NPASS Compound

Natural Product: NPC520864

Natural Product ID	NPC520864
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(~{E},2~{Z})-2-[(3~{R})-3-hydroxy-3-[(2~{S})-2-hydroxy-5-oxo-2~{H}-furan-3-yl]propylidene]-6-methyl-8-(2,6,6-trimethylcyclohexen-1-yl)oct-5-enal
IUPAC Name	(~{E},2~{Z})-2-[(3~{R})-3-hydroxy-3-[(2~{S})-2-hydroxy-5-oxo-2~{H}-furan-3-yl]propylidene]-6-methyl-8-(2,6,6-trimethylcyclohexen-1-yl)oct-5-enal
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 -4.3372 2.2677 0.3064 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5655 0.7908 0.0898 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8861 -0.0765 0.8722 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9858 0.4597 1.8690 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5328 0.2621 1.8032 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8200 0.8382 0.6385 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0459 0.3848 -0.7470 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1161 1.7895 0.8402 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9040 2.4611 -0.1874 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3666 2.2381 -0.0948 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8221 0.8451 -0.2317 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5756 -0.1886 0.7541 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9324 0.0320 1.8144 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5506 0.5768 -1.3282 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0787 -0.7452 -1.6164 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6100 -0.6816 -1.7469 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9739 0.1731 -2.7695 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2722 -0.3826 -0.4735 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0245 0.6912 -0.2612 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5297 0.6868 1.1006 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2733 1.5481 1.6469 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0479 -0.4456 1.7110 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2595 -1.1515 0.7881 C 0 0 2 0 0 0 0 0 0 0 0 0 6.8019 -2.4265 0.5953 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2185 -1.4985 0.6290 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6408 -2.0146 -0.6579 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7434 -2.4075 1.7373 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7319 -1.6847 0.5428 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3534 -0.8060 -0.4833 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5379 0.3509 -0.9496 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2553 2.5048 0.2484 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8025 2.5558 1.2626 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8103 2.8107 -0.5365 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1558 1.5606 2.0518 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3154 0.0185 2.8676 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1133 0.6693 2.7741 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2271 -0.8297 1.8802 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0730 0.4960 -1.3190 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9024 0.8206 -1.2539 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1419 -0.7548 -0.6860 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2380 2.0613 1.9119 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7175 3.6143 -0.0926 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5027 2.2962 -1.2151 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7824 2.6731 0.8747 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8785 2.8747 -0.8772 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9223 -1.2310 0.6601 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7486 1.4172 -2.0409 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7590 -1.0551 -2.6705 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8259 -1.5109 -0.9143 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8976 -1.7166 -2.0866 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2406 0.4191 -3.3656 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2281 1.4508 -0.9916 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2327 -1.2767 1.2116 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7567 -2.3629 0.3457 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6947 -2.6055 -0.4788 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3516 -1.2423 -1.3807 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3271 -2.7814 -1.1200 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3369 -3.3563 1.6328 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6875 -2.7096 1.5578 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9334 -2.0292 2.7395 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1108 -1.4916 1.5783 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9000 -2.7608 0.3308 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3207 -0.4283 -0.0400 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6525 -1.4276 -1.3589 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0870 0.2316 -1.9574 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2715 1.2091 -1.1052 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 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 11 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 1 0 23 24 1 0 3 25 1 0 25 26 1 0 25 27 1 0 25 28 1 0 28 29 1 0 29 30 1 0 30 2 1 0 23 18 1 0 1 31 1 0 1 32 1 0 1 33 1 0 4 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 7 38 1 0 7 39 1 0 7 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 10 44 1 0 10 45 1 0 12 46 1 0 14 47 1 0 15 48 1 0 15 49 1 0 16 50 1 6 17 51 1 0 19 52 1 0 23 53 1 1 24 54 1 0 26 55 1 0 26 56 1 0 26 57 1 0 27 58 1 0 27 59 1 0 27 60 1 0 28 61 1 0 28 62 1 0 29 63 1 0 29 64 1 0 30 65 1 0 30 66 1 0 M END

Standard InCHIKey	KESXQHZIRZKRKH-DLFGAIJRSA-N
Standard InCHI	InChI=1S/C25H36O5/c1-17(10-12-21-18(2)8-6-14-25(21,3)4)7-5-9-19(16-26)11-13-22(27)20-15-23(28)30-24(20)29/h7,11,15-16,22,24,27,29H,5-6,8-10,12-14H2,1-4H3/b17-7+,19-11-/t22-,24+/m1/s1
SMILES	CC1=C(CC/C(C)=C/CC/C(C=O)=C/C[C@@H](O)C2=CC(=O)O[C@@H]2O)C(C)(C)CCC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	416.26	Volume:	451.976 ? Van der Waals volume.
Dense:	0.921	LogP:	4.82 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.963 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.484 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	15.0
TPSA:	83.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.233	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.46	Fsp³:	0.6
MCE-18:	38.25 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.966	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.114 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.304 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.525	Promiscuous compounds:	0.071

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.717	MDCK Permeability:	-4.748
Pgp-inhibitor:	0.379	Pgp-substrate:	0.709
PAMPA:	0.11 ? 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):	0.0
20% Bioavailability (F20%):	0.007	30% Bioavailability (F30%):	0.036
50% Bioavailability (F50%):	0.808

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.994
Plasma Protein Binding (PPB):	96.723%	Volume Distribution (VD):	0.064
Fu:	2.793% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.647
OATP1B3 inhibitor:	0.151	BCRP inhibitor:	0.009
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.459
CYP2C19-inhibitor:	0.696	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.623	CYP2C9-substrate:	0.076
CYP2D6-inhibitor:	0.585	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.036	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.597
HLM stability:	0.866 ? 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):

5.374

Half-life (T1/2):

0.782

ADMET: Toxicity

hERG Blockers:	0.051	hERG Blockers (10um):	0.437
Human Hepatotoxicity (H-HT):	0.918	Drug-induced Liver Injury (DILI):	0.842
AMES Toxicity:	0.788	Rat Oral Acute Toxicity:	0.806
Maximum Recommended Daily Dose:	0.977	Skin Sensitization:	0.999
Carcinogencity:	0.89	Eye Corrosion:	0.0
Eye Irritation:	0.173	Respiratory Toxicity:	0.923
Drug-induced Neurotoxicity:	0.889	Ototoxicity:	0.512
Hematotoxicity:	0.89	Drug-induced Nephrotoxicity:	0.988
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.275
A549 Cytotoxicity:	0.785	Hek293 Cytotoxicity:	0.54
BCF:	1.748 ? 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:	4.904 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.593 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.007 ? 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
NPO5099	Luffariella variabilis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0040-4039(00)77766-5]
NPO5099	Luffariella variabilis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5099	Luffariella variabilis	Species	Thorectidae	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

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

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 NPC520864 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	18551
0.1-0.2	28818
0.2-0.3	2392
0.3-0.4	64
0.4-0.5	25
0.5-0.6	5
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
0.7857	Intermediate Similarity	NPC323251
0.7069	Intermediate Similarity	NPC211892
0.6545	Remote Similarity	NPC473756
0.6	Remote Similarity	NPC262747
0.5968	Remote Similarity	NPC471298
0.5781	Remote Similarity	NPC474865
0.5714	Remote Similarity	NPC324170
0.5625	Remote Similarity	NPC126518
0.5323	Remote Similarity	NPC471297

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC520864 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7128
0.1-0.2	1990
0.2-0.3	31
0.3-0.4	0
0.4-0.5	0
0.5-0.6	1
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
0.5625	Remote Similarity	NPD6400	Clinical (unspecified phase)

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