NPASS Compound

Natural Product: NPC511962

Natural Product ID	NPC511962
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-[2-[(1~{S},3~{S},4~{a}~{R},8~{a}~{R})-3-hydroxy-5,5,8~{a}-trimethyl-2-methylene-decalin-1-yl]ethyl]-2~{H}-furan-5-one
IUPAC Name	4-[2-[(1~{S},3~{S},4~{a}~{R},8~{a}~{R})-3-hydroxy-5,5,8~{a}-trimethyl-2-methylene-decalin-1-yl]ethyl]-2~{H}-furan-5-one
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 53 55 0 0 0 0 0 0 0 0999 V2000 0.9808 2.1132 2.1374 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0608 1.7229 1.3062 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4702 0.8648 0.0983 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9107 0.6357 0.1072 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6150 -0.0647 -0.9819 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0828 -0.1708 -0.7309 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0184 0.3209 -1.4992 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3463 0.0177 -0.9282 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1031 -0.7060 0.2605 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7282 -0.8246 0.3872 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1131 -1.3997 1.3102 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4984 -0.3231 0.1725 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4704 -0.8982 1.5893 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1743 -1.3436 -0.8307 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2757 -2.4008 -0.8837 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6031 -1.8611 -1.2367 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9528 -0.5735 -0.5681 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0496 -0.8874 0.4629 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7069 0.2655 -1.6230 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8651 0.2426 -0.0421 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2916 0.9452 1.2670 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3426 2.0837 1.5149 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6317 3.1908 0.7204 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7108 2.7428 3.0308 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0442 1.9197 2.1174 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1849 1.4962 -0.7648 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3943 1.6817 0.2093 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1790 0.2110 1.1238 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2378 -0.9872 -1.3993 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5371 0.6485 -1.8886 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9127 0.8787 -2.4304 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8997 0.9361 -0.6320 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9790 -0.6062 -1.5704 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3614 -1.4833 1.7981 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3938 -1.6237 1.6564 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3192 -0.1354 2.3421 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6983 -1.9978 -0.5042 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0432 -0.8977 -1.8248 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9120 -3.1601 -1.6056 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2615 -2.8922 0.1111 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3600 -2.6492 -1.0305 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6313 -1.7543 -2.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6790 -1.0282 1.4704 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8170 -0.0896 0.4934 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5927 -1.8174 0.1700 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7558 -0.0382 -1.6915 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7052 1.3428 -1.3095 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2550 0.1228 -2.6255 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6917 1.1502 -0.7239 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2956 1.4287 1.1044 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2751 0.2895 2.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4958 2.3980 2.5746 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2873 2.9644 0.0200 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 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 3 12 1 0 12 13 1 1 12 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 17 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 22 2 1 0 10 6 1 0 20 12 1 0 1 24 1 0 1 25 1 0 3 26 1 6 4 27 1 0 4 28 1 0 5 29 1 0 5 30 1 0 7 31 1 0 8 32 1 0 8 33 1 0 13 34 1 0 13 35 1 0 13 36 1 0 14 37 1 0 14 38 1 0 15 39 1 0 15 40 1 0 16 41 1 0 16 42 1 0 18 43 1 0 18 44 1 0 18 45 1 0 19 46 1 0 19 47 1 0 19 48 1 0 20 49 1 6 21 50 1 0 21 51 1 0 22 52 1 1 23 53 1 0 M END

Standard InCHIKey	FTEOKKHVMZMVFW-YZLZLFLDSA-N
Standard InCHI	InChI=1S/C20H30O3/c1-13-15(7-6-14-8-11-23-18(14)22)20(4)10-5-9-19(2,3)17(20)12-16(13)21/h8,15-17,21H,1,5-7,9-12H2,2-4H3/t15-,16+,17-,20+/m1/s1
SMILES	C=C1[C@@H](CCC2=CCOC2=O)[C@]2(C)CCCC(C)(C)[C@H]2C[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.22	Volume:	347.268 ? Van der Waals volume.
Dense:	0.916	LogP:	3.619 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.581 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.303 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.631	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.478	Fsp³:	0.75
MCE-18:	54.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.531	Fluc inhibitor:	0.3 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.684	Promiscuous compounds:	0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.69	MDCK Permeability:	-4.696
Pgp-inhibitor:	0.241	Pgp-substrate:	0.078
PAMPA:	0.339 ? 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%):	0.025	30% Bioavailability (F30%):	0.017
50% Bioavailability (F50%):	0.65

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.545	MRP1:	0.45
Plasma Protein Binding (PPB):	98.858%	Volume Distribution (VD):	0.106
Fu:	2.035% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.988
OATP1B3 inhibitor:	0.966	BCRP inhibitor:	0.049
BSEP inhibitor:	0.691

ADMET: Metabolism

CYP1A2-inhibitor:	0.059	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.462	CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.044	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.019	CYP2D6-substrate:	0.073
CYP3A4-inhibitor:	0.447	CYP3A4-substrate:	0.146
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.328
HLM stability:	0.549 ? 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):

10.866

Half-life (T1/2):

0.984

ADMET: Toxicity

hERG Blockers:	0.094	hERG Blockers (10um):	0.594
Human Hepatotoxicity (H-HT):	0.562	Drug-induced Liver Injury (DILI):	0.285
AMES Toxicity:	0.69	Rat Oral Acute Toxicity:	0.863
Maximum Recommended Daily Dose:	0.9	Skin Sensitization:	0.999
Carcinogencity:	0.935	Eye Corrosion:	0.056
Eye Irritation:	0.47	Respiratory Toxicity:	0.826
Drug-induced Neurotoxicity:	0.581	Ototoxicity:	0.339
Hematotoxicity:	0.536	Drug-induced Nephrotoxicity:	0.897
Genotoxicity:	0.728	RPMI-8226 Immunitoxicity:	0.184
A549 Cytotoxicity:	0.623	Hek293 Cytotoxicity:	0.578
BCF:	2.125 ? 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:	4.901 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.456 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.045 ? 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
NPO3569	Acritopappus morii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3569	Acritopappus morii	Species	Asteraceae	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 NPC511962 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	15901
0.1-0.2	26999
0.2-0.3	6320
0.3-0.4	520
0.4-0.5	88
0.5-0.6	19
0.6-0.7	9
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
0.7018	Intermediate Similarity	NPC234993
0.7018	Intermediate Similarity	NPC134072
0.6607	Remote Similarity	NPC50488
0.6607	Remote Similarity	NPC474396
0.6545	Remote Similarity	NPC106416
0.6545	Remote Similarity	NPC86316
0.6545	Remote Similarity	NPC609165
0.6491	Remote Similarity	NPC177037
0.6491	Remote Similarity	NPC472814
0.6429	Remote Similarity	NPC182136
0.6034	Remote Similarity	NPC329692
0.569	Remote Similarity	NPC608380
0.5593	Remote Similarity	NPC200513
0.5424	Remote Similarity	NPC251528
0.541	Remote Similarity	NPC311070
0.541	Remote Similarity	NPC139692
0.5352	Remote Similarity	NPC392
0.5352	Remote Similarity	NPC177524
0.5352	Remote Similarity	NPC219900
0.5246	Remote Similarity	NPC79027
0.5246	Remote Similarity	NPC51486
0.5179	Remote Similarity	NPC306727
0.5167	Remote Similarity	NPC12170
0.5161	Remote Similarity	NPC472809
0.5161	Remote Similarity	NPC472810
0.5161	Remote Similarity	NPC475709
0.5085	Remote Similarity	NPC4509
0.5082	Remote Similarity	NPC29952
0.507	Remote Similarity	NPC479457
0.5068	Remote Similarity	NPC479461

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC511962 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6287
0.1-0.2	2689
0.2-0.3	168
0.3-0.4	3
0.4-0.5	1
0.5-0.6	2
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
0.5593	Remote Similarity	NPD4752	Clinical (unspecified phase)
0.5352	Remote Similarity	NPD6686	Approved

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