Remote Similarity	NPC293136
0.5227	Remote Similarity	NPC319036
0.5227	Remote Similarity	NPC605867
0.5135	Remote Similarity	NPC608138
0.5111	Remote Similarity	NPC65930
0.5111	Remote Similarity	NPC132940

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC84038 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6591
0.1-0.2	2454
0.2-0.3	102
0.3-0.4	3
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