NPASS Compound

Natural Product: NPC483457

Natural Product ID	NPC483457
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IYWKCXXBLCNUEK-FQEAUJLESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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 56 57 0 0 0 0 0 0 0 0999 V2000 -1.2798 -0.7290 -1.7513 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9013 -0.3223 -0.5172 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2081 0.1867 0.4290 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1430 0.4695 0.5562 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2112 1.0191 1.8732 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4757 0.5355 0.1570 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1274 0.0691 -1.0977 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5867 0.7204 -2.3423 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1896 -1.4083 -1.1393 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4672 -2.1101 -0.9815 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3966 -1.4089 -0.1006 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2617 -2.0099 0.7715 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1324 -1.2691 1.5400 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1207 0.1035 1.4179 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2636 0.7564 0.5503 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2644 2.2394 0.4263 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4046 -0.0085 -0.2046 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5246 0.6049 -1.0870 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0034 -1.9275 2.4215 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4078 -0.5123 -0.4060 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9818 -0.0313 0.8805 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4330 -0.3089 0.8571 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4177 0.5236 0.8842 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8141 -0.0767 0.8503 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3256 1.9708 0.9227 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1113 2.5705 0.9306 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1588 0.1128 -2.4982 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4906 -1.4549 -1.7195 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0887 -1.3256 -2.3145 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8889 0.4320 1.3366 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1414 -0.0076 0.9710 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9611 1.5949 0.4040 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3058 1.3791 -2.8733 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1624 0.0111 -3.0713 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7596 1.4240 -2.0409 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7792 -1.7121 -2.1521 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4667 -1.8409 -0.4064 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9702 -2.1167 -2.0034 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2699 -3.1604 -0.6626 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2291 -3.1053 0.8285 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7984 0.6855 2.0157 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6362 2.4467 -0.6204 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2289 2.6111 0.4610 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9654 2.7238 1.0983 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7381 -2.8285 2.8155 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6518 -1.5515 -0.6174 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8417 0.1182 -1.2339 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5414 -0.6703 1.7234 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7292 1.0002 1.1351 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6722 -1.3970 0.8101 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0378 -0.3345 -0.2018 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5199 0.6478 1.2953 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8463 -0.9941 1.4721 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9063 2.4094 0.0596 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9193 2.3518 1.8158 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8120 2.9043 0.0483 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 2 0 4 6 1 0 7 6 1 1 7 8 1 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 13 19 1 0 2 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 23 25 1 0 25 26 1 0 18 7 1 0 17 11 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 6 31 1 0 6 32 1 0 8 33 1 0 8 34 1 0 8 35 1 0 9 36 1 0 9 37 1 0 10 38 1 0 10 39 1 0 12 40 1 0 14 41 1 0 16 42 1 0 16 43 1 0 16 44 1 0 19 45 1 0 20 46 1 0 20 47 1 0 21 48 1 0 21 49 1 0 22 50 1 0 24 51 1 0 24 52 1 0 24 53 1 0 25 54 1 0 25 55 1 0 26 56 1 0 M END

Standard InCHIKey	IYWKCXXBLCNUEK-FQEAUJLESA-N
Standard InCHI	InChI=1S/C22H30O4/c1-15(6-5-7-16(2)14-23)10-20(25)13-22(4)9-8-18-12-19(24)11-17(3)21(18)26-22/h7,10-12,23-24H,5-6,8-9,13-14H2,1-4H3/b15-10+,16-7-/t22-/m0/s1
SMILES	C/C(=CC(=O)C[C@]1(C)CCc2cc(cc(C)c2O1)O)/CC/C=C(/C)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	358.21	Volume:	391.297 ? Van der Waals volume.
Dense:	0.915	LogP:	4.081 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.615 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.615 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	14.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.56	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.696	Fsp³:	0.5
MCE-18:	50.909 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.441	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.058 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.422 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.391	Promiscuous compounds:	0.007

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.127	MDCK Permeability:	-4.9
Pgp-inhibitor:	0.306	Pgp-substrate:	0.05
PAMPA:	0.098 ? 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):	0.002
20% Bioavailability (F20%):	0.282	30% Bioavailability (F30%):	0.093
50% Bioavailability (F50%):	0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.738	MRP1:	0.994
Plasma Protein Binding (PPB):	88.69%	Volume Distribution (VD):	0.034
Fu:	12.687% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.904	BCRP inhibitor:	0.01
BSEP inhibitor:	0.996

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.109
CYP2C19-inhibitor:	0.449	CYP2C19-substrate:	0.015
CYP2C9-inhibitor:	0.336	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.088	CYP2D6-substrate:	0.142
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.993
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.982
HLM stability:	0.125 ? 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):

5.719

Half-life (T1/2):

0.833

ADMET: Toxicity

hERG Blockers:	0.146	hERG Blockers (10um):	0.366
Human Hepatotoxicity (H-HT):	0.64	Drug-induced Liver Injury (DILI):	0.02
AMES Toxicity:	0.255	Rat Oral Acute Toxicity:	0.046
Maximum Recommended Daily Dose:	0.341	Skin Sensitization:	0.965
Carcinogencity:	0.361	Eye Corrosion:	0.065
Eye Irritation:	0.976	Respiratory Toxicity:	0.717
Drug-induced Neurotoxicity:	0.346	Ototoxicity:	0.328
Hematotoxicity:	0.119	Drug-induced Nephrotoxicity:	0.266
Genotoxicity:	0.012	RPMI-8226 Immunitoxicity:	0.062
A549 Cytotoxicity:	0.055	Hek293 Cytotoxicity:	0.285
BCF:	2.08 ? 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:	4.826 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.252 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.592 ? 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
NPO40176	Koeberlinia spinosa	Species	Koeberliniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29048892]

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	2

Activity Type	# Activity
Cell line	1
Organism	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
NPT179	Cell line	A2780	Homo sapiens	IC50	>	10000.0	nM	PMID[29048892]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	24000.0	nM	PMID[29048892]

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 NPC483457 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	12331
0.1-0.2	34855
0.2-0.3	2557
0.3-0.4	62
0.4-0.5	19
0.5-0.6	18
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC483459
1.0	High Similarity	NPC483456
1.0	High Similarity	NPC483458
0.7581	Intermediate Similarity	NPC32152
0.75	Intermediate Similarity	NPC483460
0.6567	Remote Similarity	NPC483462
0.6471	Remote Similarity	NPC610467
0.6406	Remote Similarity	NPC69539
0.6338	Remote Similarity	NPC59654
0.6286	Remote Similarity	NPC611336
0.6269	Remote Similarity	NPC147896
0.6197	Remote Similarity	NPC609807
0.6111	Remote Similarity	NPC271832
0.6111	Remote Similarity	NPC600119
0.6111	Remote Similarity	NPC601388
0.5972	Remote Similarity	NPC474131
0.5833	Remote Similarity	NPC232295
0.5797	Remote Similarity	NPC606596
0.5753	Remote Similarity	NPC204535
0.5753	Remote Similarity	NPC46586
0.5753	Remote Similarity	NPC185634
0.5733	Remote Similarity	NPC610755
0.5616	Remote Similarity	NPC483461
0.5526	Remote Similarity	NPC603704
0.5455	Remote Similarity	NPC474246
0.5455	Remote Similarity	NPC474130
0.5405	Remote Similarity	NPC276962
0.5405	Remote Similarity	NPC190086
0.5395	Remote Similarity	NPC196621
0.5385	Remote Similarity	NPC474143
0.5385	Remote Similarity	NPC609153
0.5325	Remote Similarity	NPC474237
0.5256	Remote Similarity	NPC475880

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC483457 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4056
0.1-0.2	5065
0.2-0.3	28
0.3-0.4	0
0.4-0.5	1
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