NPASS Compound

Natural Product: NPC199316

Natural Product ID	NPC199316
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lubimin
IUPAC Name	(3R,5S,6R,8S,10S)-8-hydroxy-6-methyl-3-prop-1-en-2-ylspiro[4.5]decane-10-carbaldehyde
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2270658
PubChem CID	442383
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001550] Sesquiterpenoids

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 41 42 0 0 0 0 0 0 0 0999 V2000 -3.1880 -1.3687 -2.0300 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7691 -0.9045 -0.9827 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6789 0.0724 -0.9842 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1511 1.3420 -0.3588 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1035 1.3965 1.1135 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3879 1.7782 1.5730 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7182 0.1669 1.8276 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7006 -0.6959 1.1826 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.4465 -0.3957 -0.2648 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2092 -1.5734 -0.9611 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5128 -1.0100 -1.5512 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8605 -0.0336 -0.4310 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5750 0.7407 -0.3294 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0360 0.7663 -0.7034 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9590 2.0641 -0.8462 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3547 0.1055 -0.8237 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1282 -2.1496 1.3815 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2477 -1.2566 -0.0760 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3771 0.3015 -2.0285 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1846 1.5411 -0.7705 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5334 2.1813 -0.7964 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4369 2.2432 1.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7699 2.4814 0.9902 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3122 0.4675 2.8396 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6543 -0.4098 2.0888 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3037 -0.6082 1.6946 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5746 -2.3338 -0.2093 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4162 -2.0264 -1.7312 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2677 -1.7829 -1.6908 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2497 -0.5018 -2.4779 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0452 -0.6539 0.4701 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4550 1.3249 -1.2637 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6058 1.3349 0.5817 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0028 2.5539 -0.7603 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8250 2.6722 -1.0491 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0612 0.6773 -1.4589 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8247 0.0609 0.1858 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2646 -0.9575 -1.1624 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3728 -2.7476 1.8983 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0644 -2.2238 1.9725 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3461 -2.6387 0.4066 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 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 6 10 11 1 0 11 12 1 0 12 13 1 0 12 14 1 0 14 15 2 0 14 16 1 0 8 17 1 0 9 3 1 0 13 9 1 0 2 18 1 0 3 19 1 6 4 20 1 0 4 21 1 0 5 22 1 6 6 23 1 0 7 24 1 0 7 25 1 0 8 26 1 1 10 27 1 0 10 28 1 0 11 29 1 0 11 30 1 0 12 31 1 1 13 32 1 0 13 33 1 0 15 34 1 0 15 35 1 0 16 36 1 0 16 37 1 0 16 38 1 0 17 39 1 0 17 40 1 0 17 41 1 0 M END

Standard InCHIKey	CEVNHRPKRNTGKO-ZSAUSMIDSA-N
Standard InCHI	InChI=1S/C15H24O2/c1-10(2)12-4-5-15(8-12)11(3)6-14(17)7-13(15)9-16/h9,11-14,17H,1,4-8H2,2-3H3/t11-,12-,13-,14+,15+/m1/s1
SMILES	O=C[C@H]1C[C@@H](O)C[C@H]([C@]21CC[C@H](C2)C(=C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	236.18	Volume:	263.191 ? Van der Waals volume.
Dense:	0.897	LogP:	2.392 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.147 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.912 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	13.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.591	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.988	Fsp³:	0.8
MCE-18:	52.37 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.429	Fluc inhibitor:	0.0 ? 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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.93	Promiscuous compounds:	0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.994	MDCK Permeability:	-4.794
Pgp-inhibitor:	0.12	Pgp-substrate:	0.138
PAMPA:	0.096 ? 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):	0.005
20% Bioavailability (F20%):	0.291	30% Bioavailability (F30%):	0.222
50% Bioavailability (F50%):	0.544

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.934	MRP1:	0.835
Plasma Protein Binding (PPB):	81.628%	Volume Distribution (VD):	0.224
Fu:	19.656% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.306
OATP1B3 inhibitor:	0.578	BCRP inhibitor:	0.222
BSEP inhibitor:	0.572

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.065
CYP2C19-inhibitor:	0.019	CYP2C19-substrate:	0.127
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.129
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.944
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.817
HLM stability:	0.503 ? 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):

8.993

Half-life (T1/2):

1.792

ADMET: Toxicity

hERG Blockers:	0.077	hERG Blockers (10um):	0.29
Human Hepatotoxicity (H-HT):	0.396	Drug-induced Liver Injury (DILI):	0.244
AMES Toxicity:	0.882	Rat Oral Acute Toxicity:	0.602
Maximum Recommended Daily Dose:	0.608	Skin Sensitization:	0.995
Carcinogencity:	0.785	Eye Corrosion:	0.554
Eye Irritation:	0.882	Respiratory Toxicity:	0.814
Drug-induced Neurotoxicity:	0.838	Ototoxicity:	0.317
Hematotoxicity:	0.594	Drug-induced Nephrotoxicity:	0.783
Genotoxicity:	0.841	RPMI-8226 Immunitoxicity:	0.114
A549 Cytotoxicity:	0.782	Hek293 Cytotoxicity:	0.568
BCF:	0.809 ? 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:	3.356 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.92 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.395 ? 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
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/0168-1656(92)90069-L]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/S0031-9422(00)89267-5]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	root	n.a.	DOI[10.1271/bbb1961.42.623]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12882150]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15374592]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15666542]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	Roots	n.a.	n.a.	PMID[31742403]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39527985]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	trunk bark	n.a.	PMID[556731]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	Tubers	n.a.		Database[FooDB]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	Tuber	n.a.	n.a.	Database[FooDB]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7732	Solanum melongena	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6495	Datura stramonium	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4359	Solanum tuberosum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25348	Metapochonia suchlasporia	Species	Clavicipitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16093	Achillea atrata	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

Activity Type	# Activity
Activity	2

Activity Type	# Activity
Organism	2

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
NPT1503	Organism	Verticillium dahliae	Verticillium dahliae	Activity	=	42.0	%	PMID[11577721]
NPT1200	Organism	Fusarium oxysporum f. sp. melongenae	Fusarium oxysporum f. sp. melongenae	Activity	=	5.0	%	PMID[11577721]

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 NPC199316 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	18811
0.1-0.2	27758
0.2-0.3	3259
0.3-0.4	29
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC102313

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC199316 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6402
0.1-0.2	2681
0.2-0.3	67
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